JP7478150B2 - Urinary catheters, bladder catheters, systems, kits and methods for inducing negative pressure and increasing renal function - Patents.com - Google Patents

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of U.S. Provisional Application No. 62/300,025, filed February 25, 2016, U.S. Provisional Application No. 62/278,721, filed January 14, 2016, U.S. Provisional Application No. 62/260,966, filed November 30, 2015, and U.S. Provisional Application No. 62/194,585, filed July 20, 2015, each of which is incorporated herein by reference in its entirety. This application claims priority from U.S. patent application Ser. No. 16/205,987, filed Nov. 30, 2018, which is a continuation-in-part of U.S. patent application Ser. No. 15/411,884, filed Jan. 20, 2017, which is a continuation-in-part of U.S. patent application Ser. No. 15/687,064, filed Aug. 25, 2017, which is a continuation-in-part of U.S. patent application Ser. No. 15/879,770, filed Jan. 25, 2018.

Also, U.S. Provisional Application No. 62/300,025, filed February 25, 2016, U.S. Provisional Application No. 62/278,721, filed January 14, 2016, and U.S. Provisional Application No. 62/260,966, filed November 30, 2015, each of which is incorporated herein by reference in its entirety, U.S. Patent Application No. 15/879,770, filed January 25, 2018. , which claims the benefit of U.S. Provisional Application No. 62/194,585, filed July 20, 2015, which is a continuation-in-part of U.S. Patent Application No. 15/214,955, filed July 20, 2016, which is a continuation-in-part of U.S. Patent Application No. 15/411,884, filed January 20, 2017, which is a continuation-in-part of U.S. Patent Application No. 15/687,083, filed August 25, 2017.

Also, U.S. Patent Application No. 15/879,770, filed January 25, 2018, each of which is incorporated herein by reference in its entirety.
This is a continuation-in-part of U.S. Provisional Application No. 15/745,823, filed January 18, 2018, which is the U.S. national stage of PCT/US2016/043101, filed July 20, 2016, which claims the benefit of U.S. Provisional Application No. 62/300,025, filed February 25, 2016, U.S. Provisional Application No. 62/278,721, filed January 14, 2016, U.S. Provisional Application No. 62/260,966, filed November 30, 2015, and U.S. Provisional Application No. 62/194,585, filed July 20, 2015.

U.S. Patent Application No. 15/879,770, filed January 25, 2018, also claims the benefit of U.S. Provisional Application No. 62/489,789, filed April 25, 2017, and U.S. Provisional Application No. 62/489,831, filed April 25, 2017.

The present disclosure relates to methods and devices for treating renal dysfunction across a variety of medical conditions, and in particular to methods for removing fluid (e.g., urine) from a patient by applying negative pressure through a ureteral catheter, a ureteral stent, and/or a bladder catheter, for example, by using a ureteral stent, a ureteral catheter, and/or a bladder catheter, or a combination of a ureteral stent and/or a ureteral catheter and a bladder catheter.

The renal or urinary system includes a pair of kidneys, each connected by a ureter to the bladder and a urethra for draining fluid or urine produced by the kidney from the bladder. The kidneys perform several important functions for the human body, including, for example, filtering blood and eliminating waste products in the form of urine. The kidneys also regulate electrolytes (e.g., sodium, potassium, and calcium) and metabolites, blood volume, blood pressure, blood pH, body fluid volume, red blood cell production, and bone metabolism. A proper understanding of renal anatomy and physiology is useful for understanding the effects of altered hemodynamics and other volume overload conditions on its function.

In normal anatomy, the two kidneys are located retroperitoneally within the abdominal cavity. The kidneys are bean-shaped encapsulated organs. Urine is formed by the nephron, the functional unit of the kidney, and then flows through a system of converging tubules called collecting ducts. The collecting ducts join together to form the minor and then major calyces, and finally join near the concave part of the kidney (the renal pelvis). The main function of the renal pelvis is to direct urine flow to the ureters. From the renal pelvis, urine flows into the ureters, which are tubular structures that carry urine from the kidneys into the bladder. The outer layer of the kidney is called the cortex, a rigid fibrous capsule. The interior of the kidney is called the medulla. The medullary structures are arranged in a pyramidal shape.

Each kidney consists of approximately one million nephrocytes. Each nephrocyte contains a glomerulus, a Bowman's capsule, and a tubule. The tubule contains a proximal convoluted tubule, a loop of Henle, a distal convoluted tubule, and a collecting duct. The nephrocytes contained within the outer cortical layer of the kidney have a distinctly different anatomy from those contained within the medulla. The main difference is the length of the loop of Henle. Medullary nephrocytes contain longer loops of Henle, which allows for better regulation of water and sodium reabsorption than outer cortical nephrocytes under normal circumstances.

The glomerulus is the origin of the renal unit and is responsible for the initial filtration of blood. The afferent arteriole passes blood into the glomerular capillaries, where hydrostatic pressure pushes water and solutes into Bowman's capsule. Net filtration pressure is expressed as the hydrostatic pressure in the afferent arteriole minus the hydrostatic pressure in Bowman's space minus the osmotic pressure in the efferent arteriole.
Net filtration pressure = hydrostatic pressure (afferent arteriole) - hydrostatic pressure (Bowman's space) - osmotic pressure (efferent arteriole) (Equation 1)

The magnitude of this net filtration pressure, defined by Equation 1, determines the amount of ultrafiltrate that is formed in the Bowman's space and delivered to the renal tubule. The remaining blood leaves the glomerulus via the efferent arteriole. Normal glomerular filtration, i.e., delivery of ultrafiltrate into the renal tubule, is approximately 90 ml/min/1.73 ^m2 .

The glomerulus has a three-layer filtration structure, including the vascular endothelium, the glomerular basement membrane, and the podocytes. Normally, large proteins such as albumin and red blood cells are not filtered into Bowman's space. However, elevated glomerular pressure and mesangial expansion result in surface area changes on the basement membrane, and larger fenestrations between podocytes allow larger proteins to pass into Bowman's space.

The ultrafiltrate collected in the Bowman's space is first delivered to the proximal convoluted tubule. Reabsorption and secretion of water and solutes within the tubule is carried out by a mixture of active transport channels and passive pressure gradients. The proximal convoluted tubule normally reabsorbs most of the sodium chloride and water, and nearly all of the glucose and amino acids filtered by the glomerulus. The loop of Henle has two components designed to concentrate waste products in urine. The descending limb is highly water permeable and reabsorbs most of the remaining water. The ascending limb reabsorbs 25% of the remaining sodium chloride, producing a concentrated urine, e.g., in terms of urea and creatinine. The distal convoluted tubule normally reabsorbs a small percentage of sodium chloride, and the osmotic gradient results in a state where water follows.

Under normal conditions, net filtration is about 14 mmHg. The effects of venous stasis can result in a significant decrease in net filtration to about 4 mmHg. See Jessup M., The cardiorenal syndrome: Do we need a change of strategy or a change of tactics?, JACC 53(7):597-600, 2009 (hereafter "Jessup"). The second filtration step occurs in the proximal tubule. The majority of secretion and absorption from urine occurs in tubules within the medullary renal unit. Active transport of sodium from the tubule into the interstitial space begins the process. However, hydrostatic forces govern the net exchange of solutes and water. Under normal circumstances, it is believed that 75% of sodium is reabsorbed into the lymphatic or venous circulation. However, because the kidneys are encapsulated, they are sensitive to changes in hydrostatic pressure from both venous and lymphatic congestion. During venous congestion, sodium and water retention can exceed 85%, further prolonging renal congestion. Verbrugge et al., The kidney in congestive heart failure: Are natriuresis, sodium, and diruetucs really the good, the bad and the ugly? See European Journal of Heart Failure 2014:16,133-42 (hereafter "Verbrugge").

Venous congestion can lead to prerenal forms of acute kidney injury (AKI). Prerenal AKI results from loss of perfusion (or loss of blood flow) through the kidney. Many clinicians focus on the lack of flow into the kidney due to the acute circulatory failure state. However, there is evidence that lack of blood flow from the organ due to venous congestion can also be a clinically significant lasting injury. See Damman K, Importance of venous congestion for worsening renal function in advanced decompensated heart failure, JACC 17:589-96,2009 (hereafter "Damman").

Prerenal AKI occurs across a variety of diagnoses and requires critical care hospitalization. The most prominent hospitalizations are for sepsis and acute decompensated heart failure (ADHF). Additional hospitalizations include cardiovascular surgery, general surgery, cirrhosis, trauma, burns, and pancreatitis. The symptoms of these disease states have wide clinical variation, but a common denominator is elevated central venous pressure. In ADHF, elevated central venous pressure caused by heart failure leads to pulmonary edema and subsequent dyspnea, which in turn prompts hospitalization. In sepsis, elevated central venous pressure is primarily the result of massive fluid resuscitation. Whether the primary insult is hypovolemia or hypoperfusion due to sodium and fluid retention, the persistent insult is venous stasis resulting in inadequate perfusion.

Hypertension is another widely recognized condition that results in perturbations within the active and passive transport systems of the kidney. Hypertension directly affects afferent arteriolar pressure, resulting in a proportional increase in net filtration pressure within the glomerulus. The increased filtration rate also elevates peritubular capillary pressure, which stimulates sodium and water reabsorption. See Verbrugge.

Because the kidney is an encapsulated organ, it is sensitive to pressure changes within the medullary pyramids. Increased renal venous pressure results in stasis leading to increased interstitial pressure. Increased interstitial pressure exerts forces on both the glomerulus and tubule. See Verbrugge. In the glomerulus, increased interstitial pressure directly opposes filtration. Increased pressure increases interstitial fluid, thereby increasing hydrostatic pressure in the interstitial fluid and peritubular capillaries within the renal medulla. In both cases, hypoxia can ensure cell injury and further loss of perfusion. The net result is further deterioration of sodium and water reabsorption, resulting in negative feedback. See Verbrugge (133-42). In particular, intraperitoneal fluid volume overload is associated with many diseases and conditions, including elevated intraperitoneal pressure, abdominal compartment syndrome, and acute renal failure. Fluid volume overload can be addressed through renal replacement therapy. Peters, C. D. , Short and Long-Term Effects of the Angiotensin II Receptor Blocker Irbesartanon Intradialytic Central Hemodynamics: A Randomized Double-Blind Placebo-Controlled One-Year Intervention Trial (SAFIR Study), PLoS ONE (2015) 10 (6): e0126882. doi:10.1371/journal. Pone. See Peters, J. Neurosci. 2012; 367:2296-2304 (hereinafter "Bart"). However, such clinical strategies do not provide improvement in renal function in patients with cardiorenal syndrome. See Bart B, Ultrafiltration in decompensated heart failure with cardiorenal syndrome, NEJM 2012; 367:2296-2304 (hereinafter "Bart").

In light of such problematic effects of fluid retention, systems and methods are needed to improve the removal of fluids, such as urine, from a patient, and specifically, to increase the quantity and quality of fluid output from the kidneys.

In some embodiments, a ureteral or bladder catheter is provided, the catheter comprising: (a) a proximal portion; and (b) a distal portion, the distal portion comprising a retention portion having one or more protected drainage holes, ports, or perforations, the retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure through the catheter.

In some embodiments, a system for inducing negative pressure within a portion of a patient's urinary tract is provided, the system comprising: (a) a ureteral catheter having a distal portion for insertion within the patient's kidney and a proximal portion; (b) a bladder catheter having a distal portion for insertion within the patient's bladder and a proximal portion for application of negative pressure, the proximal portion extending outside the patient's body; and (c) a pump that is external to the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, thus drawing fluid from the kidney into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body.

In some embodiments, a kit for inducing negative pressure within a portion of a patient's urinary tract is provided, the kit comprising one or two ureteral catheters, each ureteral catheter comprising (a) a proximal portion and (b) a distal portion, the distal portion comprising one or more protected drains, ports, or perforations, the distal portion comprising a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drains, ports, or perforations in response to application of negative pressure through the catheter, and a pump that is external to the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, thus drawing fluid from the kidney into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body.

In some embodiments, a kit is provided that includes a plurality of disposable bladder catheters, each having (a) a proximal portion and (b) a distal portion, the distal portion including one or more protected drains, ports, or perforations, the distal portion including a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drains, ports, or perforations in response to application of negative pressure through the catheter; instructions for deploying the bladder catheter; and instructions for connecting the proximal end of the bladder catheter to a pump and for operating the pump to draw urine through the drainage lumen of the bladder catheter.

In some embodiments, a method is provided for inducing negative pressure within a portion of a patient's urinary tract, the method including the steps of: deploying a ureteral catheter within the patient's ureter to maintain patency of fluid flow between the patient's kidney and bladder, the ureteral catheter having a distal portion for insertion within the patient's kidney and a proximal portion; deploying a bladder catheter within the patient's bladder, the bladder catheter having a distal portion for insertion within the patient's bladder and a proximal portion for application of negative pressure, the proximal portion extending outside the patient's body; and applying negative pressure to a proximal end of the bladder catheter to induce negative pressure within the portion of the patient's urinary tract and remove fluid from the patient.

Non-limiting examples, aspects, or embodiments of the present invention will now be described in the appended claims numbered below.

Appendix 1. A ureteral catheter comprising: (a) a proximal portion; and (b) a distal portion comprising one or more protected drainage holes, ports, or perforations, the distal portion comprising a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure through the catheter.

Appendix 2. The ureteral catheter of appendix 1, wherein one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion, and an outer periphery or protected surface area of the retention portion of the catheter is configured to support mucosal tissue, thereby preventing occlusion of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the ureteral catheter.

Appendix 3. A ureteral catheter according to any of appendices 1 or 2, wherein the retention portion comprises one or more helical coils, each coil having an outwardly facing side and an inwardly facing side, an outer periphery or protected surface area comprises the outwardly facing side of the one or more helical coils, and one or more protected drain holes, ports, or perforations are disposed on the inwardly facing side of the one or more helical coils.

Appendix 4. The ureteral catheter of any of appendices 1-3, wherein the retention portion is configured as a funnel-shaped support having an outer surface and an inner surface, the outer periphery or protective surface area comprises the outer surface of the funnel-shaped support, and the one or more drainage holes, ports, or perforations are disposed on the inner surface of the funnel-shaped support.

Appendix 5. A ureteral catheter according to any one of appendices 1-4, wherein the retention portion is configured to extend to a deployed position in which the diameter of the retention portion exceeds the diameter of the drainage lumen portion.

Appendix 6. A ureteral catheter according to any one of appendices 1-5, in which the number of drainage holes, ports, or perforations towards the distal end of the retention portion exceeds the number of drainage holes, ports, or perforations towards the proximal end of the retention portion.

Appendix 7. A ureteral catheter according to any of appendices 1-6, in which the size of one or more of the drainage holes, ports, or perforations toward the distal end of the retention portion is greater than the size of one or more of the drainage holes, ports, or perforations toward the proximal end of the retention portion.

Appendix 8. A ureteral catheter according to any one of appendices 1-7, in which the total area of the drainage holes, ports, or perforations toward the distal end of the retention portion is greater than the total area of the drainage holes, ports, or perforations toward the proximal end of the retention portion.

Appendix 9. A ureteral catheter according to any one of appendices 1-8, wherein the sidewall of the proximal portion of the ureteral catheter is essentially free of or has no drainage openings.

Appendix 10. A bladder catheter comprising: (a) a proximal portion; and (b) a distal portion comprising one or more protected drains, ports, or perforations, the distal portion comprising a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drains, ports, or perforations in response to application of negative pressure through the catheter.

Appendix 11. The bladder catheter of appendix 10, wherein one or more protected drain holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion, and an outer periphery or protected surface area of the retention portion of the catheter is configured to support mucosal tissue, thereby preventing occlusion of one or more of the protected drain holes, ports, or perforations in response to application of negative pressure through the bladder catheter.

Appendix 12. A bladder catheter as described in appendix 10 or 11, wherein the retention portion comprises one or more helical coils, each coil having an outwardly facing side and an inwardly facing side, an outer periphery or protected surface area comprises the outwardly facing side of the one or more helical coils, and one or more protected drain holes, ports, or perforations are disposed on the inwardly facing side of the one or more helical coils.

Appendix 13. A bladder catheter according to any of appendices 10-12, wherein the retention portion is configured as a funnel-shaped support having an outer surface and an inner surface, the outer periphery or protective surface area comprises the outer surface of the funnel-shaped support, and one or more drainage holes, ports, or perforations are disposed on the inner surface of the funnel-shaped support.

Appendix 14. A bladder catheter according to any one of appendices 10-13, wherein the retention portion is configured to extend to a deployed position in which the diameter of the retention portion exceeds the diameter of the drainage lumen portion.

Appendix 15. A bladder catheter according to any of appendices 10-14, in which the number of drainage holes, ports, or perforations toward the distal end of the retention portion exceeds the number of drainage holes, ports, or perforations toward the proximal end of the retention portion.

Appendix 16. A bladder catheter according to any of appendices 10-15, in which the size of one or more of the drain holes, ports, or perforations toward the distal end of the retention portion is greater than the size of one or more of the drain holes, ports, or perforations toward the proximal end of the retention portion.

Appendix 17. A bladder catheter according to any of appendices 10-16, in which the total area of the drainage holes, ports, or perforations toward the distal end of the retention portion is greater than the total area of the drainage holes, ports, or perforations toward the proximal end of the retention portion.

Appendix 18. A bladder catheter according to any of appendices 10-17, wherein the sidewall of the proximal portion of the ureteral catheter is essentially free of or has no drainage openings.

Appendix 19. A system for inducing negative pressure within a portion of a patient's urinary tract, comprising: (a) at least one ureteral catheter having a distal portion configured for insertion within the patient's kidney and a proximal portion; and (b) a bladder catheter having a distal portion configured for insertion within the patient's bladder and a proximal portion configured to transmit negative pressure into the kidney, thus causing fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body.

Appendix 20. The system of Appendix 19, wherein the distal portion of the ureteral catheter includes one or more protected drainage holes, ports, or perforations, and includes a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure.

Appendix 21. The system of appendix 20, wherein one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retained portion of the ureteral catheter, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the retained portion of the ureteral catheter, thereby preventing or inhibiting occlusion of one or more of the protected drainage holes, ports, or perforations.

Appendix 22. The system of any of Appendices 19-21, wherein the proximal portion of the ureteral catheter is in fluid communication with the distal portion of the bladder catheter.

Appendix 23. The system of any of Appendices 19-22, wherein the distal portion of the bladder catheter includes one or more protected drainage holes, ports, or perforations, and includes a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure.

Appendix 24. The system of appendix 23, wherein one or more protected drain holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the bladder catheter, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the retention portion of the bladder catheter, thereby preventing or inhibiting occlusion of one or more of the protected drain holes, ports, or perforations.

Appendix 25. The system of any of appendices 19-24, further comprising a negative pressure source for application of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body.

Appendix 26. The system of appendix 25, wherein the negative pressure source comprises a vacuum source external to the patient's body for application and adjustment of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body.

Appendix 27. The system of appendix 25 or 26, wherein the negative pressure received from the negative pressure source is controlled manually, automatically, or a combination thereof.

Appendix 28. A system according to any one of appendices 25-27, wherein the controller is used to regulate the negative pressure from the negative pressure source.

Appendix 29. The system of Appendix 28, wherein the controller provides an accuracy of about 10 mmHg or less.

Appendix 30. A system according to any one of appendices 25-29, wherein the negative pressure is provided within a range of about 2 mmHg to about 150 mmHg.

Appendix 31. The system of any of Appendices 19-30, further comprising one or more physiological sensors configured to detect at least one physical parameter of the patient.

Appendix 32. The system of appendix 31, wherein the at least one physical parameter comprises one or more of collected urine volume, urine composition, urine protein concentration, blood composition, or blood flow.

Appendix 33. The system of appendix 32, wherein at least one physical parameter of blood composition comprises one or more of a hematocrit ratio, an analyte concentration, a protein concentration, or a creatinine concentration.

Appendix 34. The system of appendix 32, wherein at least one physical parameter of blood flow comprises one or more of blood pressure or blood flow velocity.

Additional Note 35. The system of Additional Note 31, wherein the one or more physiological sensors include one or more of a pulse oximetry sensor, a blood pressure sensor, a heart rate sensor, a respiration sensor, a capnography sensor, a glucose sensor, a blood rate sensor, a hemoglobin sensor, a hematocrit sensor, a protein sensor, a creatinine sensor, an analyte sensor, a capacitance sensor, an optical spectroscopy sensor, or a combination thereof.

Appendix 36. A system for inducing negative pressure within a portion of a patient's urinary tract, comprising: (a) a ureteral catheter having a distal portion configured for insertion within the patient's kidney and a proximal portion; (b) a bladder catheter having a distal portion configured for insertion within the patient's bladder and a proximal portion for application of negative pressure, the proximal portion extending outside the patient's body; and (c) a pump that is external to the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, thus drawing fluid from the kidney into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body.

Appendix 37. The system of appendix 36, wherein the proximal portion of the ureteral catheter is in fluid communication with the distal portion of the bladder catheter.

Note 38. The system of any one of notes 36 and 37, wherein the distal portion of the ureteral catheter includes one or more protected drainage holes, ports, or perforations, and includes a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure by the pump.

Appendix 39. The system of appendix 38, wherein one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retained portion of the ureteral catheter, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the retained portion of the catheter, thereby preventing or inhibiting occlusion of one or more of the protected drainage holes, ports, or perforations.

Appendix 40. The system of any of Appendices 36-39, wherein the distal portion of the bladder catheter includes one or more protected drainage holes, ports, or perforations, and includes a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure by the pump.

Appendix 41. The system of appendix 40, wherein one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the retention portion of the catheter, thereby preventing or inhibiting occlusion of one or more of the protected drainage holes, ports, or perforations.

Appendix 42. The system of any of Appendices 36-41, further comprising one or more physiological sensors configured to detect at least one physical parameter of the patient.

Appendix 43. The system of appendix 42, wherein the at least one physical parameter comprises one or more of collected urine volume, urine composition, urine protein concentration, blood composition, or blood flow.

Appendix 44. The system of appendix 43, wherein at least one physical parameter of blood composition comprises one or more of a hematocrit ratio, an analyte concentration, a protein concentration, or a creatinine concentration.

Appendix 45. The system of appendix 43, wherein at least one physical parameter of blood flow comprises one or more of blood pressure or blood flow velocity.

Additional Note 46. The system of Additional Note 42, wherein the one or more physiological sensors include one or more of a pulse oximetry sensor, a blood pressure sensor, a heart rate sensor, a respiration sensor, a capnography sensor, a glucose sensor, a blood rate sensor, a hemoglobin sensor, a hematocrit sensor, a protein sensor, a creatinine sensor, an analyte sensor, a capacitance sensor, an optical spectroscopy sensor, or a combination thereof.

Appendix 47. The system of any of Appendices 36-46, wherein the pump provides an accuracy of about 10 mmHg or less.

Appendix 48. A system according to any one of appendices 36-47, wherein the negative pressure is provided within a range of about 2 mmHg to about 150 mmHg.

Appendix 49. A system for inducing negative pressure within a portion of a patient's urinary tract, comprising: (a) at least one ureteral catheter, the at least one ureteral catheter comprising a distal portion for insertion within the patient's kidney and a proximal portion; (b) a bladder catheter comprising a distal portion for insertion within the patient's bladder and a proximal portion for receiving negative pressure from a negative pressure source, at least one of the at least one ureteral catheter or bladder catheter comprising: (a) a proximal portion; (b) a distal portion comprising one or more protected drains, ports, or perforations, the distal portion comprising a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drains, ports, or perforations in response to application of negative pressure through the catheter; and (c) a negative pressure source for application of negative pressure through both the bladder catheter and the ureteral catheter, thus drawing fluid from the kidney into the ureteral catheter, then through the bladder catheter, and then outside the patient's body.

Appendix 50. The system of appendix 49, wherein a proximal portion of at least one ureteral catheter is in fluid communication with a distal portion of the bladder catheter.

Note 51. The system of note 49, wherein the distal portion of at least one ureteral catheter includes one or more protected drainage holes, ports, or perforations, and includes a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure from a negative pressure source.

Appendix 52. The system of appendix 51, wherein one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the ureteral catheter, and an outer periphery or protected surface area of the retention portion of the ureteral catheter is configured to support mucosal tissue, thereby preventing occlusion of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the ureteral catheter.

Note 53. The system of note 49, wherein the distal portion of the bladder catheter includes a retention portion that includes one or more protected drainage holes, ports, or perforations and is configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure from a negative pressure source.

Appendix 54. The system of appendix 53, wherein one or more protected drain holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the bladder catheter, and an outer periphery or protected surface area of the retention portion of the bladder catheter is configured to support mucosal tissue, thereby preventing occlusion of one or more of the protected drain holes, ports, or perforations in response to application of negative pressure through the bladder catheter.

Appendix 55. The system of appendix 49, further comprising one or more physiological sensors associated with the patient, the physiological sensors configured to provide information representative of at least one physical parameter to the controller.

Appendix 56. The system of appendix 49, wherein the negative pressure source includes a pump external to the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body.

Appendix 57. The system of appendix 49, wherein the negative pressure source comprises a vacuum source external to the patient's body for application and adjustment of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body.

Appendix 58. The system of appendix 57, wherein the vacuum source is selected from the group consisting of a wall suction source, a vacuum bottle, and a manual vacuum source.

Appendix 59. The system of appendix 57, wherein the vacuum source is provided by a pressure differential.

Appendix 60. A system as described in any of appendices 49-59, wherein the negative pressure received from the negative pressure source is controlled manually, automatically, or a combination thereof.

Appendix 61. A system according to any of appendices 49-60, wherein the controller is used to regulate the negative pressure from the negative pressure source.

Appendix 62. The system of Appendix 56, wherein the pump provides an accuracy of about 10 mmHg or less.

Appendix 63. The system of any of Appendices 49-62, wherein the negative pressure is provided within a range of about 2 mmHg to about 150 mmHg.

Appendix 64. A system for inducing negative pressure within a portion of a patient's urinary tract, comprising: (a) at least one ureteral catheter, the at least one ureteral catheter comprising a distal portion for insertion within the patient's kidney and a proximal portion; and (b) a bladder catheter comprising a distal portion for insertion within the patient's bladder and a proximal portion for receiving negative pressure, the negative pressure causing fluid from the kidney to be drawn into the ureteral catheter, through the bladder catheter, and then outside the patient's body, at least one of the at least one ureteral or bladder catheter comprising: (a) a proximal portion; and (b) a distal portion comprising one or more protected drains, ports, or perforations, the distal portion comprising a retaining portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drains, ports, or perforations in response to application of negative pressure through the at least one ureteral or bladder catheter.

Appendix 65. The system of appendix 64, wherein the proximal portion of at least one ureteral catheter is in fluid communication with the distal portion of the bladder catheter.

Note 66. The system of note 64, wherein the distal portion of at least one ureteral catheter includes one or more protected drainage holes, ports, or perforations and includes a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of a pressure differential.

A system according to claim 66, wherein one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the ureteral catheter, and an outer periphery or protected surface area of the retention portion of the ureteral catheter is configured to support mucosal tissue, thereby preventing occlusion of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the ureteral catheter.

Note 68. The system of note 64, wherein the distal portion of the bladder catheter includes one or more protected drains, ports, or perforations, and includes a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drains, ports, or perforations in response to application of negative pressure.

A system as described in claim 68, wherein one or more protected drain holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the bladder catheter, and an outer periphery or protected surface area of the retention portion of the bladder catheter is configured to support mucosal tissue, thereby preventing occlusion of one or more of the protected drain holes, ports, or perforations in response to application of negative pressure through the bladder catheter.

Additional Note 70. The system of Additional Note 64, further comprising one or more physiological sensors associated with the patient, the physiological sensors configured to provide information representative of at least one physical parameter to the controller.

Appendix 71. A kit for inducing negative pressure in a portion of a patient's urinary tract, comprising one or two ureteral catheters as described in appendix 1, and a pump that is external to the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, thus drawing fluid from the kidney into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body.

Appendix 72. The kit of appendix 71, further comprising a bladder catheter.

Claim 73. The kit of claim 71, further comprising instructions for inserting a bladder catheter and operating the pump to withdraw urine through a drainage lumen of the catheter deployed within the patient's bladder.

Appendix 74. A kit comprising a plurality of disposable bladder catheters according to appendix 6, instructions for deploying the bladder catheters, and instructions for connecting the proximal end of the bladder catheter to a pump and for operating the pump to draw urine through the drainage lumen of the bladder catheter.

Appendix 75. A method for inducing negative pressure in a portion of a patient's urinary tract, comprising the steps of: deploying a ureteral catheter in the patient's ureter to maintain patency of fluid flow between the patient's kidney and bladder, the ureteral catheter having a distal portion for insertion into the patient's kidney and a proximal portion; deploying a bladder catheter in the patient's bladder, the bladder catheter having a distal portion for insertion into the patient's bladder and a proximal portion for application of negative pressure, the proximal portion extending outside the patient's body; and applying negative pressure to a proximal end of the bladder catheter to induce negative pressure in a portion of the patient's urinary tract and remove fluid from the patient.

Note 76. The method of note 75, wherein at least one of the ureteral or bladder catheters comprises: (a) a proximal portion; and (b) a distal portion, the distal portion comprising a retention portion having one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure through the catheter.

Appendix 77. The method of appendix 75, wherein the ureteral catheter is deployed and remains within the patient's body for at least 24 hours.

Appendix 78. The method of appendix 75, wherein the ureteral catheter is deployed and remains within the patient's body for at least 30 days or longer.

Appendix 79. The method of appendix 75, wherein the bladder catheter is replaced more frequently than the ureteral catheter.

Clause 80. The method of clause 75, wherein multiple bladder catheters are placed and removed during the indwelling time for a single set of ureteral catheters.
The present invention provides, for example, the following items.
(Item 1)
1. A ureteral catheter comprising: (a) a proximal portion; and (b) a distal portion, the distal portion comprising a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure through the catheter.
(Item 2)
2. The ureteral catheter of claim 1, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion, and an outer periphery or protected surface area of the retention portion of the catheter is configured to support the mucosal tissue, thereby preventing occlusion of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the ureteral catheter.
(Item 3)
2. The ureteral catheter of claim 1, wherein the retention portion comprises one or more helical coils, each coil having an outwardly facing side and an inwardly facing side, the outer periphery or protected surface area comprises the outwardly facing side of the one or more helical coils, and the one or more protected drain holes, ports, or perforations are disposed on the inwardly facing side of the one or more helical coils.
(Item 4)
2. The ureteral catheter of claim 1, wherein the retention portion is configured as a funnel-shaped support having an outer surface and an inner surface, the outer periphery or protective surface area comprises the outer surface of the funnel-shaped support, and the one or more drainage holes, ports, or perforations are disposed on the inner surface of the funnel-shaped support.
(Item 5)
2. The ureteral catheter of claim 1, wherein the retention portion is configured to extend to a deployed position in which a diameter of the retention portion exceeds a diameter of the drainage lumen portion.
(Item 6)
2. The ureteral catheter of claim 1, wherein the number of drainage holes, ports, or perforations toward the distal end of the retention portion exceeds the number of drainage holes, ports, or perforations toward the proximal end of the retention portion.
(Item 7)
2. The ureteral catheter of claim 1, wherein a size of one or more of the drainage holes, ports, or perforations toward a distal end of the retention portion is greater than a size of one or more of the drainage holes, ports, or perforations toward a proximal end of the retention portion.
(Item 8)
2. The ureteral catheter of claim 1, wherein a total area of the drainage holes, ports, or perforations toward a distal end of the retention portion is greater than a total area of the drainage holes, ports, or perforations toward a proximal end of the retention portion.
(Item 9)
2. The ureteral catheter of claim 1, wherein the sidewall of the proximal portion of the ureteral catheter is essentially devoid of or devoid of drainage openings.
(Item 10)
1. A bladder catheter comprising: (a) a proximal portion; and (b) a distal portion, the distal portion comprising a retention portion, the retention portion comprising one or more protected drains, ports, or perforations, and configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drains, ports, or perforations in response to application of negative pressure through the catheter.
(Item 11)
11. The bladder catheter of claim 10, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion, and an outer periphery or protected surface area of the retention portion of the catheter is configured to support the mucosal tissue, thereby preventing occlusion of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the bladder catheter.
(Item 12)
11. The bladder catheter of claim 10, wherein the retention portion comprises one or more helical coils, each coil having an outwardly facing side and an inwardly facing side, the outer periphery or protected surface area comprises the outwardly facing side of the one or more helical coils, and the one or more protected drain holes, ports, or perforations are disposed on the inwardly facing side of the one or more helical coils.
(Item 13)
Item 11. The bladder catheter of item 10, wherein the retention portion is configured into a funnel-shaped support having an outer surface and an inner surface, the outer periphery or protective surface area comprising the outer surface of the funnel-shaped support, and the one or more drainage holes, ports, or perforations are disposed on the inner surface of the funnel-shaped support.
(Item 14)
11. The bladder catheter of claim 10, wherein the retention portion is configured to extend to a deployed position in which a diameter of the retention portion exceeds a diameter of the drainage lumen portion.
(Item 15)
11. The bladder catheter of claim 10, wherein the number of drainage holes, ports, or perforations toward the distal end of the retention portion exceeds the number of drainage holes, ports, or perforations toward the proximal end of the retention portion.
(Item 16)
11. The bladder catheter of claim 10, wherein a size of one or more of the drain holes, ports, or perforations toward a distal end of the retention portion exceeds a size of one or more of the drain holes, ports, or perforations toward a proximal end of the retention portion.
(Item 17)
11. The bladder catheter of claim 10, wherein a total area of the drainage holes, ports, or perforations toward a distal end of the retention portion is greater than a total area of the drainage holes, ports, or perforations toward a proximal end of the retention portion.
(Item 18)
11. The bladder catheter of claim 10, wherein the sidewall of the proximal portion of the ureteral catheter is essentially free or devoid of drainage openings.
(Item 19)
1. A system for inducing negative pressure within a portion of a patient's urinary tract, the system comprising:
(a) at least one ureteral catheter, the at least one ureteral catheter comprising a distal portion configured for insertion within the patient's kidney, renal pelvis, and/or ureter, and a proximal portion;
(b) a bladder catheter, the bladder catheter comprising a distal portion configured for insertion into a patient's bladder and a proximal portion, the proximal portion configured to transmit negative pressure into the kidney, thus causing fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter and then outside the patient's body; and
A system comprising:
(Item 20)
20. The system of claim 19, wherein the distal portion of the ureteral catheter comprises a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure.
(Item 21)
21. The system of claim 20, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the ureteral catheter, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the retention portion of the ureteral catheter, thereby preventing or inhibiting occlusion of one or more of the protected drainage holes, ports, or perforations.
(Item 22)
20. The system of claim 19, wherein a proximal portion of the ureteral catheter is in fluid communication with a distal portion of the bladder catheter.
(Item 23)
20. The system of claim 19, wherein the distal portion of the bladder catheter comprises a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure.
(Item 24)
24. The system of claim 23, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the bladder catheter, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the retention portion of the bladder catheter, thereby preventing or inhibiting occlusion of one or more of the protected drainage holes, ports, or perforations.
(Item 25)
20. The system of claim 19, further comprising a negative pressure source for application of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body.
(Item 26)
26. The system of claim 25, wherein the negative pressure source comprises a vacuum source external to the patient's body for application and adjustment of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body.
(Item 27)
26. The system of claim 25, wherein the negative pressure received from the negative pressure source is controlled manually, automatically, or a combination thereof.
(Item 28)
26. The system of claim 25, wherein a controller is used to regulate the negative pressure from the negative pressure source.
(Item 29)
30. The system of claim 28, wherein the controller provides an accuracy of about 10 mmHg or less.
(Item 30)
26. The system of claim 25, wherein the negative pressure is provided in a range of about 2 mmHg to about 150 mmHg.
(Item 31)
20. The system of claim 19, further comprising one or more physiological sensors configured to detect at least one physical parameter of the patient.
(Item 32)
32. The system of claim 31, wherein the at least one physical parameter comprises one or more of collected urine volume, urine composition, urine protein concentration, blood composition, or blood flow.
(Item 33)
33. The system of claim 32, wherein the at least one physical parameter of blood composition comprises one or more of a hematocrit ratio, an analyte concentration, a protein concentration, or a creatinine concentration.
(Item 34)
33. The system of claim 32, wherein the at least one physical parameter of blood flow comprises one or more of blood pressure or blood flow velocity.
(Item 35)
32. The system of claim 31, wherein the one or more physiological sensors comprise one or more of a pulse oximetry sensor, a blood pressure sensor, a heart rate sensor, a respiration sensor, a capnography sensor, a glucose sensor, a blood rate sensor, a hemoglobin sensor, a hematocrit sensor, a protein sensor, a creatinine sensor, an analyte sensor, a capacitance sensor, an optical spectroscopy sensor, or a combination thereof.
(Item 36)
1. A system for inducing negative pressure within a portion of a patient's urinary tract, the system comprising:
(a) a ureteral catheter, the ureteral catheter comprising a distal portion configured for insertion within the patient's kidney, renal pelvis, and/or ureter, and a proximal portion;
(b) a bladder catheter, the bladder catheter comprising a distal portion configured for insertion within a patient's bladder and a proximal portion for application of negative pressure, the proximal portion configured to extend outside the patient's body;
(c) a pump, the pump being external to the patient's body due to the application of negative pressure through both the bladder catheter and the ureteral catheter, thus causing fluid from the kidney to be drawn into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body;
A system comprising:
(Item 37)
37. The system of claim 36, wherein a proximal portion of the ureteral catheter is in fluid communication with a distal portion of the bladder catheter.
(Item 38)
37. The system of claim 36, wherein the distal portion of the ureteral catheter comprises a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure by the pump.
(Item 39)
39. The system of claim 38, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the ureteral catheter, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the retention portion of the catheter, thereby preventing or inhibiting occlusion of one or more of the protected drainage holes, ports, or perforations.
(Item 40)
37. The system of claim 36, wherein the distal portion of the bladder catheter comprises a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure by the pump.
(Item 41)
41. The system of claim 40, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the retention portion of the catheter, thereby preventing or inhibiting occlusion of one or more of the protected drainage holes, ports, or perforations.
(Item 42)
40. The system of claim 36, further comprising one or more physiological sensors configured to detect at least one physical parameter of the patient.
(Item 43)
43. The system of claim 42, wherein the at least one physical parameter comprises one or more of collected urine volume, urine composition, urine protein concentration, blood composition, or blood flow.
(Item 44)
44. The system of claim 43, wherein the at least one physical parameter of blood composition comprises one or more of a hematocrit ratio, an analyte concentration, a protein concentration, or a creatinine concentration.
(Item 45)
44. The system of claim 43, wherein the at least one physical parameter of blood flow comprises one or more of blood pressure or blood flow velocity.
(Item 46)
43. The system of claim 42, wherein the one or more physiological sensors comprise one or more of a pulse oximetry sensor, a blood pressure sensor, a heart rate sensor, a respiration sensor, a capnography sensor, a glucose sensor, a blood rate sensor, a hemoglobin sensor, a hematocrit sensor, a protein sensor, a creatinine sensor, an analyte sensor, a capacitance sensor, an optical spectroscopy sensor, or a combination thereof.
(Item 47)
37. The system of claim 36, wherein the pump provides an accuracy of about 10 mmHg or less.
(Item 48)
Item 37. The system of item 36, wherein the negative pressure is provided in a range of about 2 mmHg to about 150 mmHg.
(Item 49)
1. A system for inducing negative pressure within a portion of a patient's urinary tract, the system comprising:
(a) at least one ureteral catheter, the at least one ureteral catheter comprising a distal portion for insertion into the patient's kidney, renal pelvis, and/or ureter, and a proximal portion;
(b) a bladder catheter comprising a distal portion for insertion into the patient's bladder and a proximal portion for receiving negative pressure from a negative pressure source, at least one of the at least one ureteral catheter or the bladder catheter comprising (a) a proximal portion and (b) a distal portion, the distal portion comprising a retention portion comprising one or more protected drains, ports, or perforations, and configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drains, ports, or perforations in response to application of negative pressure through the catheter;
(c) a negative pressure source for application of negative pressure through both the bladder catheter and the ureteral catheter, thus causing fluid from the kidney to be drawn into the ureteral catheter, then through the bladder catheter, and then outside the patient's body;
A system comprising:
(Item 50)
50. The system of claim 49, wherein a proximal portion of the at least one ureteral catheter is in fluid communication with a distal portion of the bladder catheter.
(Item 51)
50. The system of claim 49, wherein a distal portion of the at least one ureteral catheter comprises a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure from the negative pressure source.
(Item 52)
52. The system of claim 51, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the ureteral catheter, and an outer periphery or protected surface area of the retention portion of the ureteral catheter is configured to support the mucosal tissue, thereby preventing blockage of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the ureteral catheter.
(Item 53)
50. The system of claim 49, wherein the distal portion of the bladder catheter comprises a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure from the negative pressure source.
(Item 54)
54. The system of claim 53, wherein the one or more protected drain holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the bladder catheter, and an outer periphery or protected surface area of the retention portion of the bladder catheter is configured to support the mucosal tissue, thereby preventing occlusion of one or more of the protected drain holes, ports, or perforations in response to application of negative pressure through the bladder catheter.
(Item 55)
50. The system of claim 49, further comprising one or more physiological sensors associated with the patient, the physiological sensors configured to provide information representative of at least one physical parameter to the controller.
(Item 56)
50. The system of claim 49, wherein the negative pressure source comprises a pump external to the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body.
(Item 57)
50. The system of claim 49, wherein the negative pressure source comprises a vacuum source external to the patient's body for application and adjustment of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body.
(Item 58)
58. The system of claim 57, wherein the vacuum source is selected from the group consisting of a wall suction source, a vacuum bottle, and a manual vacuum source.
(Item 59)
Item 58. The system of item 57, wherein the vacuum source is provided by a pressure differential.
(Item 60)
50. The system of claim 49, wherein the negative pressure received from the negative pressure source is controlled manually, automatically, or a combination thereof.
(Item 61)
50. The system of claim 49, wherein a controller is used to regulate the negative pressure from the negative pressure source.
(Item 62)
57. The system of claim 56, wherein the pump provides an accuracy of about 10 mmHg or less.
(Item 63)
50. The system of claim 49, wherein the negative pressure is provided in a range of about 2 mmHg to about 150 mmHg.
(Item 64)
1. A system for inducing negative pressure within a portion of a patient's urinary tract, the system comprising:
(a) at least one ureteral catheter, the at least one ureteral catheter comprising a distal portion for insertion into the patient's kidney, renal pelvis, and/or ureter, and a proximal portion;
(b) a bladder catheter, the bladder catheter comprising a distal portion for insertion into the patient's bladder and a proximal portion for receiving negative pressure, the negative pressure causing fluid from the kidney to be drawn into the ureteral catheter, through the bladder catheter, and then outside the patient's body; and
Equipped with
At least one of the at least one ureteral catheter or the bladder catheter comprises (a) a proximal portion and (b) a distal portion, the distal portion comprising a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from obstructing the one or more protected drainage holes, ports, or perforations in response to application of the negative pressure through the at least one ureteral catheter or the bladder catheter.
(Item 65)
65. The system of claim 64, wherein a proximal portion of the at least one ureteral catheter is in fluid communication with a distal portion of the bladder catheter.
(Item 66)
65. The system of claim 64, wherein the distal portion of the at least one ureteral catheter comprises a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of the pressure differential.
(Item 67)
67. The system of claim 66, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the ureteral catheter, and an outer periphery or protected surface area of the retention portion of the ureteral catheter is configured to support the mucosal tissue, thereby preventing blockage of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the ureteral catheter.
(Item 68)
65. The system of claim 64, wherein the distal portion of the bladder catheter comprises a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of the negative pressure.
(Item 69)
70. The system of claim 68, wherein the one or more protected drain holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the bladder catheter, and an outer periphery or protected surface area of the retention portion of the bladder catheter is configured to support the mucosal tissue, thereby preventing blockage of one or more of the protected drain holes, ports, or perforations in response to application of negative pressure through the bladder catheter.
(Item 70)
65. The system of claim 64, further comprising one or more physiological sensors associated with the patient, the physiological sensors configured to provide information representative of at least one physical parameter to the controller.
(Item 71)
1. A kit for inducing negative pressure in a portion of a patient's urinary tract, said kit comprising:
One or two ureteral catheters according to item 1;
a pump, the pump being external to the patient's body due to the application of negative pressure through both the bladder catheter and the ureteral catheter, thus causing fluid from the kidney to be drawn into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body;
A kit comprising:
(Item 72)
72. The kit of claim 71, further comprising a bladder catheter.
(Item 73)
72. The kit of claim 71, further comprising instructions for inserting a bladder catheter and operating the pump to withdraw urine through a drainage lumen of a catheter deployed within the patient's bladder.
(Item 74)
A kit comprising:
A plurality of disposable bladder catheters according to item 6;
instructions to deploy the bladder catheter;
instructions for connecting a proximal end of the bladder catheter to a pump and for operating the pump to draw urine through a drainage lumen of the bladder catheter;
A kit comprising:
(Item 75)
1. A method for inducing negative pressure within a portion of a patient's urinary tract, the method comprising:
deploying a ureteral catheter into a kidney, renal pelvis, and/or ureter of a patient to maintain patency of fluid flow between the kidney and bladder of the patient, the ureteral catheter comprising a distal portion for insertion within the kidney or renal pelvis of the patient and a proximal portion;
deploying a bladder catheter into the patient's bladder, the bladder catheter comprising a distal portion for insertion into the patient's bladder and a proximal portion for application of negative pressure, the proximal portion extending outside the patient's body;
applying a negative pressure to a proximal end of the bladder catheter to induce negative pressure within a portion of the patient's urinary tract to remove fluid from the patient;
A method comprising:
(Item 76)
76. The method of claim 75, wherein at least one of the ureteral catheter or the bladder catheter comprises (a) a proximal portion and (b) a distal portion, the distal portion comprising a retention portion, the retention portion comprising one or more protected drainage holes, ports, or perforations, and configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure through the catheter.
(Item 77)
76. The method of claim 75, wherein the urinary catheter is deployed and remains within the patient's body for at least 24 hours.
(Item 78)
76. The method of claim 75, wherein the urinary catheter is deployed and remains within the patient's body for at least 30 days or longer.
(Item 79)
76. The method of claim 75, wherein the bladder catheter is changed more frequently than the ureteral catheter.
(Item 80)
76. The method of claim 75, wherein multiple bladder catheters are placed and removed during the residence time for a single set of ureteral catheters.

These and other features and characteristics of the present disclosure, as well as the method of operation and function of the associated elements of structure and combination of parts and economies of manufacture, will become more apparent from a consideration of the following description and the accompanying appendix, with reference to the accompanying drawings, all of which form a part of this specification and in which like reference numerals designate corresponding parts in the various views. It is to be expressly understood, however, that the drawings are for purposes of illustration and description only and are not intended as a definition of the limits of the invention.

Further features and other embodiments and advantages will become apparent from the following detailed description of the invention considered in conjunction with the drawings.

FIG. 1A is a schematic diagram of an indwelling portion of a system comprising a ureteral stent and a bladder catheter deployed within a patient's urinary tract, in accordance with an embodiment of the present invention.

FIG. 1B is a schematic diagram of an indwelling portion of the system, including a ureteral catheter and a bladder catheter deployed within a patient's urinary tract, in accordance with an embodiment of the present invention.

FIG. 1C is a schematic diagram of an indwelling portion of the system, including a ureteral catheter and a bladder catheter deployed within a patient's urinary tract, in accordance with an embodiment of the present invention.

FIG. 1D is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1E is a cross-sectional view of the retention portion of FIG. 1D taken along line 1E-1E of FIG. 1D, in accordance with an embodiment of the present invention.

FIG. 1F is a schematic diagram of an indwelling portion of a system including a ureteral catheter and a bladder catheter deployed within a patient's urinary tract, in accordance with an embodiment of the present invention.

FIG. 1G is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1H is a side elevational view of the retention portion of FIG. 1G, in accordance with an embodiment of the present invention.

FIG. 1I is a top plan view of the retention portion of FIG. 1G, according to an embodiment of the present invention.

FIG. 1J is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1K is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1L is a side elevational view of a retention portion of a bladder catheter prior to deployment, in accordance with an embodiment of the present invention.

FIG. 1M is a side elevational view of the retention portion of FIG. 1L after deployment, according to an embodiment of the present invention.

FIG. 1N is a perspective view of a retention portion of a bladder catheter, according to an embodiment of the present invention.

FIG. 1O is a cross-sectional view of a portion of the retention portion of FIG. 1N, in accordance with an embodiment of the present invention.

FIG. 1P is a schematic diagram of an indwelling portion of a system including a ureteral catheter and a bladder catheter deployed within a patient's urinary tract, in accordance with an embodiment of the present invention.

FIG. 1Q is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1R is a cross-sectional view of a portion of the retention portion of FIG. 1Q, in accordance with an embodiment of the present invention.

FIG. 1S is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1T is a cross-sectional view of a portion of the retention portion of FIG. 1S, in accordance with an embodiment of the present invention.

FIG. 1U is a schematic diagram of an indwelling portion of a system including a ureteral catheter and a bladder catheter deployed within a patient's urinary tract, in accordance with an embodiment of the present invention.

FIG. 1V is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1W is a cross-sectional view of the retention portion of FIG. 1V taken along line 1W-1W of FIG. 1V, in accordance with an embodiment of the present invention.

FIG. 2A is a schematic diagram of an indwelling portion of a system comprising a ureteral catheter deployed within a patient's urinary tract, in accordance with an embodiment of the present invention.

FIG. 2B is a schematic diagram of an indwelling portion of the system, including a ureteral catheter deployed within a patient's urinary tract, in accordance with an embodiment of the present invention.

FIG. 3 is a biaxial view of an embodiment of a prior art deformable ureteral stent according to FIG. 1 of PCT Patent Application Publication No. WO 2017/019974, the left image representing the uncompressed state of the stent and the right image representing the compressed state of the stent.

FIG. 4 is a perspective view of an embodiment of a prior art ureteral stent according to FIG. 4 of US Patent Application Publication No. 2002/0183853 A1.

FIG. 5 is a perspective view of an embodiment of a prior art ureteral stent according to FIG. 5 of US Patent Application Publication No. 2002/0183853 A1.

FIG. 6 is a perspective view of an embodiment of a prior art ureteral stent according to FIG. 7 of US Patent Application Publication No. 2002/0183853 A1.

FIG. 7A is a schematic diagram of another embodiment of an indwelling portion of a system including a ureteral catheter and a bladder catheter deployed within a patient's urinary tract, in accordance with an embodiment of the present invention.

FIG. 7B is a schematic diagram of a system for inducing negative pressure in a patient's urinary tract, according to an embodiment of the present invention.

FIG. 7C is an enlarged schematic diagram of a portion of a ureteral catheter according to the present invention positioned within the renal pelvis region of a kidney, showing in phantom the general changes believed to occur within the renal pelvic tissue in response to the application of negative pressure through the ureteral catheter.

FIG. 8A is a perspective view of an exemplary catheter, in accordance with an embodiment of the present invention.

FIG. 8B is a front view of the catheter of FIG. 8A.

FIG. 9A is a schematic diagram of an embodiment of a retention portion for a catheter, in accordance with an embodiment of the present invention.

FIG. 9B is a schematic diagram of another embodiment of a retention portion for a catheter, in accordance with an embodiment of the present invention.

FIG. 9C is a schematic diagram of another embodiment of a retention portion for a catheter, in accordance with an embodiment of the present invention.

FIG. 9D is a schematic diagram of another embodiment of a retention portion for a catheter, in accordance with an embodiment of the present invention.

FIG. 9E is a schematic diagram of another embodiment of a retention portion for a catheter, in accordance with an embodiment of the present invention.

FIG. 10 is a front view of another embodiment of a catheter, in accordance with an embodiment of the present invention.

FIG. 10A is a perspective view of the retention portion of the catheter of FIG. 10 encapsulated by a circle 10A, according to an embodiment of the present invention.

10B is a front view of the retention portion of FIG. 10A according to an embodiment of the present invention.

FIG. 10C is a rear view of the retention portion of FIG. 10A according to an embodiment of the present invention.

FIG. 10D is a top view of the retention portion of FIG. 10A in accordance with an embodiment of the present invention.

FIG. 10E is a cross-sectional view of the retention portion of FIG. 10A taken along line 10E-10E, in accordance with an embodiment of the present invention.

Figure 10F is a cross-sectional view of the retention portion of Figure 10A taken along line 10E-10E according to an embodiment of the present invention positioned within the renal pelvis region of the kidney, generally illustrating the changes believed to occur within the renal pelvis tissue in response to the application of negative pressure through a ureteral catheter.

FIG. 10G is a cross-sectional view of the retention portion of FIG. 10A taken along line 10E-10E according to an embodiment of the present invention positioned within the bladder, generally illustrating the changes believed to occur within the bladder tissue in response to the application of negative pressure through a bladder catheter.

FIG. 11 is a schematic diagram of a retaining portion of a catheter in a restrained or linear position, according to an embodiment of the present invention.

FIG. 12 is a schematic diagram of another embodiment of a retention portion of a catheter in a restrained or linear position, in accordance with an embodiment of the present invention.

FIG. 13 is a schematic diagram of another embodiment of a retention portion of a ureteral catheter in a restrained or linear position, in accordance with an embodiment of the present invention.

FIG. 14 is a schematic diagram of another embodiment of a retention portion of a catheter in a restrained or linear position, in accordance with an embodiment of the present invention.

FIG. 15A is a graph showing the percentage of fluid flow through an opening of an exemplary catheter as a function of position, in accordance with an embodiment of the present invention.

FIG. 15B is a graph showing the percentage of fluid flow through an opening of another exemplary catheter as a function of position, in accordance with an embodiment of the present invention.

FIG. 15C is a graph showing the percentage of fluid flow through an opening of another exemplary catheter as a function of position, in accordance with an embodiment of the present invention.

FIG. 16 is a schematic diagram of a retention portion of a catheter showing a station for calculating fluid flow coefficients for mass transfer balance evaluation, in accordance with an embodiment of the present invention.

FIG. 17 is a schematic diagram of an indwelling portion of a system including a ureteral catheter and a bladder catheter deployed within a patient's urinary tract, according to another embodiment of the present invention.

FIG. 18A is a side elevational view of a retention portion of a catheter, in accordance with an embodiment of the present invention.

18B is a cross-sectional view of the retention portion of the catheter of FIG. 18A taken along line BB of FIG. 18A.

18C is a top plan view of the retention portion of the catheter of FIG. 18A taken along line CC of FIG. 18A.

FIG. 18D is a cross-sectional view of a retention portion of a ureteral catheter according to an embodiment of the present invention positioned within the renal pelvis region of a kidney, generally illustrating the changes believed to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter.

FIG. 18E is a cross-sectional view of a retention portion of a bladder catheter according to an embodiment of the present invention positioned within the bladder, generally illustrating the changes that are believed to occur in bladder tissue in response to the application of negative pressure through the bladder catheter.

FIG. 19 is a side elevational view of an alternative catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 20 is a side elevational view of an alternative catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 21 is a side elevational view of an alternative catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 22A is a perspective view of another ureteral catheter retention portion, in accordance with an embodiment of the present invention.

22B is a top plan view of the retention portion of the catheter of FIG. 22A taken along line 22B-22B of FIG. 22A.

FIG. 23A is a perspective view of another catheter retention portion, in accordance with an embodiment of the present invention.

23B is a top plan view of the retention portion of the catheter of FIG. 23A taken along line 23B-23B of FIG. 23A.

FIG. 24A is a perspective view of another catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 24B is a cross-sectional view of a retention portion of a ureteral catheter according to an embodiment of the present invention positioned within the renal pelvis region of a kidney, generally illustrating the changes believed to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter.

FIG. 24C is a cross-sectional view of a retention portion of a bladder catheter according to an embodiment of the present invention positioned within the bladder, generally illustrating the changes that are believed to occur in bladder tissue in response to the application of negative pressure through the bladder catheter.

FIG. 25 is a side elevational view of an alternative catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 26 is a side elevational view of another catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 27 is a cross-sectional side view of an alternative catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 28A is a perspective view of another catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 28B is a top plan view of the retention portion of the catheter of FIG. 28A.

FIG. 29A is a perspective view of another catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 29B is a top plan view of the retention portion of the catheter of FIG. 29A.

FIG. 29C is a cross-sectional view of a retention portion of a ureteral catheter according to an embodiment of the present invention positioned within the renal pelvis region of a kidney, generally illustrating the changes believed to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter.

FIG. 30 is a perspective view of another catheter retention portion, in accordance with an embodiment of the present invention.

31 is a top plan view of the retention portion of the catheter of FIG. 30. FIG.

FIG. 32A is a perspective view of another catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 32B is a top plan view of the retention portion of the catheter of FIG. 32A.

FIG. 33 is a cross-sectional side elevation view of an alternative catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 34 is a cross-sectional side elevation view of an alternative catheter retention portion, in accordance with an embodiment of the present invention.

FIG. 35A is a perspective view of another catheter retention portion, in accordance with an embodiment of the present invention.

35B is a cross-sectional side elevational view of the retention portion of the catheter of FIG. 35A taken along line BB of FIG. 35A.

FIG. 36 is a side elevational view showing a cut-away cross-section of a sheath surrounding a catheter, according to an embodiment of the present invention, in a contracted configuration for insertion into a patient's ureter.

FIG. 37A is a schematic diagram of another embodiment of a retention portion for a catheter, in accordance with an embodiment of the present invention.

FIG. 37B is a schematic illustration of a cross-sectional view of a portion of the retention portion of FIG. 37A taken along line BB of FIG. 37A.

FIG. 38A is a schematic diagram of another embodiment of a retention portion for a catheter, in accordance with an embodiment of the present invention.

FIG. 38B is a schematic illustration of a cross-sectional view of a portion of the retention portion of FIG. 5A taken along line BB of FIG. 38A.

FIG. 39A is a schematic diagram of another embodiment of a retention portion for a catheter, in accordance with an embodiment of the present invention.

Figure 39B is a schematic diagram of a cross-sectional view of another embodiment of a retention portion for a ureteral catheter according to an embodiment of the present invention positioned within the renal pelvis region of a kidney, generally illustrating the changes believed to occur in the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter.

FIG. 39C is a schematic diagram of a cross-sectional view of another embodiment of a retention portion for a bladder catheter according to an embodiment of the present invention positioned within the bladder, generally illustrating changes that are believed to occur in bladder tissue in response to the application of negative pressure through the bladder catheter.

FIG. 40A is a schematic illustration of a cross-sectional view of another embodiment of a retention portion for a catheter, in accordance with an embodiment of the present invention.

Figure 40B is a schematic diagram of a cross-sectional view of another embodiment of a retention portion for a ureteral catheter according to an embodiment of the present invention positioned within the renal pelvis region of a kidney, generally illustrating the changes that are believed to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter.

FIG. 40C is a schematic diagram of a cross-sectional view of another embodiment of a retention portion for a bladder catheter according to an embodiment of the present invention positioned within the bladder, generally illustrating the changes that are believed to occur in bladder tissue in response to the application of negative pressure through the bladder catheter.

FIG. 41A is a schematic diagram of another embodiment of a retention portion for a catheter, in accordance with an embodiment of the present invention.

Figure 41B is a schematic diagram of a cross-sectional view of another embodiment of a retention portion for a ureteral catheter according to an embodiment of the present invention positioned within the renal pelvis region of a kidney, generally illustrating the changes that are believed to occur in the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter.

FIG. 41C is a schematic diagram of a cross-sectional view of another embodiment of a retention portion for a bladder catheter according to an embodiment of the present invention positioned within the bladder, generally illustrating the changes that are believed to occur in bladder tissue in response to the application of negative pressure through the bladder catheter.

FIG. 42A is a flow chart illustrating a process for insertion and deployment of a system according to an embodiment of the present invention.

FIG. 42B is a flow chart illustrating a process for applying negative pressure using a system according to an embodiment of the present invention.

FIG. 43 is a schematic diagram of the renal unit and surrounding vasculature, showing the location of capillary beds and convoluted tubules.

FIG. 44 is a schematic diagram of a system for inducing negative pressure in a patient's urinary tract, in accordance with an embodiment of the present invention.

45A is a top view of a pump for use with the system of FIG. 44, in accordance with an embodiment of the present invention.

FIG. 45B is a side elevational view of the pump of FIG. 45A.

FIG. 46 is a schematic diagram of an experimental setup for evaluating negative pressure therapy in a porcine model, according to an embodiment of the present invention.

FIG. 47 is a graph of creatinine clearance rate for studies performed using the experimental set-up shown in FIG.

FIG. 48A is a low magnification light micrograph of renal tissue from a congested kidney treated with negative pressure therapy.

FIG. 48B is a high magnification light micrograph of the kidney tissue shown in FIG. 48A.

FIG. 48C is a low magnification light micrograph of kidney tissue from a congested and untreated (eg, control) kidney.

FIG. 48D is a high magnification light micrograph of the kidney tissue shown in FIG. 23C.

FIG. 49 is a flow chart illustrating a process for reducing creatinine and/or protein levels in a patient, according to an embodiment of the present invention.

FIG. 50 is a flow chart illustrating a process for treating a patient receiving fluid resuscitation according to an embodiment of the present invention.

FIG. 51 is a graph of serum albumin versus baseline for a study conducted in pigs using the experimental methods described herein.

As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly indicates otherwise.

As used herein, the terms "right", "left", "top" and derivatives thereof shall refer to the present invention as oriented in the drawings. The term "proximal" refers to the portion of the catheter device that is manipulated or contacted by the user and/or the portion of the indwelling catheter closest to the urinary access site. The term "distal" refers to the opposite end of the catheter device that is configured to be inserted into the patient and/or the portion of the device that is inserted most distally of the patient's urinary tract. However, it should be understood that the present invention can assume various alternative orientations and therefore such terms are not to be considered as limiting. It should also be understood that the present invention can assume various alternative modifications and step sequences unless expressly specified to the contrary. It should also be understood that the specific devices and processes illustrated in the accompanying drawings and described in the following specification are examples. Therefore, specific dimensions and other physical characteristics associated with the embodiments disclosed herein are not to be considered as limiting.

For purposes of this specification, unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, dimensions, physical properties, and the like used in the specification and claims are to be understood as being modified in all instances by the term "about." Unless indicated to the contrary, the numerical parameters set forth in the following specification and appended claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention.

Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

It should also be understood that any numerical range recited herein is intended to include all subranges subsumed therein. For example, a range of "1 to 10" is intended to include the minimum recited value of 1 and the maximum recited value of 10, including all ranges therebetween, i.e., all subranges starting with a minimum value equal to or greater than 1 and ending with a maximum value equal to or less than 10, and all subranges therebetween, e.g., 1 to 6.3, or 5.5 to 10, or 2.7 to 6.1.

As used herein, the terms "communication" and "communicating" refer to the receipt or transfer of one or more signals, messages, commands, or other types of data. For one unit or component to communicate with another unit or component means that the one unit or component is able to receive data from and/or transmit data to the other unit or component, directly or indirectly. This may refer to a direct or indirect connection, which may be wired and/or wireless in nature. In addition, two units or components may communicate with each other even if the data transmitted is modified, processed, routed, and the like between the first and second units or components. For example, a first unit may communicate with a second unit even if the first unit passively receives data and does not actively transmit data to the second unit. As another example, a first unit may communicate with a second unit even if an intermediate unit processes data from the one unit and transmits the processed data to the second unit. It should be understood that numerous other arrangements are also possible.

As used herein, "maintaining patency of fluid flow between a patient's kidney and bladder" means establishing, increasing, or maintaining the flow of fluid, such as urine, from the kidney through the ureter, ureteral stent, and/or ureteral catheter to the bladder and outside the body. In some examples, fluid flow is promoted or maintained by providing a protective surface area 1001 within the upper urinary tract and/or bladder to prevent the urinary tract endothelium from contracting or collapsing into the fluid column or flow. As used herein, "fluid" means urine and any other fluid from the urinary tract.

As used herein, "negative pressure" means that the pressure applied to the proximal end of the bladder catheter or the proximal end of the ureteral catheter, respectively, is less than the pre-existing pressure at the proximal end of the bladder catheter or the proximal end of the ureteral catheter, respectively, prior to application of the negative pressure, e.g., there is a pressure difference between the proximal end of the bladder catheter or the proximal end of the ureteral catheter, respectively, and the pre-existing pressure at the proximal end of the bladder catheter or the proximal end of the ureteral catheter, respectively, prior to application of the negative pressure. This pressure difference causes fluid from the kidney to be drawn into the ureteral catheter or the bladder catheter, respectively, or through both the ureteral catheter and the bladder catheter, and then outside the patient's body. For example, the negative pressure applied to the proximal end of the bladder catheter or the proximal end of the ureteral catheter may be less than atmospheric pressure (less than about 760 mmHg or about 1 atmosphere) or less than the pressure measured at the proximal end of the bladder catheter or the proximal end of the ureteral catheter prior to application of the negative pressure, such that fluid is drawn from the kidney and/or bladder. In some embodiments, the negative pressure applied to the proximal end of the bladder catheter or the proximal end of the ureteral catheter can range from about 0.1 mmHg to about 150 mmHg, or about 0.1 mmHg to about 50 mmHg, or about 0.1 mmHg to about 10 mmHg, or about 5 mmHg to about 20 mmHg, or about 45 mmHg (gauge pressure at the pump 710 or gauge pressure at the negative pressure source). In some embodiments, the negative pressure source comprises a pump outside the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body. In some embodiments, the negative pressure source comprises a vacuum source external to the patient's body for application and regulation of negative pressure through both the bladder catheter and the ureteral catheter, which in turn draws fluid from the kidney into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body. In some embodiments, the vacuum source is selected from the group consisting of a wall suction source, a vacuum bottle, and a manual vacuum source, or the vacuum source is provided by a pressure differential. In some embodiments, the negative pressure received from the negative pressure source can be controlled manually, automatically, or a combination thereof. In some embodiments, a controller is used to regulate the negative pressure from the negative pressure source. Non-limiting examples of negative and positive pressure sources are discussed in detail below.

As used herein, "positive pressure" means that the pressure applied to the proximal end of the bladder catheter or the proximal end of the ureteral catheter, respectively, exceeds the existing pressure at the proximal end of the bladder catheter or the proximal end of the ureteral catheter, respectively, prior to the application of the negative pressure, causing fluid present in the ureteral catheter or bladder catheter, or through both the ureteral catheter and the bladder catheter, respectively, to flow back toward the bladder or kidney. In some examples, the positive pressure applied to the proximal end of the bladder catheter or the proximal end of the ureteral catheter can range from about 0.1 mmHg to about 150 mmHg, or about 0.1 mmHg to about 50 mmHg, or about 0.1 mmHg to about 10 mmHg, or about 5 mmHg to about 20 mmHg, or about 45 mmHg (gauge pressure at the pump 710 or gauge pressure at the positive pressure source). The positive pressure source can be provided, for example, by a pump or a wall pressure source, or a pressurized bottle, and can be controlled manually, automatically, or a combination thereof. In some embodiments, a controller is used to regulate the positive pressure from the positive pressure source.

Fluid retention and venous stasis are major problems in the progression of progressive renal disease. Excessive sodium intake coupled with a relative decrease in excretion leads to isotonic volume expansion and secondary compartment syndrome complications. In some embodiments, the present invention is generally directed to devices and methods for facilitating the evacuation of urine or waste products from a patient's bladder, ureters, and/or kidneys. In some embodiments, the present invention is generally directed to systems and methods for inducing negative pressure within a patient's bladder, ureters, and/or kidneys, e.g., at least a portion of the urinary system. Without intending to be bound by any theory, it is believed that applying negative pressure to the bladder, ureters, and/or kidneys, e.g., at least a portion of the urinary system, may compensate for medullary renal unitary tubule reabsorption of sodium and water in some circumstances. Compensating sodium and water reabsorption can increase urine production, reduce total body sodium, and improve red blood cell production. Because intramedullary pressure is driven by sodium, and therefore by volume excess, targeted removal of excess sodium allows for the maintenance of volume loss. Removal of fluid volume reverses medullary congestion. Normal urine production is 1.48-1.96 L/day (or 1-1.4 ml/min).

Fluid retention and venous stasis are also major problems in the progression of prerenal acute kidney injury (AKI). Specifically, AKI can be associated with loss of perfusion or blood flow through the kidney. Thus, in some embodiments, the present invention promotes improved renal hemodynamics and increases urination for the purpose of alleviating or reducing venous stasis. Furthermore, treating and/or preventing AKI is expected to positively affect and/or reduce the occurrence of other conditions, such as reducing or preventing the deterioration of renal function in patients with NYHA Class III and/or Class IV heart failure. Classification of different levels of heart failure is explained in The Criteria Committee of the New York Heart Association, (1994), Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels, (9th ed.), Boston: Little, Brown and Co. pp. 253-256, the disclosure of which is incorporated herein by reference in its entirety. Reducing or preventing episodes of AKI and/or chronic hypoperfusion may also be a treatment for Stage 4 and/or Stage 5 chronic kidney disease. The progression of chronic kidney disease is described in the National Kidney Foundation, K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Strategy. Am. J. Kidney Dis. 39:S1-S266, 2002 (Suppl. 1), the disclosure of which is incorporated herein by reference in its entirety.

The ureteral catheters, ureteral stents, and/or bladder catheters disclosed herein may also be useful for preventing, delaying the onset of, and/or treating end-stage renal disease ("ESRD"). The average dialysis patient consumes approximately $90,000 per year in healthcare utilization for a total cost to the U.S. government of $33.9 billion. Currently, ESRD patients comprise only 2.9% of all Medicare beneficiaries but account for over 13% of total expenditures. While incidence and cost per patient have stabilized in recent years, active patient volume continues to rise.

Five stages of progressive chronic kidney disease ("CKD") are based on glomerular filtration rate (GFR). Stage 1 (GFR>90) patients have normal filtration, while stage 5 (GFR<15) have renal failure. As with many chronic diseases, diagnostic coverage improves with increasing symptoms and disease severity.

The CKD3b/4 subgroup is a smaller subgroup that reflects important changes in disease progression, health care system involvement, and transition to ESRD. Emergency department visits increase with CKD severity. Among the US Veterans Affairs population, nearly 86% of incident dialysis patients were hospitalized within the 5 years preceding hospitalization. Of those, 63% were hospitalized at the initiation of dialysis. This suggests a tremendous opportunity to intervene prior to dialysis.

Despite being further down the arterial tree than other organs, the kidneys receive a disproportionate amount of cardiac output at rest. The glomerular membrane represents the path of least resistance for the filtrate into the renal tubule. In the healthy state, the renal unit has multiple complex and redundant means of autoregulation within the normal range of arterial pressure.

Venous congestion is responsible for reduced renal function and is associated with the systemic hypervolemia seen in late-stage CKD. Because the kidneys are covered by a semi-rigid capsule, small changes in venous pressure are translated into direct changes in intratubular pressure. This shift in intratubular pressure has been shown to upregulate sodium and water reabsorption, perpetuating a vicious cycle.

Regardless of initial insult and early progression, more progressive CKD is associated with decreased filtration (by definition) and further azotemia. Whether the remaining renal units are overabsorbing fluid or simply unable to filter adequately, this renal unit loss is associated with fluid retention and progressive decline in renal function.

The kidneys are sensitive to subtle shifts in volume. As pressure rises in either the tubule or capillary bed, pressure in the other follows. As capillary bed pressure rises, filtrate production and urine elimination can decrease dramatically. Without intending to be bound by any theory, it is believed that a slight and regulated negative pressure delivered to the renal pelvis reduces pressure between each of the functioning renal units. In healthy anatomy, the renal pelvis is connected to approximately one million individual renal units via the calyces and collecting duct network. Each of these renal units is essentially a column of fluid connecting the Bowman's space to the renal pelvis. Pressure transmitted to the renal pelvis translates throughout. It is believed that as negative pressure is applied to the renal pelvis, glomerular capillary pressure forces more filtrate across the glomerular membrane, leading to increased urination.

It is important to note that the tissues of the urinary tract are lined with urothelium, a type of transitional epithelium. The inner tissue lining of the urinary tract is also referred to as urinary tract endothelium or urothelial tissue, such as the mucosal tissue 1003 of the ureter and/or kidney and bladder tissue 1004. The urothelium has a very high elasticity, allowing a remarkable range of collapsibility and extensibility. The urothelium lining the ureter lumen is first surrounded by the lamina propria, a thin layer of loose connective tissue, which together comprise the urothelial mucosa. This mucosa is then surrounded by a layer of longitudinal muscle fibers. These longitudinal muscle fibers surrounding the urothelial mucosa and the elasticity of the urothelial mucosa itself allow the ureter to relax into a collapsed stellate cross-section and then expand to full distention during diuresis. The histology of any normal ureter cross-section generally reveals this star-shaped lumen in humans and other mammals used in translational medical research. Wolf et al. , "Comparative Urethral Microanatomy", JEU 10: 527-31 (1996).

The process of transporting urine from the kidney to the bladder is driven by contractions through the renal pelvis and peristalsis distally through the remainder of the ureter. The renal pelvis is the enlargement of the proximal ureter into a funnel shape where the ureter enters the kidney. It has been shown that the renal pelvis is in fact a continuation of the ureter, composed of the same tissue but with one additional layer of muscle that allows it to contract. Dixon and Gosling, "The Musculature of the Human Renal Calyces, Pelvis and Upper Ureter", J. Anat. 135: 129-37 (1982). These contractions push urine through the renal pelvis funnel, allowing peristaltic waves to propagate fluid through the ureter to the bladder.

Imaging studies have shown that the dog ureter can easily increase up to 17 times its resting cross-sectional area and accommodate large volumes of urine during diuresis. Woodburne and Lapides, "The Ureteral Lumen During Peristalsis", AJA 133: 255-8 (1972). In the pig, which is considered the closest animal model for the human upper urinary tract, the renal pelvis and most proximal ureter have been shown to be, in fact, the most flexible of all ureteral segments. Gregersen, et al., "Regional Differences Exist in Elastic Wall Properties in the Ureter", SJUN 30: 343-8 (1996). Wolf's comparative studies of human ureteral microanatomy with that of various study animals revealed comparable thickness of lamina propria to total ureteral diameter in dogs (29.5% in humans and 34% in dogs), and comparable proportions of smooth muscle to total muscle cross-sectional area in pigs (54% in humans and 45% in pigs). Although limitations to comparisons between species certainly exist, dogs and pigs have been strong focuses in studying and understanding human ureteral anatomy and physiology, and these reference values support this high level of translational potential.

There is much more data available on the structure and mechanics of the porcine and canine ureter and renal pelvis than the human ureter. This is due, in part, to the invasiveness required for such detailed analysis, as well as the inherent limitations of various imaging modalities (MRI, CT, ultrasound, etc.) to attempt to clinically accurately identify the size and composition of such small, flexible, dynamic structures. Nonetheless, the ability of the renal pelvis to expand or completely collapse in humans is an obstacle for nephrologists and urologists seeking to improve urinary flow.

While not intending to be bound by any theory, the inventors theorize that application of negative pressure may help facilitate fluid flow from the kidney, and that a very specific tool designed to deploy a protective surface area to open or maintain the interior of the renal pelvis open while preventing the surrounding tissue from contracting or collapsing into a fluid column under negative pressure is required to facilitate application of negative pressure within the renal pelvis. The inventive catheter design disclosed herein provides a protective surface area to prevent the surrounding urothelial tissue from contracting or collapsing into a fluid column under negative pressure. It is believed that the inventive catheter design disclosed herein may normally maintain the stellate longitudinal folding of the ureteral wall away from the central axis of the catheter drainage lumen and the protected holes, preventing natural sliding and/or downward movement of the catheter following the stellate cross-sectional area of the ureteral lumen by peristaltic waves.

The inventive catheter design disclosed herein also avoids an unprotected open hole at the distal end of the drainage lumen that cannot protect the surrounding tissue during aspiration. Although it is convenient to consider the ureter as a straight tube, the true ureter and renal pelvis may enter the kidney at various angles. Lippincott Williams & Wilkins, Annals of Surgery, 58, Figs 3 & 9 (1913). Thus, it would be difficult to control the orientation of the unprotected open hole at the distal end of the drainage lumen when deploying such a catheter within the renal pelvis. The single hole does not have any means of ensuring a reliable or consistent distance from the tissue wall, thereby allowing tissue to occlude the unprotected open hole and presenting a localized aspiration point with risk of injury to the tissue. Additionally, the inventive catheter designs disclosed herein can avoid placement of a balloon with an unprotected open hole at the distal end of the draining lumen near the kidney, which can result in suction against and/or obstruction of the calyx. Placement of a balloon with an unprotected open hole at the distal end of the draining lumen at the base of the ureteropelvic junction can result in suction against and obstruction by the renal pelvic tissue. Also, rounded balloons can present a risk of ureteral avulsion or other injury from incidental traction on the balloon.

Delivering negative pressure into the renal area of a patient poses several anatomical challenges for at least three reasons. First, the urinary system is composed of highly flexible tissue that is easily deformed. Medical texts often depict the bladder as a thick muscular structure that can remain in a fixed shape regardless of the volume of urine contained within the bladder. In reality, however, the bladder is a soft, deformable structure. It contracts and conforms to the volume of urine contained within the bladder. An empty bladder resembles a deflated latex balloon more than a ball. In addition, the mucosal lining inside the bladder is soft and prone to inflammation and injury. It is desirable to avoid drawing urinary system tissue into the orifice of the catheter, maintaining proper fluid flow therethrough and avoiding injury to the surrounding tissue.

Second, the ureter is a small tubular structure that can expand and contract to transport urine from the renal pelvis to the bladder. This transport occurs in two ways: peristaltic action and pressure gradients in an open system. In peristaltic action, urine portions are pushed ahead of a contractile wave that almost completely occludes the lumen. The wave pattern starts in the renal pelvic area, propagates along the ureter, and terminates at the bladder. Such a complete obstruction would interrupt the fluid flow and prevent the negative pressure delivered in the bladder from reaching the renal pelvis unassisted. A second type of transport, due to a pressure gradient through a wide open ureter, may exist during large volumes of urine flow. During such periods of large volume urine production, the pressure head in the renal pelvis would not necessarily be caused by contraction of the smooth muscle of the upper urinary tract, but rather would be generated by the forward flow of urine and would thus reflect arterial blood pressure. Kiil F. "Urinary Flow and Urethral Peristalsis" in: Lutzeyer W. , Melchior H. (eds) Urodynamics. Springer, Berlin, Heidelberg (pp.57-70) (1973).

Third, the renal pelvis is at least as flexible as the bladder. The thin walls of the renal pelvis can expand and accommodate multiple times its normal volume, as occurs, for example, in patients with hydronephrosis.

More recently, the use of negative pressure within the renal pelvis to remove thrombi from the renal pelvis by use of suction has been cautioned against due to the inevitable collapse of the renal pelvis, thus precluding the use of negative pressure within the renal pelvic region. Webb, Percutaneous Renal Surgery: A Practical Clinical Handbook. p 92. Springer (2016).

While not intending to be bound by any theory, the renal pelvis and bladder tissues are flexible enough to be drawn inward during delivery of negative pressure, conforming to the shape and volume of the tool being used to deliver the negative pressure. Similar to the vacuum seal of an ear of corn with a husk, the urothelial tissue will collapse around and conform to the negative pressure source. To prevent the tissue from occluding the lumen and impeding urine flow, the inventors theorize that sufficient protective surface area to maintain a fluid column when minor negative pressure is applied will prevent or discourage occlusion.

The inventors have determined that there are specific features that allow catheter tools to be successfully deployed in and deliver negative pressure through urological regions not previously described. These require a deep understanding of the anatomy and physiology of the treatment zone and adjacent tissues. The catheter must provide a protective surface area within the renal pelvis by supporting the urothelium and preventing the urothelial tissue from occluding the openings within the catheter during application of negative pressure through the catheter lumen. For example, establishing a three-dimensional shape or void volume that is free or essentially free of urothelial tissue ensures patency of the fluid column or flow from each of the one million renal units into the drainage lumen of the catheter.

Because the renal pelvis is composed of longitudinally oriented smooth muscle cells, the protective surface area would ideally incorporate a multiplanar approach to establishing the protected surface area. The anatomy is often described in three planes: sagittal (vertical anterior-posterior dividing the body into right and left portions), coronal (vertical left-right dividing the body into dorsal and ventral portions), and transverse (horizontal or axial dividing the body into superior and inferior portions and perpendicular to the sagittal and coronal planes). The smooth muscle cells within the renal pelvis are vertically oriented. It is desirable for the catheter to also maintain radial surface area across the many transverse planes between the kidney and the ureter. This allows the catheter to account for both the longitudinal and horizontal portions of the renal pelvis in establishing the protective surface area 1001. In addition, given the flexibility of the tissue, protection of these tissues from openings or orifices leading to the lumen of the catheter tool is desirable. The catheters discussed herein may be useful for delivering negative pressure, positive pressure, or may be used at ambient pressure, or any combination thereof.

In some embodiments, a deployable/retractable expansion mechanism is utilized that, when deployed, creates and/or maintains a patent fluid column or flow between the kidney and the catheter drainage lumen. When deployed, the deployable/retractable mechanism creates a protective surface area 1001 within the renal pelvis by supporting the urothelium and preventing the urothelial tissue from blocking the opening in the catheter during application of negative pressure through the catheter lumen. In some embodiments, the retention portion is configured to extend to a deployed position in which the diameter of the retention portion exceeds the diameter of the drainage lumen portion.

1A-1C, 1F, 1P, 1U, 2A, 2B, 7A, 7B, 17, and 44, the urinary tract generally shown at 1 comprises a right kidney 2 and a left kidney 4 of a patient. As discussed above, the kidneys 2, 4 are involved in blood filtration and clearance of waste compounds from the body through urine. Urine produced by the right kidney 2 and the left kidney 4 is drained through renal tubules, i.e., the right ureter 6 and the left ureter 8, into the patient's bladder 10. For example, urine may be conducted through the ureters 6, 8 by peristalsis of the ureteral walls as well as by gravity. The ureters 6, 8 enter the bladder 10 through ureteral orifices or openings 16. The bladder 10 is a flexible and substantially hollow structure adapted to collect urine until it is excreted from the body. The bladder 10 is transitionable from an empty position (indicated by reference line E) to a full position (indicated by reference line F). When the bladder is in the empty position E, the upper bladder wall 70 may be positioned adjacent to and/or conform to the outer periphery 72, 1002 or protective surface area 1001 of the distal end 136 of the bladder catheter 56, 116, shown, for example, as mesh 57 in Figures 1A and 1B, as coil 1210 in Figures 1C, 1U, and 7A, as basket-shaped structure or support cap 212 of the upper bladder wall support 210 in Figure 1F, as annular balloon 310 in Figure 1P, and as funnel 116 in Figure 17. Typically, when the bladder 10 reaches a substantially full state, urine is allowed to drain from the bladder 10 into the urethra 12 through the urethral sphincter or orifice 18 located in the lower portion of the bladder 10. Contraction of the bladder 10 may be in response to stress and pressure exerted on the trigone region 14 of the bladder 10, which is a triangular region extending between the ureteral orifice 16 and the urethral orifice 18. The trigone region 14 is sensitive to stress and pressure such that as the bladder 10 begins to fill, the pressure on the trigone region 14 increases. Once a threshold pressure on the trigone region 14 is exceeded, the bladder 10 begins to contract, expelling collected urine through the urethra 12.

Similarly, as shown in Figures 1A, 1B, 1C, 1F, 1P, 1U, 2A, and 2B, for example, the outer periphery 72, 1002 or protective surface area 1001 of the ureteral catheter 112, 114 of the present invention can support ureteral and/or renal tissue 1003 and maintain patency of fluid flow between the patient's kidney and bladder.

In some embodiments, a method and system 50, 100, as shown, for example, in Figures 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7, 17, and 44, is provided for removing fluid (such as urine) from a patient, the method including the steps of deploying a ureteral stent 52, 54 (shown in Figure 1A) or a ureteral catheter 112, 114 (shown in Figures 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7, 17, and 44) in the patient's ureter 6, 8 to maintain patency of fluid flow between the patient's kidneys 2, 4 and bladder 10. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7, 17, and/or a bladder catheter 56, 116, comprising a distal end 136 configured to be positioned within the patient's bladder 10, a drainage lumen portion 140 having a proximal end 117, and a sidewall 119 extending therebetween, and applying a negative pressure to the proximal end 117 of the bladder catheter 56, 116 and/or the ureteral catheter 112, 114 to induce a negative pressure within a portion of the patient's urinary tract and remove fluid from the patient. In some examples, the method further includes deploying a second ureteral stent or a second ureteral catheter into a second ureter or kidney of the patient to maintain patency of fluid flow between the patient's second kidney and the bladder, as shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7, 17, and 44. Specific characteristics of exemplary ureteral stents or ureteral catheters of the present invention are described in detail below.

In some non-limiting examples, a ureteral or bladder catheter 56, 112, 114, 116, 312, 412, 512, 812, 1212, 5000, 5001 comprises (a) a proximal portion 117, 128, 1228, 5006, 5007, 5017, and (b) a distal portion 118, 318, 1218, 5004, 5005, the distal portion comprising one or more protected drainage holes, ports, or perforations 133, 533, 1233, to allow the catheter to be The retention portion 130, 330, 410, 500, 1230, 1330, 2230, 3230, 4230, 5012, 5013 is configured to establish an outer periphery 1002 or protective surface area 1001 that prevents urothelial tissue, such as mucosal tissue 1003 of the ureter and/or kidney and bladder tissue 1004, from obstructing one or more protected drainage holes, ports, or perforations 133, 533, 1233 in response to application of negative pressure therethrough.
Exemplary ureteral catheters:

2A, 7, 17, and 44, an embodiment of the system 100 is illustrated that includes a ureteral catheter 112, 114 configured to be positioned within the urinary tract of a patient. For example, the distal end 120, 121, 1220, 5019, 5021 of the ureteral catheter 112, 114 can be configured to be deployed within at least one of the ureters 2, 4, the renal pelvis 20, 21 area of the kidney 6, 8, or the kidney 6, 8 of the patient.

In some embodiments, suitable ureteral catheters are disclosed in U.S. Pat. No. 9,744,331, U.S. Patent Application Publication No. US2017/0021128A1, U.S. Patent Application No. 15/687,064, and U.S. Patent Application No. 15/687,083, each of which is incorporated herein by reference.

In some embodiments, the system 100 can include two separate ureteral catheters, such as a first catheter 112 positioned in or adjacent to the renal pelvis 20 of the right kidney 2, and a second catheter 114 positioned in or adjacent to the renal pelvis 21 of the left kidney 4. The catheters 112, 114 can be separate for their entire length or can be held in close proximity to each other by a clip, ring, clamp, or other type of connection mechanism (e.g., connector) to facilitate placement or removal of the catheters 112, 114. As shown in Figures 2A, 7, 17, 27, and 44, the proximal end 113, 115 of each catheter 112, 114 is positioned at the proximal end of the ureter in or near the bladder 10 to drain fluid or urine into the bladder. In some embodiments, the proximal end 113, 115 of each catheter 112, 114 can be in fluid communication with the distal portion or end 136 of the bladder catheter 56, 116. In some embodiments, the catheters 112, 114 can be fused or connected together within the bladder to form a single drainage lumen that drains into the bladder 10.

As shown in FIG. 2A, in some embodiments, the proximal ends 113, 115 of one or both of the catheters 112, 114 can be positioned within the urethra 12 and can optionally be connected to additional drainage tubing for draining fluids outside the patient's body. As shown in FIG. 2B, in some embodiments, the proximal ends 113, 115 of one or both of the catheters 112, 114 can be positioned to extend from the urethra 12 to the outside of the patient's body.

In other embodiments, the catheters 112, 114 may be inserted through or enclosed along a portion or section of another catheter, tube, or sheath to facilitate insertion and retraction of the catheters 112, 114 into and from the patient's body. For example, the bladder catheter 116 may be inserted over and/or along the same guidewire as the ureteral catheters 112, 114, or within the same tubing used to insert the ureteral catheters 112, 114.

1B, 1C, 1F, 1P, 1U, 2A, 2B, 7, 8A, and 8B, an exemplary ureteral catheter 112, 1212, 5000 can include at least one elongated body or tube 122, 1222, 5009, the interior of which defines or includes one or more drainage channels or lumens, such as drainage lumen 124, 1224, 5002. The tube 122, 1222, 5009 size can range from about 1 Fr to about 9 Fr (French catheter scale). In some examples, the tube 122, 1222, 5009 can have an outer diameter ranging from about 0.33 to about 3 mm and an inner diameter ranging from about 0.165 to about 2.39 mm. In one example, the tube 122 is 6 Fr and has an outer diameter of 2.0±0.1 mm. The length of the tubes 122, 1222, 5009 can range from about 30 cm to about 120 cm, depending on the age (e.g., pediatric or adult) and gender of the patient.

The tube 122, 1222, 5009 may be formed from a flexible and/or deformable material to facilitate advancement and/or positioning of the tube 122, 1222, 5009 within the bladder 10 and ureters 6, 8 (shown in FIGS. 2 and 7). The catheter material should be sufficiently flexible and soft to avoid or reduce irritation of the renal pelvis and ureters, yet sufficiently rigid so that the tube 122, 1222, 5009 does not collapse when the renal pelvis or other parts of the urinary tract apply pressure to the exterior of the tube 122, 1222, 5009 or when the renal pelvis and/or ureters are pulled against the tube 122, 1222, 5009 during induction of negative pressure. For example, the tube 122, 1222, 5009 or drainage lumen can be formed at least in part from one or more materials including copper, silver, gold, nickel-titanium alloy, stainless steel, titanium, and/or polymers such as biocompatible polymers, polyurethane, polyvinyl chloride, polytetrafluoroethylene (PTFE), latex, silicone coated latex, silicone, silicone, polyglycolide or poly(glycolic acid) (PGA), polylactic acid (PLA), poly(lactic-co-glycolic acid), polyhydroxyalkanoic acid, polycaprolactone, and/or poly(propylene fumarate). In one example, the tube 122, 1222, 5009 is formed from a thermoplastic polyurethane. The tube 122, 1222, 5009 can also include or be impregnated with one or more of copper, silver, gold, nickel-titanium alloy, stainless steel, and titanium. In some embodiments, the tube 122, 1222, 5009 is impregnated with or formed from a material that is visible by fluoroscopic imaging. For example, the biocompatible polymer forming the tube 122, 1222, 5009 can be impregnated with barium sulfate or a similar radiopaque material. Thus, the structure and position of the tube 122, 1222, 5009 is visible to fluoroscopy.

At least a portion or all of the interior or exterior of the catheter 112, 1212, 5000, e.g., tube 122, 1222, 5009, can be coated with a hydrophilic coating to facilitate insertion and/or removal and/or to improve comfort. In some embodiments, the coating is a hydrophobic and/or lubricious coating. For example, a suitable coating can comprise ComfortCoat® hydrophilic coating available from Koninklijke DSM N.V., or a hydrophilic coating comprised of polyelectrolytes as disclosed in U.S. Pat. No. 8,512,795, incorporated herein by reference.

In some embodiments, for example, as shown in FIG. 8B , the tube 122 can comprise a distal portion 118 (e.g., a portion of the tube 122 configured to be positioned within the ureters 6, 8 and renal pelvis 20, 21), a middle portion 126 (e.g., a portion of the tube 122 configured to extend from the distal portion 118 through the ureteral orifice 16 into the patient's bladder 10 and urethra 12), and a proximal portion 128 (e.g., a portion of the tube 122 that extends into the bladder 10 or urethra 12, or from the urethra 12 to the outside of the patient's body). In one embodiment, the combined length of the proximal portion 128 and middle portion 126 of the tube 122 is about 54±2 cm. In some embodiments, the tube 122 terminates within the bladder 10. Fluid then drains from the proximal end of the ureteral catheters 112, 114 and is directed out of the body through an additional indwelling bladder catheter. In other embodiments, the tube 122 terminates within the urethra 12, e.g., a bladder catheter is not required. In other embodiments, the tube extends from the urethra 12 to outside the patient's body, e.g., a bladder catheter is not required.
Exemplary ureteral retention segments:

Any of the retention portions disclosed herein can be formed from the same materials as the drainage lumen discussed above and can be integral with or connected to the drainage lumen, or the retention portion can be formed from a different material and connected thereto, such as those discussed above with respect to the drainage lumen. For example, the retention portion can be formed from any of the aforementioned materials, such as polyurethane, flexible polyvinyl chloride, polytetrafluoroethylene (PTFE), latex, silicone, silicon, polyglycolide or polymers such as poly(glycolic acid) (PGA), polylactic acid (PLA), poly(lactic-co-glycolic acid), polyhydroxyalkanoic acid, polycaprolactone, and/or poly(propylene fumarate).

Generally, as shown, for example, in FIGS. 2A-C, 8A, and 8B, the distal portion 118 of the ureteral catheter 112 includes a retaining portion 130 for maintaining the distal end 120 of the catheter 112 in a desired fluid collection position adjacent to or within the renal pelvis 20, 21 of the kidney 2, 4. In some embodiments, the retaining portion 130 is configured to be flexible and bendable to allow the retaining portion 130 to be positioned within the ureter and/or renal pelvis. The retaining portion 130 is desirably bendable enough to absorb forces exerted on the catheter 112 and to prevent such forces from being transmitted to the ureter. For example, when the retaining portion 130 is pulled in a proximal direction P (shown in FIG. 9A) toward the patient's bladder, the retaining portion 130 may be sufficiently flexible to begin to uncoil or straighten so that it may be pulled through the ureter. Similarly, when the retention portion 130 can be reinserted into the renal pelvis or other suitable region within the ureter, it can be biased back to its deployed configuration.

In some embodiments, the retention portion 130 is integral with the tube 122. In that case, the retention portion 130 can be formed by imparting a bend or inflection to the catheter body 122 that is sized and shaped to retain the catheter at the desired fluid collection location. Suitable bends or coils can include pigtail coils, cork screw coils, and/or helical coils, as shown in Figures 1, 2A, 7A, and 8A-10G. For example, the retention portion 130 can comprise one or more radially and longitudinally extending helical coils configured to passively retain the catheter 112 in the ureter 6, 8 adjacent to or in contact with the renal pelvis 20, 21, as shown, for example, in Figures 2A, 7A, and 8A-10G. In other embodiments, the retention portion 130 is formed from a radially flared or tapered portion of the catheter body 122. For example, the retention portion 130 can further comprise a fluid collection portion as shown in FIG. 17-41C, such as a tapered or funnel-shaped inner surface 186. In other embodiments, the retention portion 130 can comprise a separate element that is connected to and extends from the catheter body or tube 122.

In some embodiments, the retention portion 130 can further include one or more perforation sections, such as drainage holes, perforations, or ports 132, 1232 (e.g., as shown in Figs. 9A-9E, 10A, 10E, 11-14, 27, 32A, 32B, 33, 34, and 39-41A-C). The drainage port 132 can be located at the open distal end 120, 121 of the tube 122, as shown in Fig. 10D, for example. In other embodiments, the perforation sections and/or drainage ports 132, 1232 are located along the sidewall 109 of the distal portion 118 of the catheter tube 122, as shown in Figs. 9A-9E, 10A, 10E, 11-14, 27, 32A, 32B, 33, 34, and 41A-C, or within the material of the retention portion, such as the sponge material of Figs. 39 and 40. The drainage port or hole 132, 1232 can be used to assist in fluid collection, allowing fluid to flow into the drainage lumen for removal from the patient's body. In other embodiments, the retention portion 130 is a dedicated reservoir structure and fluid collection and/or application of negative pressure is provided by structures elsewhere on the catheter tube 122.

In some embodiments, such as those shown in Figures 9B-E, 10D-G, 18B, 18C-E, 20, 22A-35, 37B, 38A, 39B, 40A-41C, at least a portion, most, or all of the drainage hole, port, or perforation 132, 1232 is positioned within the ureteral catheter 112, 114 or bladder catheter 116 within a protected surface or inner surface area 1000 such that tissue 1004, 1003 from the bladder or kidney does not directly contact or partially or completely obstruct the protected drainage hole, port, or perforation 133. For example, as shown in Figures 2A-2C, 7A, 7B, 10F, 17, 18D, 24B, 29C, 39B, 40B, and 41B, when negative pressure is induced within the ureter and/or renal pelvis, a portion of the ureteral and/or renal mucosal tissue 1003 may be pulled against the outer periphery 72, 1002 or protective surface area 1001 or outer region of the retention portion 130, and may partially or completely occlude certain drainage holes, ports, or perforations 134 located on the outer periphery 72, 1002 or protective surface area 1001 of the retention portion 130. Similarly, as shown in Figures 2A-2C, 7A, 7B, 10G, 17, 18E, 24C, 39C, 40C, and 41C, when negative pressure is induced in the bladder, portions of the bladder tissue 1004, such as the transitional epithelial tissue lining, the lamina propria connective tissue, the muscularis propria, and/or the fatty connective tissue, may be pulled against the outer periphery 72, 1002 or protective surface area 1001 or outer region of the retention portion 130, partially or completely occluding some of the drainage holes, ports, or perforations 134 located on the outer periphery 1002 or protective surface area 1001 or outer region of the retention portion 130.

At least a portion of the protected evacuation port 133 located on the protected surface area or inner surface area 1000 of the retention portion 130 will not be partially or completely occluded when such tissue 1003, 1004 contacts the outer periphery 72, 1002 or the protected surface area 1001 or outer region of the retention portion 130. Furthermore, the risk of injury to the tissue 1003, 1004 from biting or contact with the evacuation port 133 can be reduced or ameliorated. The configuration of the outer periphery 72, 1002 or the protected surface area 1001 or outer region of the retention portion 130 depends on the overall configuration of the retention portion 130. Generally, the outer periphery 72, 1002 or the protected surface area 1001 or outer region of the retention portion 130 contacts and supports the bladder 1004 or kidney tissue 1003, thereby preventing blockage or obstruction of the protected evacuation hole, port, or perforation 133.

10E-G, an exemplary retention portion 1230 is shown comprising a plurality of helical coils 1280, 1282, 1284. The outer periphery 1002 or protective surface area 1001 or outer region of the helical coils 1280, 1282, 1284 contacts and supports the bladder tissue 1004 or kidney tissue 1003 and prevents occlusion or obstruction of the protected drainage hole, port, or perforation 1233 located within the protected or inner surface area 1000 of the helical coils 1280, 1282, 1284. The outer periphery 1002 or protective surface area 1001 or outer region of the helical coils 1280, 1282, 1284 provides protection for the protected drainage hole, port, or perforation 1233. In FIG. 10F , renal tissue 1003 is shown surrounding and contacting at least a portion of the outer periphery 1002 or protected surface area 1001 or outer region of the helical coils 1280, 1282, 1284, which prevents contact of the renal tissue 1003 with the protected or inner surface area 1000 of the helical coils 1280, 1282, 1284, thereby preventing partial or complete obstruction of the protected drainage hole, port, or perforation 1233 by the renal tissue 1003. In FIG. 10G, the bladder tissue 1004 is shown surrounding and contacting at least a portion of the outer periphery 1002 or protected surface area 1001 or outer region of the helical coils 1280, 1282, 1284, which prevents contact of the bladder tissue 1004 with the protected or inner surface area 1000 of the helical coils 1280, 1282, 1284, thereby preventing partial or complete obstruction of the protected drain, port, or perforation 1233 by the bladder tissue 1004.

Similarly, other examples of bladder and/or ureter retention portion configurations shown in Figures 1, 2A, 7A, 17, 18A, 18B, 18C, 19, 20, 21, 22A, 22B, 23A, 23B, 24, 25, 26, 27, 28A, 28B, 29A, 29B, 30, 31, 32A, 32B, 33, 34, 35A, 35B, 36, 37A, 37B, 38A, 38B, 39, 40, and 41 also provide an outer periphery 1002 or protective surface area 1001 or outer region that contacts and supports bladder tissue 1004 or kidney tissue 1003 and may prevent obstruction or obstruction of a protected drainage hole, port, or perforation 133, 1233 located within the protected surface area or inner surface area 1000 of the retention portion. Each of these embodiments will be discussed further below.

8A, 8B, and 9A-9E, an exemplary retention portion 130 for a ureteral or bladder catheter is illustrated that includes multiple helical coils, such as one or more full coils 184 and one or more half or partial coils 183. The retention portion 130 is movable between a contracted position and a deployed position with the multiple helical coils. For example, a generally straight guidewire can be inserted through the retention portion 130 to maintain the retention portion 130 in a generally straight contracted position. When the guidewire is removed, the retention portion 130 can transition to its coiled configuration. In some examples, the coils 183, 184 extend radially and longitudinally from the distal portion 118 of the tube 122. With specific reference to FIGS. 8A and 8B, in an exemplary embodiment, the retention portion 130 includes two full coils 184 and one half coil 183. For example, as shown in FIGS. 8A and 8B, the outer diameter of the full coil 184, indicated by line D1, can be about 18±2 mm, the diameter D2 of the half coil 183 can be about 14 mm±2 mm, and the coiled retention portion 130 can have a height H of about 16±2 mm.

The retention portion 130 can further include one or more drain holes 132, 1232 (e.g., as shown in FIGS. 9A-9E, 10A, and 10E) configured to draw fluid into the interior of the catheter tube 122. In some embodiments, the retention portion 130 can include two, three, four, five, six, seven, eight, or more drain holes 132, 1232, as well as additional holes 110 at the distal tip or end 120 of the retention portion. In some embodiments, the diameter of each of the drain holes 132, 1232 (e.g., as shown in FIGS. 9A-9E, 10A, and 10E) can range from about 0.7 mm to 0.9 mm, and is preferably about 0.83±0.01 mm. In some examples, the diameter of the additional holes 110 (e.g., as shown in FIGS. 9A-9E, 10A, and 10E) at the distal tip or end of the retention portion 130 can range from about 0.165 mm to about 2.39 mm, or from about 0.7 to about 0.97 mm. The distance between adjacent exhaust holes 132, specifically the linear distance between the nearest outer edges of the exhaust holes 132, 1232 when the coil is straightened, can be about 15 mm±2.5 mm, or about 22.5±2.5 mm or more.

9A-9E, in another exemplary embodiment, the distal portion 118 of the drainage lumen 124 proximal to the retention portion 130 defines a straight or curvilinear central axis L. In some examples, at least half or the first coil 183 and the full or second coil 184 of the retention portion 130 extend about the axis A of the retention portion 130. The first coil 183 begins or originates at a point where the tube 122 bends at an angle α ranging from about 15 degrees to about 75 degrees from the central axis L, preferably about 45 degrees, as indicated by the angle α. As shown in FIGS. 9A and 9B, prior to insertion into the body, the axis A can be coextensive with the longitudinal central axis L. In other examples, as shown in FIGS. 9C-9E, prior to insertion into the body, the axis A extends from the central longitudinal axis L and is curved or angled therewith, for example, at an angle β.

In some embodiments, the multiple coils 184 can have the same or different inner and/or outer diameters D and heights H2 between adjacent coils 184. In that case, the outer diameter D1 of each of the coils 184 can range from about 10 mm to about 30 mm. The height H2 between each of the adjacent coils 184 can range from about 3 mm to about 10 mm.

In other embodiments, the retaining portion 130 is configured to be inserted into a tapered portion of the renal pelvis. For example, the outer diameter D1 of the coil 184 can increase toward the distal end 120 of the tube 122, resulting in a helical structure having a tapered or partially tapered configuration. For example, the distal or maximum outer diameter D1 of the tapered helical portion can range from about 10 mm to about 30 mm, corresponding to the dimensions of the renal pelvis, and the outer diameter D1 of each adjacent coil can decrease closer to the proximal end 128 of the retaining portion 130. The overall height H of the retaining portion 130 can range from about 10 mm to about 30 mm.

In some embodiments, the outer diameter D1 of each coil 184 and/or the height H2 between each of the coils 184 can vary in a regular or irregular manner. For example, the outer diameter D1 of the coils or the height H2 between adjacent coils can increase or decrease by a regular amount (e.g., about 10% to about 25% between adjacent coils 184). For example, for a retention portion 130 having three coils (e.g., as shown in Figures 9A and 9B), the outer diameter D2 of the most proximal or first coil 183 can be about 6 mm to about 18 mm, the outer diameter D3 of the middle or second coil 185 can be about 8 mm to about 24 mm, and the outer diameter D13 of the most distal or third coil 187 can be about 10 mm to about 30 mm.

The retention portion 130 may further comprise drainage perforations, holes, or ports 132 disposed on or adjacent to the retention portion 130 and on or through the sidewall 109 of the catheter tube 122 to allow urinary waste to flow from the exterior of the catheter tube 122 to the inner drainage lumen 124 of the catheter tube 122. The location and size of the drainage ports 132 may vary depending on the desired flow rate and configuration of the retention portion 130. The diameter D11 of each of the drainage ports 132 may independently range from about 0.005 mm to about 1.0 mm. The spacing D12 between the nearest edges of each of the drainage ports 132 may independently range from about 1.5 mm to about 5 mm. The drainage ports 132 may be spaced apart in any arrangement, for example, a random, linear, or offset arrangement. In some examples, the drainage ports 132 may be non-circular and may have a surface area of about 0.00002 to 0.79 ^mm2 .

In some embodiments, as shown in FIG. 9A, the exhaust ports 132 are located around the entire outer periphery 72, 1002 or protected surface area 1001 of the sidewall 109 of the catheter tube 122 to increase the amount of fluid that can be drawn into the exhaust lumen 124 (as shown in FIGS. 2, 9A, and 9B). In other embodiments, as shown in FIGS. 9B-9E and 10-10E, the exhaust holes, ports, or perforations 132 are located essentially only on or on the protected or inner surface area 1000 or radially inwardly facing side 1286 of the coil 184 to prevent blockage or obstruction of the exhaust ports 132, 1232, and the outwardly facing side 1288 of the coil may be essentially free of or devoid of exhaust ports 132, 1232. The outer periphery 72, 189, 1002 or protected surface area 1001 or outer region 192 of the helical coil 183, 184, 1280, 1282, 1284 can contact and support the bladder tissue 1004 or kidney tissue 1003 to prevent blockage or obstruction of the protected drainage holes, ports, or perforations 133, 1233 located within the protected or inner surface area 1000 of the helical coil 183, 184, 1280, 1282, 1284. For example, when negative pressure is induced within the ureter and/or renal pelvis, the mucosal tissue of the ureter and/or kidney can be pulled against the retention portion 130 and can occlude some of the drainage ports 134 on the outer periphery 72, 189, 1002 of the retention portion 130. The evacuation ports 133, 1233 located on the radially inward side 1286 of the reservoir structure or on the protected or inner surface area 1000 will not be significantly occluded when such tissue 1003, 1004 contacts the outer periphery 72, 189, 1002 or the protected surface area 1001 or outer region of the retention portion 130. Furthermore, the risk of injury to tissue from pinching or contact with the evacuation ports 132, 133, 1233 or the protected evacuation holes, ports, or perforations 133, 1233 can be reduced or ameliorated.

9C and 9D, another embodiment of a ureteral catheter 112 is illustrated having a retention portion 130 with a plurality of coils 184. As shown in FIG. 9C, the retention portion 130 includes three coils 184 extending about an axis A. The axis A is a curved arc extending from a central longitudinal axis L of a portion of the drainage lumen 181 proximal to the retention portion 130. The curvature imparted to the retention portion 130 can be selected to correspond to the curvature of the renal pelvis, which includes a conical, receptacle-shaped cavity.

9D, in another exemplary embodiment, the retention portion 130 can include two coils 184 extending about an angled axis A. The angled axis A extends at an angle from the central longitudinal axis L and is angled relative to an axis that is generally perpendicular to the central axis L of the drainage lumen portion, as shown by the angle β. The angle β can range from about 15 to about 75 degrees (e.g., from about 105 to about 165 degrees relative to the central longitudinal axis L of the drainage lumen portion of the catheter 112).

Figure 9E shows another embodiment of a ureteral catheter 112. The retention portion comprises three helical coils 184 extending about an axis A. The axis A is angled with respect to the horizontal, as indicated by the angle β. As in the previous embodiment, the angle β can range from about 15 to about 75 degrees (e.g., from about 105 to about 165 degrees relative to the central longitudinal axis L of the drainage lumen portion of the catheter 112).

In some embodiments shown in FIGS. 10-10E, the retention portion 1230 is integral with the tube 1222. In other embodiments, the retention portion 1230 can comprise a separate tubular member that is connected to and extends from the tube or exhaust lumen 1224.

In some embodiments, the retention portion comprises a plurality of radially extending coils 184. The coils 184 are configured in a funnel shape, thereby forming a funnel support. Some examples of coil funnel supports are shown in Figures 2A-C, 7A, 7B, 8A, and 8A-10E.

In some examples, at least one sidewall 119 of the funnel-shaped support comprises at least a first coil 183 having a first diameter and a second coil 184 having a second diameter, the first diameter being less than the second diameter, and a maximum distance between a portion of the sidewall of the first coil and a portion of an adjacent sidewall of the second coil ranges from about 0 mm to about 10 mm. In some examples, the first diameter of the first coil 183 ranges from about 1 mm to about 10 mm, and the second diameter of the second coil 184 ranges from about 5 mm to about 25 mm. In some examples, the diameter of the coils increases toward the distal end of the exhaust lumen, resulting in a helical structure having a tapered or partially tapered configuration. In some embodiments, the second coil 184 is closer to the end of the distal portion 118 of the exhaust lumen 124 than the first coil 183. In some embodiments, the second coil 184 is closer to the end of the proximal portion 128 of the exhaust lumen 124 than the first coil 183.

In some embodiments, at least one sidewall 119 of the funnel-shaped support comprises an inwardly facing side 1286 and an outwardly facing side 1288, as discussed below, where the inwardly facing side 1286 comprises at least one opening 133, 1233 to allow fluid flow into the exhaust lumen, and the outwardly facing side 1288 is essentially free or devoid of openings. In some embodiments, the at least one opening 133, 1233 has an area ranging from about 0.002 mm ² to about 100 mm ² .

In some embodiments, the first coil 1280 comprises a sidewall 119 having a radially inwardly facing side 1286 and a radially outwardly facing side 1288, the radially inwardly facing side 1286 of the first coil 1280 comprising at least one opening 1233 for permitting fluid flow into the exhaust lumen.

In some embodiments, the first coil 1280 comprises a sidewall 119 having a radially inwardly facing side 1286 and a radially outwardly facing side 1288, the radially inwardly facing side 1286 of the first coil 1280 comprising at least two openings 1233 for permitting fluid flow into the exhaust lumen 1224.

In some embodiments, the first coil 1280 comprises a sidewall 119 having a radially inwardly facing side 1286 and a radially outwardly facing side 1288, and the radially outwardly facing side 1288 of the first coil 1280 is essentially free or absent of one or more openings 1232.

In some embodiments, the first coil 1280 comprises a sidewall 119 having a radially inwardly facing side 1286 and a radially outwardly facing side 1288, the radially inwardly facing side 1286 of the first coil 1280 comprising at least one opening 1233 for permitting fluid flow into the exhaust lumen 1224, and the radially outwardly facing side 1288 is essentially free or absent of one or more openings 1232.

10-10E, in some embodiments, the distal portion 1218 comprises an open distal end 1220 for drawing fluid into the drainage lumen 1224. The distal portion 1218 of the ureteral catheter 1212 further comprises a retention portion 1230 for maintaining the distal portion 1218 of the drainage lumen or tube 1222 within the ureter and/or kidney. In some embodiments, the retention portion 1230 comprises a plurality of radially extending coils 1280, 1282, 1284. The retention portion 1230 can be flexible and bendable to allow for positioning of the retention portion 1230 within the ureter, renal pelvis, and/or kidney. For example, the retention portion 1230 is desirably bendable enough to absorb forces exerted on the catheter 1212 and prevent such forces from being transmitted to the ureter. Additionally, when the retention portion 1230 is pulled in a proximal direction P (shown in FIGS. 9A-9E ) toward the patient's bladder 10, the retention portion 1230 can be sufficiently flexible to begin to uncoil or straighten so that it can be pulled through the ureters 6, 8. In some embodiments, the retention portion 1230 is integral with the tube 1222. In other embodiments, the retention portion 1230 can comprise a separate tubular member connected to and extending from the tube or drainage lumen 1224. In some embodiments, the catheter 1212 comprises a radiopaque band 1234 (shown in FIG. 29 ) positioned on the tube 1222 at the proximal end of the retention portion 1230. The radiopaque band 1234 is visible by fluoroscopic imaging during deployment of the catheter 1212. In particular, the user can monitor the advancement of the band 1234 through the urinary tract via fluoroscopy and determine when the retention portion 1230 is within the renal pelvis and ready for deployment.

In some examples, the retention portion 1230 comprises perforations, exhaust ports, or openings 1232 in the sidewall of the tube 1222. As described herein, the location and size of the openings 1232 can vary depending on the desired volumetric flow rate per opening and the size constraints of the retention portion 1230. In some examples, the diameter D11 of each of the openings 1232 can independently range from about 0.05 mm to about 2.5 mm and have an area of about 0.002 mm ² to about 5 mm ^2. The openings 1232 can be positioned to extend along the sidewall 119 of the tube 1222 in any direction desired, such as longitudinally and/or axially. In some examples, the spacing between the nearest adjacent edges of each of the openings 1232 can range from about 1.5 mm to about 15 mm. Fluid passes through one or more of the perforations, exhaust ports, or openings 1232 into the exhaust lumen 1234. Desirably, the openings 1232 are positioned such that they are not occluded by tissue of the ureter 6, 8 or kidney 1003 when negative pressure is applied to the drainage lumen 1224. For example, as described herein, the openings 1233 can be positioned on an interior portion or protected surface area 1000 of the coil or other structure of the retention portion 1230 to avoid occlusion of the openings 1232, 1233. In some examples, the central portion 1226 and the proximal portion 1228 of the tube 1222 are essentially free or devoid of perforations, ports, openings, or apertures to avoid occlusion of the openings along those portions of the tube 1222. In some examples, the portions 1226, 1228 that are essentially devoid of perforations or openings include substantially fewer openings 1232 than other portions, such as the distal portion 1218 of the tube 1222. For example, the total area of the openings 1232 in the distal portion 1218 may be greater than or substantially greater than the total area of the openings in the central portion 1226 and/or proximal portion 1228 of the tube 1222.

In some embodiments, the openings 1232 are sized and spaced to improve fluid flow through the retention portion 1230. In particular, the inventors have discovered that when negative pressure is applied to the drain lumen 1224 of the catheter 1212, a majority of the fluid is drawn into the drain lumen 1224 through the proximal-most perforation or opening 1232. Larger size or greater number of openings 1232 can be provided toward the distal end 1220 of the retention portion 1230 to improve flow dynamics such that fluid is also received through more distal openings and/or through the open distal end 1220 of the tube 1222. For example, the total area of the openings 1232 on the length of the tube 1222 near the proximal end 1228 of the retention portion 1230 may be less than the total area of the openings 1232 of a similarly sized length of the tube 1222 located near the open distal end 1220 of the tube 1222. In particular, it may be desirable to produce a flow distribution through the exhaust lumen 1224 in which less than 90%, preferably less than 70%, and more preferably less than 55% of the fluid flow is withdrawn through a single opening 1232 or a small number of openings 1232 positioned in the exhaust lumen 1224 near the proximal end 1228 of the retention portion 1230.

In many embodiments, the opening 1232 is generally circular in shape, although triangles, ovals, squares, diamonds, and any other opening shapes may also be used. Additionally, as will be appreciated by one skilled in the art, the shape of the opening 1232 may change as the tube 1222 transitions between the uncoiled or extended position and the coiled or deployed position. It should be noted that while the shape of the opening 1232 may vary (e.g., the orifice may be circular in one position and slightly extended in another), the area of the opening 1232 is substantially similar in the extended or uncoiled position as compared to the deployed or coiled position.

In some embodiments, the drainage lumen 1224 defined by the tube 1222 comprises a distal portion 1218 (e.g., a portion of the tube 1222 configured to be positioned within the ureters 6, 8 and renal pelvis 20, 21 (e.g., as shown in FIGS. 7A and 10 ), a middle portion 1226 (e.g., a portion of the tube 1222 configured to extend from the distal portion through the ureteral orifice 16 into the patient's bladder 10 and urethra 12 (e.g., as shown in FIGS. 7A and 10 ), and a proximal portion 1228 (e.g., a portion of the tube 1222 extending from the urethra 12 to an external fluid collection container and/or pump 2000). In one embodiment, the combined length of the proximal portion 1228 and the middle portion 1226 of the tube 1222 is about 54±2 cm. In some embodiments, the central portion 1226 and the proximal portion 1228 of the tube 1222 include distance markings 1236 (shown in FIG. 10 ) on the sidewalls of the tube 1222, which can be used to determine the distance the tube 1222 has been inserted into the patient's urinary tract during deployment of the catheter 1212.

As shown in Figures 7A and 10-14, the exemplary ureteral catheter 1212 comprises at least one elongate body or tube 1222, the interior of which defines or comprises one or more drainage channels or lumens, such as a drainage lumen 1224. The tube 1222 size can range from about 1 Fr to about 9 Fr (French catheter scale). In some examples, the tube 1222 can have an outer diameter ranging from about 0.33 to about 3.0 mm and an inner diameter ranging from about 0.165 to about 2.39 mm. In one example, the tube 1222 is 6 Fr and has an outer or outside diameter of 2.0 ± 0.1 mm. The overall length of the tube 1222 can range from about 30 cm to about 120 cm, depending on the age (e.g., pediatric or adult) and gender of the patient.
The tube 1222 can be formed from a flexible and/or deformable material to facilitate advancement and/or positioning of the tube 1222 within the bladder 10 and ureters 6, 8 (shown in FIG. 7), such as any of the materials discussed above. For example, the tube 1222 can be formed from one or more materials, such as a biocompatible polymer, polyvinyl chloride, polytetrafluoroethylene (PTFE) such as Teflon®, silicone coated latex, or silicone. In one example, the tube 1222 is formed from a thermoplastic polyurethane.
Spiral coil retention part

10A-10E, an exemplary retention portion 1230 comprises a helical coil 1280, 1282, 1284. In some embodiments, the retention portion 1230 comprises a first or half coil 1280 and two full coils, such as a second coil 1282 and a third coil 1284. As shown in FIG. 10A-10D, in some embodiments, the first coil 1280 comprises a half coil that extends from 0 degrees to 180 degrees around a curvilinear central axis A of the retention portion 1230. In some embodiments, as shown, the curvilinear central axis A is generally straight and coextensive with the curvilinear central axis of the tube 1222. In other embodiments, the curvilinear central axis A of the retention portion 1230 can be curved to impart a container shape to the retention portion 1230, for example, a conical shape. The first coil 1280 can have a diameter D1 of about 1 mm to 20 mm, preferably about 8 mm to 10 mm. The second coil 1282 can be a full coil extending 180 degrees to 540 degrees along the retention portion 1230 with a diameter D2 of about 5 mm to 50 mm, preferably about 10 mm to 20 mm, more preferably about 14 mm ± 2 mm. The third coil 1284 can be a full coil extending 540 degrees to 900 degrees and with a diameter D3 of 5 mm and 60 mm, preferably about 10 mm to 30 mm, more preferably about 18 mm ± 2 mm. In other embodiments, the multiple coils 1282, 1284 can have the same inner and/or outer diameter. For example, the outer diameter of each of the full coils 1282, 1284 can be about 18 ± 2 mm.

In some embodiments, the overall height H of the retention portion 1230 ranges from about 10 mm to about 30 mm, preferably about 18±2 mm. The height H2 of the gap between adjacent coils 1284, i.e., between the sidewall 1219 of the tube 1222 of the first coil 1280 and the adjacent sidewall 1221 of the tube 122 of the second coil 1282, is less than 3.0 mm, preferably about 0.25 mm to 2.5 mm, more preferably about 0.5 mm to 2.0 mm.

The retaining portion 1230 can further include a distal-most curved portion 1290. For example, the distal-most portion 1290 of the retaining portion 1230, including the open distal end 1220 of the tube 1222, can be curved inward relative to the curvature of the third coil 1284. For example, the curvilinear central axis X1 (shown in FIG. 10D) of the distal-most portion 1290 can extend from the distal end 1220 of the tube 1222 toward the curvilinear central axis A of the retaining portion 1230.

The retention portion 1230 is movable between a contracted position, in which the retention portion 1230 is straight for insertion into the patient's urinary tract, and a deployed position, in which the retention portion 1230 comprises helical coils 1280, 1282, 1284. Generally, the tube 1222 is naturally biased toward the coiled configuration. For example, a non-coiled or generally straight guidewire can be inserted through the retention portion 1230 to maintain the retention portion 1230 in its straight contracted position, as shown, for example, in FIGS. 11-14. When the guidewire is removed, the retention portion 1230 naturally transitions to its coiled position.

In some embodiments, the openings 1232, 1233 are located essentially only or only on the radially inwardly facing side 1286 or protected or inner surface area 1000 of the coils 1280, 1282, 1284 to prevent blockage or obstruction of the openings 1232, 1233. The radially outwardly facing side 1288 of the coils 1280, 1282, 1284 may be essentially free of openings 1232. In similar embodiments, the total area of the openings 1232, 1233 on the inwardly facing side 1286 of the retention portion 1230 may be substantially greater than the total area of the openings 1232 on the radially outwardly facing side 1288 of the retention portion 1230. Thus, when negative pressure is induced within the ureter and/or renal pelvis, ureteral and/or renal mucosal tissue may be pulled against the retention portion 1230 and may occlude some openings 1232 on the outer periphery 1002 or protected surface area 1001 of the retention portion 1230. However, openings 1232 located on the radially inwardly facing side 1286 or protected or inner surface area 1000 of the retention portion 1230 are not significantly occluded when such tissue contacts the outer periphery 1002 or protected surface area 1001 of the retention portion 1230. Thus, the risk of tissue injury from entrapment or contact with the drainage openings 1232 can be reduced or eliminated.
Hole or opening distribution example

In some embodiments, the first coil 1280 can be free of or essentially free of openings 1232. For example, the total area of the openings 1232 on the first coil 1280 can be less than or substantially less than the total area of the openings 1232 on the complete coils 1282, 1284. Examples of various arrangements of apertures or openings 1232 that can be used for a coiled retention portion (such as the coiled retention portion 1230 shown in FIGS. 10A-10E) are illustrated in FIGS. 11-14. As shown in FIGS. 11-14, the retention portion 1330 is depicted in its uncoiled or straight position, as occurs when a guidewire is inserted through the drainage lumen.

An exemplary retention portion 1330 is illustrated in FIG. 11. To more clearly illustrate the positioning of the openings in the retention portion 1330, the retention portion 1330 is referred to herein as being divided into multiple sections or perforated sections, such as a proximal-most or first section 1310, a second section 1312, a third section 1314, a fourth section 1316, a fifth section 1318, and a distal-most or sixth section 1320. One of ordinary skill in the art will appreciate that fewer or additional sections can be included as desired. As used herein, "section" refers to a discrete length of the tube 1322 within the retention portion 1330. In some embodiments, the sections are equal in length. In other embodiments, some sections can have the same length and other sections can have different lengths. In other embodiments, each section has a different length. For example, sections 1310, 1312, 1314, 1316, 1318, and 1320 can each have a length L1-L6 that ranges from about 5 mm to about 35 mm, preferably from about 5 mm to 15 mm.

In some examples, each of the sections 1310, 1312, 1314, 1316, 1318, and 1320 includes one or more openings 1332. In some examples, each of the sections includes a single opening 1332. In other examples, the first section 1310 includes a single opening 1332, and the other sections include multiple openings 1332. In other examples, different sections include one or more openings 1332, and the openings each have a different shape or a different total area.

In some embodiments, such as the retention portion 1230 shown in Figures 10A-10E, the first or half coil 1280, which extends from 0 to about 180 degrees of the retention portion 1230, can be free of or essentially free of openings. The second coil 1282 can include a first section 1310, which extends from about 180 to 360 degrees. The second coil 1282 can also include second and third sections 1312, 1314, which are positioned from about 360 to 540 degrees of the retention portion 1230. The third coil 1284 can include fourth and fifth sections 1316, 1318, which are positioned from about 540 to 900 degrees of the retention portion 1230.

In some embodiments, the openings 1332 can be sized such that the total area of the openings in the first section 1310 is less than the total area of the openings in the adjacent second section 1312. Similarly, if the retention portion 1330 further comprises a third section 1314, the openings in the third section 1314 can have a total area that is greater than the total area of the openings in the first section 1310 or the second section 1312. The openings in the fourth section 1316, the fifth section 1318, and the sixth section 1320 can also have gradually increasing total areas and/or numbers of openings to improve fluid flow through the tube 1222.

11, the tube retention portion 1230 includes five sections 1310, 1312, 1314, 1316, 1318, each including a single opening 1332, 1334, 1336, 1338, 1340. The retention portion 1330 also includes a sixth section 1320, which includes the open distal end 1220 of the tube 1222. In this example, the openings 1232 of the first section 1310 have a minimum total area. For example, the total area of the openings 1332 of the first section can range from about 0.002 mm ² to about 2.5 mm ² , or from about 0.01 mm ² to 1.0 mm ² , or from about 0.1 mm ² to 0.5 mm ² . In one example, the opening 1332 is about 55 mm from the distal end 1220 of the catheter and has a diameter of 0.48 mm and an area of 0.18 ^mm2 . In this example, the total area of the openings 1334 in the second section 1312 exceeds the total area of the openings 1232 in the first section 1310 and can range in size from about 0.01 ^mm2 to about ^1.0 mm2. The third opening 1336, fourth opening 1338, and fifth opening 1350 can also range in size from about 0.01 ^mm2 to about ^1.0 mm2. In one example, the second opening 1334 is about 45 mm from the distal end of the catheter 1220 and has a diameter of about 0.58 mm and an area of about 0.27 ^mm2 . The third opening 1336 is about 35 mm from the distal end of the catheter 1220 and can have a diameter of about 0.66 mm. The fourth opening 1338 can be about 25 mm from the distal end 1220 and have a diameter of about 0.76 mm. The fifth opening 1340 can be about 15 mm from the distal end 1220 of the catheter and have a diameter of about 0.889 mm. In some embodiments, the open distal end 1220 of the tube 1222 has a maximum opening having an area ranging from about 0.5 mm ² to about 5.0 mm ² or greater. In one embodiment, the open distal end 1220 has a diameter of about 0.97 mm and an area of about 0.74 mm ² .

As described herein, the openings 1332, 1334, 1336, 1338, 1340 can be positioned and sized such that when negative pressure is applied to the exhaust lumen 1224 of the catheter 1212, e.g., from the proximal portion 1228 of the exhaust lumen 1224, the volumetric flow rate of fluid passing through the first opening 1332 more closely corresponds to the volumetric flow rate of the openings of the more distal sections. As described above, if each opening is of the same area, when negative pressure is applied to the exhaust lumen 1224, the volumetric flow rate of fluid passing through the proximal-most first opening 1332 will substantially exceed the volumetric flow rate of fluid passing through the openings 1334 closer to the distal end 1220 of the retention portion 1330. Without intending to be bound by any theory, it is believed that when negative pressure is applied, the pressure differential between the interior of the exhaust lumen 1224 and the exterior of the exhaust lumen 1224 is greater in the region of the most proximal opening and decreases at each opening moving toward the distal end of the tube. For example, the size and location of the openings 1332, 1334, 1336, 1338, 1340 can be selected such that the volumetric flow rate for fluid flowing into the openings 1334 of the second section 1312 is at least about 30% of the volumetric flow rate of fluid flowing into the openings 1332 of the first section 1310. In other examples, the volumetric flow rate for fluid flowing into the most proximal or first section 1310 is less than about 60% of the total volumetric flow rate for fluid flowing through the proximal portion of the exhaust lumen 1224. In other examples, the volumetric flow rate for fluid flowing into the openings 1332, 1334 of the two most proximal sections (e.g., the first section 1310 and the second section 1312) can be less than about 90% of the volumetric flow rate of fluid flowing through the proximal portion of the exhaust lumen 1224 when a negative pressure, e.g., a negative pressure of about -45 mmHg, is applied to the proximal end of the exhaust lumen.

As will be appreciated by those skilled in the art, the volumetric flow rate and distribution for a catheter or tube with multiple openings or perforations can be directly measured or calculated in a variety of different ways. As used herein, "volume flow rate" refers to the actual measurement of the volumetric flow rate downstream and adjacent to each opening or the use of the methods for "calculated volumetric flow rate" described below.

For example, actual measurements of fluid volume dispersed over time can be used to determine the volumetric flow rate through each opening 1332, 1334, 1336, 1338, 1340. In one exemplary experimental arrangement, a multi-chamber container with individual chambers sized to receive sections 1310, 1312, 1314, 1316, 1318, 1320 of retention portion 1330 can be sealed around and enclosing retention portion 1330. Each opening 1332, 1334, 1336, 1338, 1340 can be sealed within one of the chambers. The amount of fluid volume drawn through each opening 1332, 1334, 1336, 1338, 1340 from the individual chambers into tube 3222 can be measured to determine the amount of fluid volume drawn into each opening over time when negative pressure is applied. The cumulative amount of fluid volume collected in tube 3222 by the negative pressure pump system will be equal to the sum of the fluid drawn into each opening 1332, 1334, 1336, 1338, 1340.

Alternatively, the volumetric fluid flow rates through the different openings 1332, 1334, 1336, 1338, 1340 can be mathematically calculated using equations to model fluid flow through the tubular body. For example, the volumetric flow rates of fluid passing through the openings 1332, 1334, 1336, 1338, 1340 into the exhaust lumen 1224 can be calculated based on a mass transfer shell balance evaluation, as described in detail below in connection with mathematical examples and Figures 15A-15C. Steps for deriving the mass balance equations and calculating the flow distribution between or volumetric flow rates related to the openings 1332, 1334, 1336, 1338, 1340 are also described in detail below in connection with Figures 15A-15C.

Another exemplary retention portion 2230 with openings 2332, 2334, 2336, 2338, 2340 is illustrated in FIG. 12. As shown in FIG. 12, the retention portion 2230 includes multiple smaller perforations or openings 2332, 2334, 2336, 2338, 2340. Each of the openings 2332, 2334, 2336, 2338, 2340 can have substantially the same cross-sectional area, or one or more of the openings 2332, 2334, 2336, 2338, 2340 can have different cross-sectional areas. As shown in FIG. 12, the retention portion 2330 includes six sections 2310, 2312, 2314, 2316, 2318, 2320 as described above, with each section including a plurality of openings 2332, 2334, 2336, 2338, 2340. In the example shown in FIG. 12, the number of openings 2332, 2334, 2336, 2338, 2340 per section increases toward the distal end 2220 of the tube 2222 such that the total area of the openings 1332 in each section increases compared to the proximally adjacent sections.

12, the openings 2332 of the first section 2310 are aligned along a first imaginary line V1 that is generally parallel to the curvilinear central axis X1 of the retention portion 2230. The openings 2334, 2336, 2338, 2340 of the second section 2312, the third section 2314, the fourth section 2316, and the fifth section 2318 are positioned on the sidewall of the tube 2222 in an increasing number of rows such that the openings 2334, 2336, 2338, 2340 of these sections are also aligned around the circumference of the tube 2222. For example, some of the openings 2334 of the second section 2312 are positioned such that a second imaginary line V2 extending around the circumference of the sidewall of the tube 2222 contacts at least a portion of the plurality of openings 2334. For example, the second section 2312 can include two or more rows of perforations or openings 2334, with each opening 2334 having an equal or different cross-sectional area. Additionally, in some embodiments, at least one of the rows of the second section 2312 can be aligned along a third imaginary line V3 that is parallel to the curvilinear central axis X1 of the tube 2222, but is not coextensive with the first imaginary line V1. Similarly, the third section 2314 can include five rows of perforations or openings 2336, with each opening 2336 having an equal or different cross-sectional area, the fourth section 2316 can include seven rows of perforations or openings 2338, and the fifth section 2318 can include nine rows of perforations or openings 2340. As in the previous embodiments, the sixth section 2320 includes a single opening, i.e., the open distal end 2220 of the tube 2222. In the embodiment of FIG. 12, each of the openings has the same area, however, the area of one or more of the openings may vary, as desired.

Another exemplary retention portion 3230 with openings 3332, 3334, 3336, 3338, 3340 is illustrated in FIG. 13. The retention portion 3230 of FIG. 13 includes a plurality of similarly sized perforations or openings 3332, 3334, 3336, 3338, 3340. As in the previous example, the retention portion 3230 can be divided into six sections 3310, 3312, 3314, 3316, 3318, 3320, each with at least one opening. The most proximal or first section 3310 includes one opening 3332. The second section 3312 includes two openings 3334 that are aligned along an imaginary line V2 that extends around the circumference of the sidewall of the tube 3222. The third section 3314 includes a group of three openings 3336 that are located at the vertices of an imaginary triangle. The fourth section 3316 includes a group of four openings 3338 positioned at the corners of an imaginary square. The fifth section 3318 includes ten openings 3340 positioned to form a diamond shape on the sidewall of the tube 3222. As in the previous example, the sixth section 3320 includes a single opening, i.e., the open distal end 3220 of the tube 3222. The area of each opening can range from about 0.001 mm ² to about 2.5 mm ^2. In the example of FIG. 13, the openings each have the same area, although the area of one or more openings can vary, as desired.

Another exemplary retention portion 4230 with openings 4332, 4334, 4336, 4338, 4340 is illustrated in FIG. The openings 4332, 4334, 4336, 4338, 4340 of the retention portion 4330 have different shapes and sizes. For example, the first section 4310 includes a single circular opening 4332. The second section 4312 has a circular opening 4334 with a larger cross-sectional area than the opening 4332 of the first section 4310. The third section 4314 includes three triangular openings 4336. The fourth section 4316 includes a large circular opening 4338. The fifth section 4318 includes a diamond shaped opening 4340. As in the previous example, the sixth section 4320 includes the open distal end 4220 of the tube 4222. 14 illustrates one example of an arrangement of different shaped openings within each section. It should be understood that the shape of each opening within each section can be independently selected, for example, first section 4310 can have one or more diamond shaped openings or other shapes. The area of each opening can be the same or different and can range from about 0.001 ^mm2 to about 2.5 ^mm2 .

Calculation of Volume Flow Rate and Percentage of Flow Distribution Having described the various arrangements of openings for the retention portion of the ureteral catheter 1212, the method for determining the calculated percentage of flow distribution and the calculated volume flow rate through the catheter will now be described in detail. A schematic diagram of an exemplary catheter is shown in FIG. 16 with sidewall openings indicating the location of the portions of the tube or drainage lumen used in the following calculations. The calculated percentage of flow distribution refers to the percentage of the total fluid flowing through the proximal portion of the drainage lumen that enters the drainage lumen through different openings or sections of the retention portion. The calculated volume flow rate refers to the fluid flow rate per unit time through the different portions of the drainage lumen or openings of the retention portion. For example, the volume flow rate for the proximal portion of the drainage lumen describes the flow rate for the total amount of fluid passing through the catheter. The volume flow rate for the openings refers to the volume of fluid passing through the openings into the drainage lumen per unit time. In Tables 3-5 below, flow is described as a percentage of the total fluid flow rate or total volumetric flow rate for the proximal portion of the exhaust lumen. For example, an opening with a 100% flow distribution would mean that all fluid entering the exhaust lumen passed through the opening. An opening with a 0% distribution would indicate that no fluid in the exhaust lumen entered the exhaust lumen through that opening.

These volumetric flow rate calculations were used to determine and model the fluid flow rate through the retention portion 1230 of the ureteral catheter 1212 shown in Figures 7A and 10-10E. Furthermore, these calculations show that adjusting the area of the openings and the linear distribution of the openings along the retention portion results in a distribution of fluid flow through the different openings. For example, reducing the area of the most proximal opening reduces the percentage of fluid drawn into the catheter through the most proximal opening and increases the percentage of fluid drawn into the more distal openings of the retention portion.

For the following calculations, a tubing length of 86 cm was used with an inner diameter of 0.97 mm and an end hole inner diameter of 0.97 mm. The density of urine was 1.03 g/mL with a friction coefficient μ of 8.02×10−3 Pa·S (8.02×10−3 kg/s·m) at 37° C. The volumetric flow rate of urine passing through the catheter was 2.7 ml/min (Q _Total ), as determined by experimental measurements.

The calculated volumetric flow rate is determined by a volumetric mass balance equation in which the sum of the volumetric flows through all perforations or openings 1232 in the five sections of the retention portion (referred to herein as volumetric flow rates Q ₂ -Q ₆ ) and through the open distal end 1220 (referred to herein as volumetric flow rate Q ₁ ) is equal to the total volumetric flow (Q _Total ) exiting the proximal end of the tube 1222 a distance between 10 cm and 60 cm away from the last proximal opening, as shown in Equation 2.
Q _Total = Q ₁ + Q ₂ + Q ₃ + Q ₄ + Q ₅ + Q ₆ (Equation 2)

The modified loss coefficients (K') for each section are based on three types of loss coefficients in the catheter model: an inlet loss coefficient that accounts for the resulting pressure loss at the pipe inlet (e.g., the opening and open distal end of tube 1222), a friction loss coefficient that accounts for the pressure loss resulting from friction between the fluid and the pipe wall, and a flow merging loss coefficient that accounts for the pressure loss resulting from the interaction of the two flows together.

The entrance loss coefficient depends on the shape of the orifice or opening. For example, a tapered or nozzle-shaped orifice will increase the flow rate into the exhaust lumen 1224. Similarly, a sharp-edged orifice will have a different flow quality than an orifice with an ill-defined edge. For purposes of the following calculations, the opening 1232 is assumed to be a side orifice opening and the open distal end 1220 of the tube 1222 is assumed to be a sharp-edged opening. The cross-sectional area of each opening is considered constant through the tube sidewall.

The friction loss coefficient approximates the pressure loss resulting from friction between the fluid and the adjacent interior wall of the tube 1222. The friction loss is defined according to the following equation:

The flow joining loss coefficients are derived from the loss coefficients for combining flows at a 90 degree branching angle. Values for the loss coefficients were taken from Charts 13.10 and 13.11 of Miller DS, Internal Flow Systems, 1990, incorporated herein by reference. The charts use the ratio of the inlet orifice area (referred to as A1 on the chart) to the pipe cross-sectional area (referred to as A3 on the chart) and the ratio of the inlet orifice volumetric flow rate (Q1 on the chart) to the resulting combined pipe volumetric flow rate (Q3 on the chart). For example, for an area ratio of 0.6 between the area of the opening and the area of the discharge lumen, the following flow joining loss coefficients ( _K13 and _K23 ) would be used:

To calculate the total manifold loss factor (K), it is necessary to separate the model into so-called "reference stations" and gradually process and equilibrate the pressure and flow distribution of the two paths (e.g., flow through the opening and flow through the exhaust lumen of the tube), starting from the distal tip of the most proximal "station" and reaching each station. A graphical representation of the different stations used for this calculation is shown in FIG. 16. For example, the most distal "station" A is the distal open end 1220 of the tube 122. The second station A' is the most distal opening on the side wall of the tube 122 (e.g., the opening of the fifth section 1318 in FIG. 11-14). The next station B is for flow through the exhaust lumen 1224 just proximal to the A' opening.

To calculate the loss between station A (the distal opening) and station B for fluid entering through the open distal end (path 1) of tube 1222, the modified loss coefficient (K') is equal to:

Similarly, the second path to station B is through opening 1334 in fifth section 1318 (shown in FIGS. 11-14) of retention portion 1330. The revised loss calculation for path 2 is calculated as follows:

The modified loss coefficients for both paths 1 and 2 must be equalized to ensure that the volumetric flow rates ( _Q1 and _Q2 ) reflect the equilibrium distribution in the manifold at station B. The volumetric flow rates are adjusted until equal modified loss coefficients for both paths are achieved. The volumetric flow rates can be adjusted to represent some fractional portion of the total volumetric flow rate (Q' _Total ), which is assumed to be unity for purposes of this stepwise solution. Upon equalizing the two modified loss coefficients, one can then proceed to equalize the two paths to reach station C (fourth section 1316 in FIG. 11-14).

The loss coefficient between station B (flow through the exhaust lumen in fifth section 1318) and station C (flow through the lumen in fourth section 1316) is calculated in a similar manner, as shown by equations 5.1 and 5.2. For example, for path 1 (station B to station C), the modified loss coefficient (K') for the opening of fourth section 1316 is defined as follows:

For path 2 (station B to C), the modified loss coefficient (K') based on the flow area of the opening of the fourth section 1316 is defined as follows:

As with the previous stations, the modified loss coefficients for both path 1 and path 2 must be equalized to ensure that the volumetric flow rates ( _Q1 , _Q2 , and _Q3 ) reflect the equilibrium distribution within the manifold up to station C. Depending on the equalization of the two modified loss coefficients, one can then proceed to equalize the two paths to arrive at station D, station E, and station F. The step-wise solution process proceeds through each station, as demonstrated, until calculating the modified loss coefficient for the final station, in this case station F. The total loss coefficient (K) for the manifold can then be calculated using the actual _QTotal (volume flow rate through the proximal portion of the exhaust lumen) determined through experimental measurements.

The fractional volumetric flow rate calculated through the stepwise run can then be multiplied by the actual total volumetric flow rate (Q _Total ) to determine the flow rate through each opening 1232 (shown in FIGS. 10-10E) and the open distal end 1220 .

Examples of calculated volumetric flow rates are provided below and shown in Tables 3-5 and Figures 15A-15C.

Example 1
Example 1 illustrates the fluid flow distribution of retention member tubes with different sized openings, corresponding to the embodiment of retention member 1330 shown in Figure 11. As shown in Table 3, the most proximal opening (Q6) had a diameter of 0.48 mm, the most distal opening (Q5) on the side wall of the tube had a diameter of 0.88 mm, and the open distal end of the tube (Q6) had a diameter of 0.97 mm. Each of the openings was circular.

The flow distribution and calculated volumetric flow rate percentages were determined as follows:

To calculate the flow distribution for each "station" or opening, the calculated K' value was multiplied by the actual total volumetric flow rate (Q _Total ) to determine the flow rate through each perforation and the distal hole. Alternatively, the calculated results can be presented as a percentage of the total flow rate or flow distribution, as shown in Table 3. As shown in Table 3 and FIG. 15C, the percentage of flow distribution (% Flow Distribution) through the most proximal opening (Q6) was 56.1%. The flow rate through the two most proximal openings (Q6 and Q5) was 84.6%.

As demonstrated in Example 1, increasing the diameter of the perforations progressing from the proximal to the distal region of the retention portion of the tube results in more evenly distributed flow across the entire retention portion.

Example 2
In Example 2, each opening has the same diameter and area. As shown in Table 4 and FIG. 15A, the flow distribution through the most proximal opening is then 86.2% of the total flow through the tube. The flow distribution through the second opening is 11.9%. Therefore, in this example, it was calculated that 98.1% of the fluid passing through the drainage lumen entered the lumen through the two most proximal openings. Compared to Example 1, Example 2 increased the flow rate through the proximal end of the tube. Thus, Example 1 provides a wider flow distribution in which a larger percentage of the fluid enters the drainage lumen through openings other than the most proximal opening. Thus, fluid is more efficiently collected through multiple openings, which can reduce fluid stagnation and improve the distribution of negative pressure through the renal pelvis and/or kidney.

Example 3
Example 2 also illustrates the flow distribution for orifices having the same diameter. However, as shown in Table 5, the orifices are closer together (10 mm vs. 22 mm). As shown in Table 5 and FIG. 15B, 80.9% of the fluid passing through the exhaust lumen entered the exhaust lumen through the most proximal orifice (Q6). 96.3% of the fluid in the exhaust lumen entered the exhaust lumen through the two most proximal orifices (Q5 and Q6).

17-41C, and more specifically, FIG. 17, two exemplary ureteral catheters 5000, 5001 and bladder catheter 116 are shown positioned within a patient's urinary tract. The ureteral catheters 5000, 5001 include drainage lumens 5002, 5003 for draining fluids, such as urine, from at least one of the patient's kidneys 2, 4, renal pelvis 20, 21, or ureters 6, 8 adjacent the renal pelvis 20, 21. The drainage lumens 5002, 5003 include distal portions 5004, 5005 configured to be positioned within the patient's kidneys 2, 4, renal pelvis 20, 21, and/or ureters 6, 8 adjacent the renal pelvis 20, 21, and proximal portions 5006, 5007 through which fluids 5008 drain into the patient's bladder 10 or outside the body, as shown in FIGS. 2B and 2C.

In some embodiments, the distal portion 5004, 5005 comprises an open distal end 5010, 5011 for drawing fluid into the drainage lumen 5002, 5003. The distal portion 5004, 5005 of the ureteral catheter 5000, 5001 further comprises a retaining portion 5012, 5013 for maintaining the distal portion 5004, 5005 of the drainage lumen or tube 5002, 5003 within the ureter and/or kidney. The retaining portion 5012, 5013 can be flexible and/or bendable to allow positioning of the retaining portion 5012, 5013 within the ureter, renal pelvis, and/or kidney. For example, the retaining portion 5012, 5013 is desirably bendable enough to absorb forces exerted on the catheter 5000, 5001 and prevent such forces from being transmitted to the ureter. Additionally, when the retention portions 5012, 5013 are pulled in a proximal direction P (shown in FIG. 17) toward the patient's bladder 10, the retention portions 5012, 5013 can be sufficiently flexible to begin to uncoil, straighten, or collapse so that they can be withdrawn through the ureters 6, 8.

In some embodiments, the retention portion comprises a funnel-shaped support. Non-limiting examples of different shapes of funnel-shaped supports are shown in Figures 7A, 7B, 17, and 18A-41C, which are discussed in detail below. Generally, the funnel-shaped support comprises at least one sidewall. The at least one sidewall of the funnel-shaped support comprises a first diameter and a second diameter, the first diameter being less than the second diameter. The second diameter of the funnel-shaped support is closer to the end of the distal portion of the drainage lumen than the first diameter.

The proximal portion of the drain lumen or drain tube is essentially free or devoid of openings. While not intending to be bound by any theory, it is believed that openings in the drain lumen or drain tube may be undesirable because when negative pressure is applied to the proximal end of the proximal portion of the drain lumen, such openings may reduce the negative pressure at the distal portion of the ureteral catheter, thereby reducing the withdrawal or flow of fluid or urine from the kidney and renal pelvis of the kidney. It is desirable that the flow of fluid from the ureter and/or kidney is not impeded by the obstruction of the ureter and/or kidney by the catheter. Also, while not intending to be bound by any theory, it is believed that when negative pressure is applied to the proximal end of the proximal portion of the drain lumen, the ureteral tissue may be drawn against or into the openings along the proximal portion of the drain lumen, which may inflame the tissue.

Some examples of ureteral catheters with retention portions that include funnel-shaped supports according to the present invention are shown in Figures 7A, 7B, 17, and 18A-41C. In Figures 7A-10E, the funnel-shaped supports are formed by coils of tubing. In Figures 17-41C, other examples of funnel-shaped supports are shown. Each of these funnel-shaped supports according to the present invention will be discussed in detail below.

18A-D, in some embodiments, a distal portion 5004 of a ureteral catheter is shown, generally designated as 5000. The distal portion 5004 includes a retention portion 5012 that constitutes a funnel-shaped support 5014. The funnel-shaped support 5014 includes at least one sidewall 5016. As shown in FIGS. 18C and 18D, the outer periphery 1002 or protected surface area 1001 includes the outer surface or outer wall 5022 of the funnel-shaped support 5014. One or more drainage holes, ports, or perforations, or internal openings 5030 are disposed on the protected or inner surface area 1000 of the funnel-shaped support 5014. As shown in FIGS. 18C and 18D, there is a single drainage hole 5030 at the base portion 5024 of the funnel-shaped support, although multiple holes may be present.

At least one sidewall 5016 of the funnel-shaped support 5014 has a first (outer) diameter D4 and a second (outer) diameter D5, the first outer diameter D4 being less than the second outer diameter D5. The second outer diameter D5 of the funnel-shaped support 5014 is closer to the distal end 5010 of the distal portion 5004 of the exhaust lumen 5002 than the first outer diameter D4. In some embodiments, the first outer diameter D4 can range from about 0.33 mm to about 4 mm (about 1 Fr to about 12 Fr (French catheter scale)) or about 2.0±0.1 mm. In some embodiments, the second outer diameter D5 is greater than the first outer diameter D4 and can range from about 1 mm to about 60 mm, or about 10 mm to 30 mm, or about 18 mm±2 mm.

In some embodiments, at least one sidewall 5016 of the funnel-shaped support 5014 can further include a third diameter D7 (shown in FIG. 18B), the third diameter D7 being less than the second outer diameter D5. The third diameter D7 of the funnel-shaped support 5014 is closer to the distal end 5010 of the distal portion 5004 of the exhaust lumen 5002 than the second diameter D5. The third diameter D7 is discussed in more detail below with respect to the periphery. In some embodiments, the third diameter D7 can range from about 0.99 mm to about 59 mm or from about 5 mm to about 25 mm.

At least one sidewall 5016 of the funnel-shaped support 5014 includes a first (inner) diameter D6. The first inner diameter D6 is closer to the proximal end 5017 of the funnel-shaped support 5014 than the third diameter D7. The first inner diameter D6 is less than the third diameter D7. In some examples, the first inner diameter D6 can range from about 0.05 mm to 3.9 mm or about 1.25±0.75 mm.

In some embodiments, the overall height H5 of the sidewall 5016 along the central axis 5018 of the retention portion 5012 can range from about 1 mm to about 25 mm. In some embodiments, the height H5 of the sidewall can vary in different portions of the sidewall, for example, if the sidewall has wavy or rounded edges as shown in FIG. 24. In some embodiments, the wavy portions can range from about 0.01 mm to about 5 mm or more, as desired.

In some embodiments, the funnel-shaped support 5014 can have a generally conical shape, as shown in Figures 7A-10E and 17-41C. In some embodiments, the angle 5020 between the outer wall 5022 near the proximal end 5017 of the funnel-shaped support 5014 and the exhaust lumen 5002 adjacent the base portion 5024 of the funnel-shaped support 5014 can range from about 100 degrees to about 180 degrees, or from about 100 degrees to about 160 degrees, or from about 120 degrees to about 130 degrees. The angle 5020 may vary at different locations around the circumference of the funnel-shaped support 5014, as shown in Figure 22A, where the angle 5020 ranges from about 140 degrees to about 180 degrees.

In some embodiments, the edge or margin 5026 of the distal end 5010 of at least one sidewall 5016 can be rounded, square, or any shape desired. The shape defined by the edge 5026 can be, for example, circular (as shown in FIGS. 18C and 23B), oval (as shown in FIG. 22B), lobed (as shown in FIGS. 28B, 29B, and 31), square, rectangular, or any shape desired.

28A-31, a funnel-shaped support 5300 is shown having at least one sidewall 5302 with multiple leaf-shaped longitudinal folds 5304 along the length L7 of the sidewall 5302. An outer periphery 1002 or protected surface area 1001 comprises the outer surface or outer wall 5032 of the funnel-shaped support 5300. One or more drain holes, ports, or perforations, or internal openings are disposed on the protected or inner surface area 1000 of the funnel-shaped support 5300. As shown in FIG. 28B, there is a single drain hole at the base portion of the funnel-shaped support, although multiple holes may be present.

The number of folds 5304 can range from 2 to about 20 or about 6, as shown. In this example, the folds 5304 can be formed from one or more flexible materials, such as silicone, polymer, solid material, fabric, or permeable mesh, to provide the desired leaf-like shape. The folds 5304 can have a generally rounded shape, as shown in cross-sectional view 51B. The depth D100 of each fold 5304 at the distal end 5306 of the funnel-shaped support 5300 can be the same or vary and can range from about 0.5 mm to about 5 mm.

29A and 29B, the one or more folds 5304 can include at least one longitudinal support member 5308. The longitudinal support member 5308 can span the entire length L7 or a portion of the length L7 of the funnel-shaped support 5300. The longitudinal support member 5308 can be formed from a flexible but partially rigid material such as a temperature sensitive shape memory material, e.g., Nitinol. The thickness of the longitudinal support member 5308 can range from about 0.01 mm to about 1 mm, as desired. In some embodiments, the Nitinol frame can be coated with a suitable waterproof material, such as silicone, to form a tapered portion or funnel. Fluid is then allowed to flow down the inner surface 5310 of the funnel-shaped support 5300 and into the drain lumen 5312. In other embodiments, the folds 5304 are formed from various rigid or partially rigid sheets or materials that are bent or molded to form a funnel-shaped retention portion.

30 and 31, the distal end or edge 5400 of the fold 5402 can include at least one edge support member 5404. The edge support member 5404 can span the entire circumference 5406 of the distal edge 5400 of the funnel-shaped support 5408 or one or more portions of the circumference 5406. The edge support member 5404 can be formed from a flexible but partially rigid material such as a temperature sensitive shape memory material, e.g., Nitinol. The thickness of the edge support member 5404 can range from about 0.01 mm to about 1 mm, as desired.

18A-C, the distal end 5010 of the drainage lumen 5002 (or funnel-shaped support 5014) can have an inwardly facing edge 5026 oriented toward the center of the funnel-shaped support 5014, for example, about 0.01 mm to about 1 mm, to inhibit inflammation of the kidney tissue. Thus, the funnel-shaped support 5014 can have a third diameter D7 that is less than the second diameter D5, the third diameter D7 being closer to the end 5010 of the distal portion 5004 of the drainage lumen 5002 than the second diameter D5. The outer surface 5028 of the edge 5026 can be rounded, square-edged, or any shape desired. The edge 5026 can help provide additional support to the renal pelvis and internal kidney tissue.

24A-C, in some embodiments, the edge 5200 of the distal end 5202 of at least one sidewall 5204 can be shaped. For example, the edge 5200 can comprise a plurality of generally rounded edges 5206 or scallops, e.g., from about 4 to about 20 or more rounded edges. The rounded edges 5206 provide a greater surface area than straight edges and can help support the renal pelvis or kidney tissue and prevent blockage. The edge 5200 can have any shape desired, but is preferably essentially free or devoid of sharp edges to avoid damaging tissue.

18A-C and 22A-23B, the funnel-shaped support 5014 includes a base portion 5024 adjacent the distal portion 5004 of the exhaust lumen 5002. The base portion 5024 includes at least one internal opening 5030 aligned with the internal lumen 5032 of the proximal portion 5006 of the exhaust lumen 5002 to allow fluid flow into the internal lumen 5032 of the proximal portion 5006 of the exhaust lumen 5002. In some embodiments, the cross-section of the opening 5030 is circular, although the shape may vary, such as oval, triangular, square, etc.

In some embodiments, such as those shown in FIGS. 22A-23B, the central axis 5018 of the funnel-shaped support 5014 is offset relative to the central axis 5034 of the proximal portion 5006 of the exhaust lumen 5002. The offset distance X from the central axis 5018 of the funnel-shaped support 5014 relative to the central axis 5034 of the proximal portion 5006 can range from about 0.1 mm to about 5 mm.

At least one internal opening 5030 of the base portion 5024 has a diameter D8 ranging from about 0.05 mm to about 4 mm (e.g., as shown in FIGS. 18C and 23B). In some embodiments, the diameter D8 of the internal opening 5030 of the base portion 5024 is approximately equal to the first inner diameter D6 of the adjacent proximal portion 5006 of the exhaust lumen.

In some embodiments, the ratio of the height H5 of the at least one sidewall 5016 of the funnel-shaped support 5014 to the second outer diameter D5 of the at least one sidewall 5016 of the funnel-shaped support 5014 ranges from about 1:25 to about 5:1.

In some embodiments, at least one internal opening 5030 of the base portion 5024 has a diameter D8 ranging from about 0.05 mm to about 4 mm, the height H5 of at least one sidewall 5016 of the funnel-shaped support 5014 ranges from about 1 mm to about 25 mm, and the second outer diameter D5 of the funnel-shaped support 5014 ranges from about 5 mm to about 25 mm.

In some embodiments, the thickness T1 (e.g., as shown in FIG. 18B) of at least one sidewall 5016 of the funnel-shaped support 5014 can range from about 0.01 mm to about 1.9 mm or from about 0.5 mm to about 1 mm. The thickness T1 can be generally uniform throughout the at least one sidewall 5016, or can vary as desired. For example, the thickness T1 of the at least one sidewall 5016 can be thinner or thicker near the distal end 5010 of the distal portion 5004 of the exhaust lumen 5002 than at the base portion 5024 of the funnel-shaped support 5014.

18A-21, along the length of at least one sidewall 5016, the sidewall 5016 can be straight (as shown in FIGS. 18A and 20), convex (as shown in FIG. 19), concave (as shown in FIG. 21), or any combination thereof. As shown in FIGS. 19 and 21, the curvature of the sidewall 5016 can be approximated from a radius of curvature R from point Q such that a circular shape centered at Q meets the curve and has the same slope and curvature as the curve. In some embodiments, the radius of curvature ranges from about 2 mm to about 12 mm. In some embodiments, the funnel-shaped support 5014 has a generally hemispherical shape, as shown in FIG. 19.

In some embodiments, at least one sidewall 5016 of the funnel-shaped support 5014 is formed from a balloon 5100, for example, as shown in FIGS. 35A, 35B, 38A, and 38B. The balloon 5100 can have any shape that provides funnel-shaped support and prevents obstruction of the ureter, renal pelvis, and/or remnants of the kidney. As shown in FIGS. 35A and 35B, the balloon 5100 has a funnel shape. The balloon can be inflated after insertion or deflated before removal by adding or removing gas or air through the gas port 5102. The gas port 5102 can simply be continuous with the interior 5104 of the balloon 5100, for example, the balloon 5100 can surround the exterior 5108 adjacent the interior 5106 or adjacent portions of the proximal portion 5006 of the drainage lumen 5002. The diameter D9 of the sidewall 5110 of the balloon 5100 can range from about 1 mm to about 3 mm and can vary along its length such that the sidewall has a uniform diameter, tapers toward the distal end 5112 of the funnel-shaped support 5116, or tapers toward the proximal end 5114. The outer diameter D10 of the distal end 5112 of the funnel-shaped support 5116 can range from about 5 mm to about 25 mm.

In some embodiments, at least one sidewall 5016 of the funnel-shaped support 5014 is continuous along a height H5 of the at least one sidewall 5016, for example, as shown in Figures 18A, 19, 20, and 21. In some embodiments, at least one sidewall 5016 of the funnel-shaped support 5014 comprises a solid wall, for example, the sidewall 5016 is impermeable through the sidewall after 24 hours of contact with a fluid, such as urine, on one side.

In some embodiments, at least one sidewall of the funnel-shaped support is interrupted along the height or body of the at least one sidewall. As used herein, "intermittent" means that at least one sidewall comprises at least one opening for permitting the flow of fluid or urine therethrough into the drainage lumen, e.g., by gravity or negative pressure. In some embodiments, the opening can be a conventional opening through the sidewall, or an opening in a mesh material, or an opening in a permeable fabric. The cross-sectional shape of the opening can be circular or non-circular, such as rectangular, square, triangular, polygonal, elliptical, etc., as desired. In some embodiments, the "opening" is a gap between adjacent coils in a retention portion of a catheter that comprises a coiled tube or conduit.

As used herein, an "opening" or "hole" refers to a continuous void space or channel through a sidewall from the outside to the inside of the sidewall or vice versa. In some examples, each of the at least one opening can have an area, which can be the same or different, and can range from about 0.002 mm ² to about 100 mm ² or from about 0.002 mm ² to about 10 mm ^2. As used herein, the "area" or "surface area" or "cross-sectional area" of an opening refers to the minimum or smallest planar area defined by the perimeter of the opening. For example, if an opening is circular and has a diameter of about 0.36 mm (area of 0.1 mm ² ) on the outside of the sidewall, but only a diameter of 0.05 mm (area of 0.002 mm ² ) at some point within the sidewall or on the opposite side of the sidewall, then the "area" would be 0.002 mm ² , since this is the minimum or smallest planar area for flow through the opening in the sidewall. If the opening is a square or rectangle, the "area" would be the length times the width of the planar area. For any other shape, the "area" can be determined by conventional mathematical calculations well known to those skilled in the art. For example, the "area" of an irregularly shaped opening is found by fitting shapes to fill the planar area of the opening, calculating the area of each shape, and adding the areas of each shape together.

In some embodiments, at least a portion of the sidewall comprises at least one opening. Generally, the central axis of the opening can be approximately perpendicular to the planar outer surface of the sidewall, or the opening can be angled relative to the planar outer surface of the sidewall. The bore dimensions of the opening can be uniform throughout its depth, or the width can vary along the depth by either increasing, decreasing, or alternating in width through the opening from the exterior surface of the sidewall to the interior surface of the sidewall.

9A-9E, 10A, 10E, 11-14, 27, 32A, 32B, 33, and 34, in some embodiments, at least a portion of the sidewall comprises at least one opening (one or more). The openings can be positioned anywhere along the sidewall. For example, the openings can be positioned uniformly throughout the entire sidewall, or within a defined region of the sidewall, such as closer to the distal end of the sidewall, or closer to the proximal end of the sidewall, or vertically or horizontally or in random groups along the length or circumference of the sidewall. Without intending to be bound by any theory, it is believed that openings in the proximal portion of the funnel-shaped support directly adjacent to the ureter, renal pelvis, and/or other renal tissues when negative pressure is applied to the proximal end of the proximal portion of the drainage lumen may be undesirable because such openings would reduce the negative pressure at the distal portion of the ureteral catheter, thereby reducing the withdrawal or flow of fluid or urine from the kidney and renal pelvis, possibly causing tissue irritation.

The number of openings can vary from 1 to 1000 or more, as desired. For example, in Figure 27, six openings (three on each side) are shown. As discussed above, in some embodiments, each of the at least one opening can have an area that can be the same or different and can range from about 0.002 ^mm2 to about 50 ^mm2 or from about 0.002 ^mm2 to about ¹⁰ mm2.

27, the openings 5500 can be positioned closer to the distal end 5502 of the sidewall 5504. In some embodiments, the openings are positioned in the distal half 5506 of the sidewall toward the distal end 5502. In some embodiments, the openings 5500 are evenly distributed around the circumference of the distal half 5506 or even closer to the distal end 5502 of the sidewall 5504.

In contrast, in FIG. 32B, the opening 5600 is positioned near the proximal end 5602 of the inner sidewall 5604 and does not directly contact the tissue because the outer sidewall 5606 is between the opening 5600 and the tissue. Alternatively, or in addition, one or more openings 5600 can be positioned near the distal end of the inner sidewall, as desired. The inner sidewall 5604 and the outer sidewall 5606 can be connected by one or more supports 5608 or ridges that connect the outer side 5610 of the inner sidewall 5604 to the inner side 5612 of the outer sidewall 5606.

In some non-limiting examples, such as those shown in Figures 9A-9E, 10A, 10D-10G, 18B, 18D, 18E, 20, 22A, 22B, 23A, 23B, 24A-24C, 25, 26, 27, 28A, 28B, 29A-29C, 30, 31, 32A, 32B, 33, 34, 35A, 35B, 37B, 38A, 39B, 39C, 40A-40C, and 41A-41C, the protected surface area or inner surface area 1000 can be established by a variety of different shapes or materials. Non-limiting examples of protected surface areas or inner surface areas 1000 include, for example, the inner portions 152, 5028, 5118, 5310, 5410, 5510, 5616, 5710, 5814, 6004 of the funnels 150, 5014, 5116, 5300, 5408, 5508, 5614, 5702, 5802, 6000, the coils 183, 184, 185, 187, 334, 1280, 1282, 1284, inner portions 164, 166, 168, 170, 338, 1281, 1283, 1285, inner portions 5902, 6003 of porous material 5900, 6002, inner portions 162, 5710, 5814 of mesh 57, 5704, 5804, or inner portion 536 of cage 530 with protected drainage hole 533.

In some non-limiting examples, one or more protected drain holes, ports, or perforations 133, 1233 are disposed on the protected surface area 1000. In response to application of negative pressure therapy through the catheter, the urothelial or mucosal tissue 1003, 1004 conforms or collapses onto the outer periphery 189, 1002 or protected surface area 1001 of the retention portion 130, 330, 410, 500, 1230, 1330, 2230, 3230, 4230, 5012, 5013 of the catheter, thereby preventing or inhibiting occlusion of one or more of the protected drainage holes, ports, or perforations 133, 1233 located on the protected or inner surface area 1000, thereby establishing, maintaining, or enhancing a patent fluid column or flow between the renal pelvis and calyx and the drainage lumen 124, 324, 424, 524, 1224, 5002, 5003, 5312, 5708, 5808.

In some embodiments, the retention portion 130, 330, 410, 500, 1230, 1330, 2230, 3230, 4230, 5012, 5013 comprises one or more helical coils having an outwardly facing side 1288 and an inwardly facing side 1286, the outer periphery 1002 or protected surface area 1001 comprises the outwardly facing side 1288 of the one or more helical coils, and one or more protected vent holes, ports, or perforations 133, 1233 are disposed on the inwardly facing side 1286 (protected surface area or inner surface area 1000) of the one or more helical coils.

For example, a funnel shape as shown in Fig. 25 can create a sidewall 5700 that conforms to the natural anatomical shape of the renal pelvis and prevents the urothelium from constricting the fluid column. The interior 5710 of the funnel-shaped support 5702 provides a protected surface area 1000 having openings 5706 therethrough that provide a passageway through which the fluid column may flow from the calyx into the drainage lumen 5708. Similarly, the mesh configuration of Fig. 26 can also create a protected surface area 1000, such as the interior 5814 of the mesh 5804, between the calyx and the drainage lumen 5808 of the catheter. The mesh 5704, 5804 includes multiple openings 5706, 5806 therethrough to allow fluid flow into the drainage lumen 5708, 5808. In some examples, the maximum area of the openings can be less than about 100 mm ² , or less than about 1 mm ² , or from about 0.002 mm ² to about 1 mm ² , or from about 0.002 mm ² to about 0.05 mm ^2. The mesh 5704, 5804 can be formed from any suitable metallic or polymeric material as discussed above.

In some embodiments, the funnel-shaped support further comprises a cover portion over the distal end of the funnel-shaped support. The cover portion can be formed as an integral part of the funnel-shaped support or can be connected to the distal end of the funnel-shaped support. For example, as shown in FIG. 26, the funnel-shaped support 5802 comprises a cover portion 5810 that traverses and protrudes from the distal end 5812 of the funnel-shaped support 5802. The cover portion 5810 can have any desired shape, such as flat, convex, concave, wavy, and combinations thereof. The cover portion 5810 can be formed from a mesh or any polymeric solid material, as discussed above. The cover portion 5810 can provide an outer perimeter 1002 or protective surface area 1001 to support soft tissue in the kidney area and help promote urine production.

In some embodiments, the funnel-shaped support comprises a porous material, as shown, for example, in Figures 39A-40C. Figures 39A-40C and suitable porous materials are discussed in detail below. Briefly, in Figures 39 and 40, the porous material itself is the funnel-shaped support. In Figure 39, the funnel-shaped support is a wedge of porous material. In Figure 40, the porous material is in the shape of a funnel. In some embodiments, such as Figure 33, the porous material 5900 is positioned within an interior 5902 of a sidewall 5904. In some embodiments, such as Figure 34, the funnel-shaped support 6000 comprises a porous liner 6002 positioned adjacent an interior 6004 of a sidewall 6006. The thickness T2 of the porous liner 6002 can range, for example, from about 0.5 mm to about 12.5 mm. The area of the openings in the porous material can be from about 0.002 mm ² to about 100 mm ² or less.

37A and 37B, for example, the retention portion 130 of the ureteral catheter 112 comprises, in some embodiments, a catheter tube 122 having a flared and/or tapered distal end portion configured to be positioned within the renal pelvis and/or kidney of a patient. For example, the retention portion 130 can be a funnel-shaped structure having an outer surface 185 configured to be positioned against the ureter and/or kidney wall and an inner surface 186 configured to direct fluid toward the drainage lumen 124 of the catheter 112. The retention portion can be configured into a funnel-shaped support having an outer surface 185 and an inner surface 186, where an outer perimeter 189 or protective surface area 1001 comprises the outer surface 185 of the funnel-shaped support and one or more drainage holes, ports, or perforations 133, 1233 are disposed on the inner surface 186 at the base of the funnel-shaped support. In another embodiment shown in FIGS. 32A and 32B, the retention portion can be configured as a funnel-shaped support 5614 having an outer surface 185 and an inner surface 5616, and the outer perimeter 1002 or protected surface area 1001 can comprise the outer surface of the outer sidewall 5606. The protected surface area 1000 can comprise the inner sidewall 5604 of the inner funnel, and one or more drain holes, ports, or perforations 5600 can be disposed on the inner sidewall 5604 of the funnel-shaped support.

37A and 37B, the retention portion 130 can include a proximal end 188 adjacent the distal end of the drainage lumen 124 and having a first diameter D1, and a distal end 190 having a second diameter D2 that is greater than the first diameter D1 when the retention portion 130 is in its deployed position. In some embodiments, the retention portion 130 can be transitioned from a collapsed or compressed position to a deployed position. For example, the retention portion 130 can be biased radially outward such that when the retention portion 130 is advanced to its fluid collection position, the retention portion 130 (e.g., a funnel portion) expands radially outward to the deployed state.

The retention portion 130 of the ureteral catheter 112 can be made from a variety of suitable materials capable of transitioning from a collapsed state to an expanded state. In one embodiment, the retention portion 130 comprises a framework of tines or elongated members formed from a temperature sensitive shape memory material such as Nitinol. In some embodiments, the Nitinol frame can be coated with a suitable waterproof material such as silicone to form a tapered portion or funnel. Fluid is then allowed to flow down the inner surface 186 of the retention portion 130 into the drainage lumen 124. In other embodiments, the retention portion 130 is formed from a variety of rigid or partially rigid sheets or materials that are bent or molded to form a funnel-shaped retention portion, as illustrated in FIGS. 37A and 37B.

In some examples, the retention portion of the ureteral catheter 112 can include one or more mechanical stimulation devices 191 for providing stimulation to nerve and muscle fibers in the adjacent tissue of the ureter and renal pelvis. For example, the mechanical stimulation device 191 can include a linear or annular actuator embedded in or mounted adjacent to a portion of the sidewall of the catheter tube 122 and configured to emit low-level vibrations. In some examples, mechanical stimulation can be provided to a portion of the ureter and/or renal pelvis to complement or modify the therapeutic effect obtained by the application of negative pressure. Without intending to be bound by theory, such stimulation is believed to affect adjacent tissues, for example, by stimulating nerves associated with the ureter and/or renal pelvis and/or by activating peristaltic muscles. Stimulation of nerves and activation of muscles can result in changes in pressure gradients or pressure levels within the surrounding tissues and organs, which can contribute to or in some cases enhance the therapeutic benefits of negative pressure therapy.

38A and 38B, according to another embodiment, the retention portion 330 of the ureteral catheter 312 comprises a catheter tube 322 having a distal portion 318 formed into a helical structure 332 and an expandable element or balloon 350 positioned proximal to the helical structure 332 to provide additional retention in the renal pelvis and/or fluid collection site. The balloon 350 can be inflated to a pressure sufficient to retain the balloon in the renal pelvis or ureter, but low enough to avoid distending or damaging these structures. Suitable inflation pressures are known to those skilled in the art and can be readily determined by trial and error. As in the previous embodiment, the helical structure 332 can be imparted by bending the catheter tube 322 to form one or more coils 334. The coils 334 can have a constant or variable diameter and height, as described above. The catheter tube 322 further includes a number of drainage ports 336 disposed on the sidewall of the catheter tube 322 that allow urine to be drawn into the drainage lumen 324 of the catheter tube 322 and directed from the body, for example, through the drainage lumen 324 on the inward-facing and/or outward-facing sides of the coil 334.

As shown in FIG. 38B, the expandable element or balloon 350 can comprise, for example, an annular balloon-like structure having a generally heart-shaped cross-section and a surface or cover 352 defining a cavity 353. The cavity 353 is in fluid communication with an inflation lumen 354 extending parallel to the drainage lumen 324 defined by the catheter tube 322. The balloon 350 can be configured to be inserted into the tapered portion of the renal pelvis and inflated such that its outer surface 356 contacts and rests against the inner surface of the ureter and/or renal pelvis. The expandable element or balloon 350 can comprise a tapered inner surface 358 extending longitudinally and radially inwardly toward the catheter tube 322. The inner surface 358 can be configured to direct urine to be drawn toward the catheter tube 322 into the drainage lumen 324. The inner surface 358 can also be positioned to prevent fluid from pooling within the ureter, such as around the periphery of the expandable element or balloon 350. The expandable retention portion or balloon 350 is desirably sized to fit within the renal pelvis and can have a diameter ranging from about 10 mm to about 30 mm.

39A-40C, an assembly 400 is illustrated that, in some embodiments, includes a ureteral catheter 412 with a retention portion 410. The retention portion 410 is formed of a porous and/or sponge-like material attached to the distal end 421 of a catheter tube 422. The porous material can be configured to carry and/or absorb urine and direct the urine toward the drainage lumen 424 of the catheter tube 422. The retention portion 410 can be configured into a funnel-shaped support having an outer surface and an inner surface, where the outer perimeter 1002 or protective surface area 1001 comprises the outer surface of the funnel-shaped support, and one or more drainage holes, ports, or perforations in the porous material can be disposed within the porous material or on the inner surface 426 of the funnel-shaped support.

As shown in FIG. 40, the retention portion 410 can be a porous wedge-shaped structure configured for insertion and retention within the renal pelvis of a patient. The porous material includes a plurality of pores and/or channels. Fluid can be drawn through the channels and pores, for example, by gravity or in response to the induction of negative pressure through the catheter 412. For example, fluid can enter the wedge-shaped retention portion 410 through the pores and/or channels and be drawn toward the distal opening 420 of the drainage lumen 424, for example, by capillary action, peristalsis, or as a result of the induction of negative pressure within the pores and/or channels. In another example, as shown in FIG. 40, the retention portion 410 comprises a hollow funnel structure formed from a porous sponge-like material. As shown by arrow A, fluid is directed along the inner surface 426 of the funnel structure into the drainage lumen 424 defined by the catheter tube 422. Fluid can also enter the funnel structure of the retention portion 410 through holes and channels in the porous sponge-like material of the sidewall 428. For example, a suitable porous material can include an open-cell polyurethane foam, such as polyurethane ether. Suitable porous materials can also include a laminate of layers of woven or non-woven fabrics, including, for example, polyurethane, silicone, polyvinyl alcohol, cotton, or polyester, with or without antimicrobial additives, such as silver, and with or without additives to modify the material properties, such as hydrogels, hydrocolloids, acrylics, or silicones.

41, according to another embodiment, the retention portion 500 of the ureteral catheter 512 comprises an expandable cage 530. The expandable cage 530 comprises one or more longitudinally and radially extending hollow tubes 522. For example, the tubes 522 can be formed from an elastic shape memory material such as Nitinol. The cage 530 is configured to transition from a contracted state for insertion through the patient's urinary tract to an expanded state for positioning within the patient's ureter and/or kidney. The hollow tubes 522 comprise a number of drainage ports 534 that may be positioned on the tubes, e.g., on their radially inward facing sides. The ports 534 are configured to allow fluid to flow or be withdrawn through the ports 534 into the individual tubes 522. The fluid is drained through the hollow tubes 522 into a drainage lumen 524 defined by the catheter body 526 of the ureteral catheter 512. For example, the fluid can flow along a path indicated by the arrows 532 in FIG. In some examples, when negative pressure is induced within the renal pelvis, kidney, and/or ureter, a portion of the ureteral wall and/or renal pelvis may be retracted against the outwardly facing surface of the hollow tube 522. The exit port 534 is positioned and configured such that it is not significantly obstructed by the ureteral structures in response to the application of negative pressure to the ureter and/or kidney.

In some embodiments, a ureteral catheter comprising a funnel-shaped support can be deployed into the patient's urinary tract, more specifically into the renal pelvis region/kidney, using a conduit through the urethra into the bladder. The funnel-shaped support 6100 is in a collapsed state (shown in FIG. 36 ) and is housed within a ureteral sheath 6102. To deploy a ureteral catheter, a medical professional will insert a cystoscope into the urethra to provide a channel for tools to enter the bladder. The ureteral orifice will be visualized and a guidewire will be inserted through the cystoscope and ureter until the tip of the guidewire reaches the renal pelvis. The cystoscope will possibly be removed and a "pusher tube" will be passed over the guidewire to the renal pelvis. The guidewire will be removed while the "pusher tube" remains in place and acts as a deployment sheath. The ureteral catheter will be inserted through the pusher tube/sheath and the catheter tip will be actuated once it extends beyond the end of the pusher tube/sheath. The funnel-shaped support will expand radially and assume a deployed position.
Exemplary ureteral stents:

1A, in some embodiments, the ureteral stent 52, 54 comprises an elongate body having a proximal end 62, a distal end 58, a longitudinal axis, and at least one drainage channel extending along the longitudinal axis from the proximal end to the distal end to maintain patency of fluid flow between the kidney and the bladder of the patient. In some embodiments, the ureteral stent further comprises a pigtail coil or loop on at least one of the proximal or distal ends. In some embodiments, the body of the ureteral stent further comprises at least one perforation on its sidewall. In other embodiments, the body of the ureteral stent is essentially free or free of perforations on its sidewall.

Some examples of ureteral stents 52, 54 that may be useful in the present systems and methods include the CONTOUR ^™ ureteral stent, CONTOUR VL ^™ ureteral stent, POLARIS ^™ Loop ureteral stent, POLARIS ^™ Ultra ureteral stent, PERCUFLEX ^™ ureteral stent, PERCUFLEX ^™ Plus ureteral stent, and STRETCH ^™ VL Flexima ureteral stent, each of which are commercially available from Boston Scientific Corporation, Natick, Massachusetts. See "Ureteral Stent Portfolio," a Boston Scientific Corp. publication (July 2010), which is incorporated herein by reference. CONTOUR ^TM and CONTOUR VL ^TM ureteral stents are constructed of soft Percuflex ^TM material that softens at body temperature and is designed for a 365 day placement time. Variable length coils on the distal and proximal ends allow one stent to fit a variety of ureteral lengths. Fixed length stents can be 6F-8F with lengths ranging from 20cm-30cm, and variable length stents can be 4.8F-7F with lengths ranging from 22-30cm. Other examples of suitable ureteral stents include the INLAY® ureteral stent, INLAY® OPTIMA® ureteral stent, BARDEX® double pigtail ureteral stent, and FLUORO-4 ^TM silicone ureteral stent, each commercially available from C. R. Bard, Inc. (Murray Hill, NJ). See "Uretral Stents", http://www.bardmedical.com/products/kidney-stone-management/ureteral-stents/ (January 21, 2018) (incorporated herein by reference).

The stents 52, 54 can be deployed in one or both kidneys or renal areas (renal pelvis or ureter adjacent to the renal pelvis) of a patient as desired. Typically, these stents are deployed by inserting the stent with the Nitinol wire through it through the urethra and bladder to the kidney, then removing the Nitinol wire from the stent and allowing the stent to assume a deployed configuration. Many of the above stents have flat loops 58, 60 on the distal end (to be deployed in the kidney), and some also have flat loops 62, 64 on the proximal end of the stent, which are deployed in the bladder. When the Nitinol wire is removed, the stent assumes a pre-stressed flat loop shape at the distal and/or proximal ends. To remove the stent, a Nitinol wire is inserted to straighten the stent, and the stent is removed from the ureter and urethra.

Other examples of suitable ureteral stents 52, 54 are disclosed in PCT Patent Application Publication No. WO2017/019974, which is incorporated herein by reference. In some examples, as shown, for example, in Figures 1-7 of WO2017/019974 and Figure 3 herein (which is identical to Figure 1 of WO2017/019974), a ureteral stent 100 can comprise an elongate body 101 having a proximal end 102, a distal end 104, a longitudinal axis 106, an outer surface 108, and an inner surface 110 that defines a deformable bore 111 extending along the longitudinal axis 106 from the proximal end 102 to the distal end 104, and at least two fins 112 projecting radially away from the outer surface 108 of the body 101, the deformable bore 111 being formed by the elongate body 101. The deformable bore 111 has (a) a default orientation 113A (shown on the left in FIG. 59) with an open bore 114 defining a longitudinally open channel 116, and (b) a second orientation 113B (shown on the right in FIG. 59) with an at least essentially closed bore 118 or closed bore defining a longitudinally essentially closed exhaust channel 120 along the longitudinal axis 106 of the elongated body 101, and the deformable bore 111 is movable from the default orientation 113A to the second orientation 113B in response to a radial compressive force 122 applied to at least a portion of the outer surface 108 of the body 101.

3, the drainage channel 120 of the ureteral stent 100 has a diameter D that is reduced in response to the deformable bore 111 moving from the default orientation 113A to the second orientation 113B, and the diameter can be reduced to a point above which urine flow through the deformable bore 111 would be reduced. In some embodiments, the diameter D is reduced by up to about 40% in response to the deformable bore 111 moving from the default orientation 113A to the second orientation 113B. In some embodiments, the diameter D in the default orientation 113A can range from about 0.75 to about 5.5 mm, or about 1.3 mm, or about 1.4 mm. In some embodiments, the diameter D in the second orientation 113B can range from about 0.4 to about 4 mm, or about 0.9 mm.

In some embodiments, the one or more fins 112 comprise a flexible material that is soft to medium soft based on the Shore hardness scale. In some embodiments, the body 101 comprises a flexible material that is medium hard to hard based on the Shore hardness scale. In some embodiments, the one or more fins have a hardness of about 15A to about 40A. In some embodiments, the body 101 has a hardness of about 80A to about 90A. In some embodiments, the one or more fins 112 and the body 101 comprise a flexible material that is medium soft to medium hard based on the Shore hardness scale, for example, having a hardness of about 40A to about 70A.

In some embodiments, one or more fins 112 and body 101 comprise a flexible material that is medium to hard based on the Shore hardness scale, e.g., having a hardness of about 85A to about 90A.

In some embodiments, the default orientation 113A and the second orientation 113B support fluid or urine flow through the deformable bore 111 as well as around the outer surface 108 of the stent 100.

In some embodiments, one or more fins 112 extend longitudinally from the proximal end 102 to the distal end 104. In some embodiments, the stent has two, three, or four fins.

In some embodiments, the body outer surface 108 has an outer diameter in the default orientation 113A ranging from about 0.8 mm to about 6 mm or about 3 mm. In some embodiments, the body outer surface 108 has an outer diameter in the second orientation 113B ranging from about 0.5 mm to about 4.5 mm or about 1 mm. In some embodiments, the one or more fins have a width or tip ranging from about 0.25 mm to about 1.5 mm or about 1 mm and protrude from the body outer surface 108 in a direction generally perpendicular to the longitudinal axis.

In some embodiments, the radial compressive force is provided by at least one of normal ureteral physiology, abnormal ureteral physiology, or the application of any external force. In some embodiments, the ureteral stent 100 is purposefully adapted to a dynamic ureteral environment, the ureteral stent 100 comprising an elongate body 101 having a proximal end 102, a distal end 104, a longitudinal axis 106, an outer surface 108, and an inner surface 110 defining a deformable bore 111 extending along the longitudinal axis 106 from the proximal end 102 to the distal end 104, the deformable bore 111 having (a) a default orientation 113A with an open bore 114 defining a longitudinally open channel 116, and (b) a default orientation 113B with an open bore 114 defining a longitudinally open channel 116, and (c) a default orientation 113C with an open bore 114 defining a longitudinally essentially closed channel 120. and a second orientation 113B having an at least essentially closed bore 118 that is in a radially compressive state, the deformable bore being movable from a default orientation 113A to the second orientation 113B in response to a radial compressive force 122 being applied to at least a portion of the outer surface 108 of the body 101, the inner surface 110 of the body 101 having a diameter D that is reduced in response to the deformable bore 111 moving from the default orientation 113A to the second orientation 113B, the diameter being reduceable to a point above which fluid flow through the deformable bore 111 would be reduced. In some examples, the diameter D is reduced by up to about 40% in response to the deformable bore 111 moving from the default orientation 113A to the second orientation 113B.

Other examples of suitable ureteral stents are disclosed in U.S. Patent Application Publication No. US 2002/0183853 A1, which is incorporated herein by reference. In some embodiments, as shown, for example, in Figures 4, 5, and 7 of US 2002/0183853 A1 and Figures 4-6 herein (which are identical to Figures 1, 4, 5, and 7 of US 2002/0183853 A1), the ureteral stent comprises an elongate body 10 having a proximal end 12, a distal end 14 (not shown), a longitudinal axis 15, and at least one drainage channel (e.g., 26, 28, 30 in FIG. 4; 32, 34, 36, and 38 in FIG. 5; 48 in FIG. 6) that extends along the longitudinal axis 15 from the proximal end 12 to the distal end 14 and maintains patency for fluid flow between the kidney and the bladder of a patient. In some embodiments, the at least one drainage channel is partially open along at least a longitudinal portion thereof. In some embodiments, the at least one drainage channel is closed along at least a longitudinal portion thereof. In some embodiments, the at least one drainage channel is closed along its longitudinal length. In some embodiments, the ureteral stent is radially compressible. In some embodiments, the ureteral stent is radially compressible, narrowing the at least one drainage channel. In some embodiments, the elongate body 10 comprises at least one external fin 40 along the longitudinal axis 15 of the elongate body 10. In some embodiments, the elongate body comprises 1-4 drainage channels. The diameter of the drainage channel can be the same as described above.
System for inducing negative pressure

In some embodiments, a system for inducing negative pressure within a portion of a patient's urinary tract or removing fluid from the patient's urinary tract is provided, comprising a ureteral stent or ureteral catheter for maintaining patency of fluid flow between at least one of the patient's kidneys and the bladder, a bladder catheter having a drainage lumen for draining fluid from the patient's bladder, and a pump in fluid communication with a distal end of the drainage lumen, the pump comprising a controller configured to actuate the pump to apply negative pressure to a proximal end of the catheter to induce negative pressure within a portion of the patient's urinary tract and remove fluid from the patient's urinary tract.

In some embodiments, a system for inducing negative pressure within a portion of a patient's urinary tract is provided, the system comprising: (a) a ureteral catheter having a distal portion for insertion within the patient's kidney and a proximal portion; (b) a bladder catheter having a distal portion for insertion within the patient's bladder and a proximal portion for application of negative pressure, the proximal portion extending outside the patient's body; and (c) a pump that is external to the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, thus drawing fluid from the kidney into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body.

In some embodiments, a system for inducing negative pressure within a portion of a patient's urinary tract is provided, the system comprising: (a) at least one ureteral catheter having a distal portion for insertion within the patient's kidney and a proximal portion; and (b) a bladder catheter having a distal portion for insertion within the patient's bladder and a proximal portion for receiving negative pressure from a negative pressure source, wherein at least one of the at least one ureteral catheter or bladder catheter has (a) a proximal portion and (b) a distal portion having one or more protected drain holes, (c) a bladder catheter having a distal portion with a retention portion configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from blocking one or more protected drains, ports, or perforations in response to application of negative pressure through the catheter; and (b) a negative pressure source for application of negative pressure through both the bladder catheter and the ureteral catheter, thereby drawing fluid from the kidney into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body.

In some embodiments, a system for inducing negative pressure within a portion of a patient's urinary tract comprises: (a) at least one ureteral catheter, the at least one ureteral catheter comprising a distal portion for insertion within the patient's kidney and a proximal portion; and (b) a bladder catheter comprising a distal portion for insertion within the patient's bladder and a proximal portion for receiving a pressure differential, the pressure differential being applied to draw fluid from the kidney into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body, the pressure differential being applied to increase, decrease, and/or maintain fluid flow therethrough, at least one of the at least one ureteral or bladder catheter comprising: (a) a proximal portion; and (b) a distal portion comprising one or more protected drains, ports, or perforations, the distal portion comprising a retaining portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drains, ports, or perforations in response to application of a pressure differential through the catheter.

1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, an exemplary system 1100 for inducing negative pressure in a patient's urinary tract to increase renal perfusion is illustrated. The system 1100 comprises one or two ureteral catheters 1212 (or alternatively, a ureteral stent as shown in FIG. 1A) connected to a fluid pump 2000 to generate negative pressure. More specifically, the patient's urinary tract comprises the patient's right kidney 2 and left kidney 4. The kidneys 2, 4 are responsible for blood filtration and clearance of waste compounds from the body through urine. Urine or fluid produced by the right kidney 2 and left kidney 4 is drained into the patient's bladder 10 through renal tubules, i.e., the right ureter 6 and left ureter 8, which are connected to the kidneys at the renal pelvis 20, 21. Urine may be conducted through the ureters 6, 8 by peristalsis of the ureteral walls as well as gravity. The ureters 6, 8 enter the bladder 10 through ureteral orifices or openings 16. The bladder 10 is a flexible and substantially hollow structure adapted to collect urine until it is discharged from the body. The bladder 10 is transitionable from an empty position (indicated by reference line E) to a full position (indicated by reference line F). Typically, when the bladder 10 reaches a substantially full state, fluid or urine is allowed to drain from the bladder 10 into the urethra 12 through a urethral sphincter or opening 18 located in the lower portion of the bladder 10. Contractions of the bladder 10 may be in response to stress and pressure exerted on the trigone region 14 of the bladder 10, which is a triangular region extending between the ureteral orifices 16 and the urethral opening 18. The trigone region 14 is sensitive to stress and pressure such that as the bladder 10 begins to fill, pressure on the trigone region 14 increases. Once a threshold pressure on the trigone region 14 is exceeded, the bladder 10 begins to contract, expelling collected urine through the urethra 12.

As shown in FIGS. 1, 2A, 7A, and 7B, the distal portion of the ureteral catheter is deployed within the renal pelvis 20, 21 near the kidneys 2, 4. The proximal portion of one or more of the catheters 1212 enters the bladder, into the urethra, or exits the body. In some embodiments, the proximal portion 1216 of the ureteral catheter 1212 is in fluid communication with the distal portion or end 136 of the bladder catheter 56, 116. The proximal portion 1216 of the bladder catheter 56, 116 is connected to a source of negative pressure, such as a fluid pump 2000. The shape and size of the connector can be selected based on the type of pump 2000 being used. In some embodiments, the connector can be manufactured with distinctly different configurations such that it can only be connected to a specific pump type, which is deemed safe for inducing negative pressure within the patient's bladder, ureter, or kidney. In other embodiments, the connector can be a more universal configuration adapted for attachment to a variety of different types of fluid pumps, as described herein. System 1100 is just one example of a negative pressure system for inducing negative pressure that may be used in conjunction with the bladder catheters disclosed herein.

1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, 7B, 17, in some embodiments, the system 50, 100 includes a bladder catheter 116. The distal ends 120, 121 of the ureteral catheters 112, 114 can drain directly into the bladder and fluid can be drained through the bladder catheter 116, optionally along the side of the bladder catheter tube.
Exemplary Bladder Catheter

Any of the ureteral catheters disclosed herein can be used as bladder catheters useful in the present methods and systems. In some embodiments, the bladder catheter 116 anchors, retains, and/or provides passive fixation for the indwelling portion of the urine collection assembly 100, and in some embodiments includes a retention portion 123 or a deployable seal and/or an anchor 136 to prevent premature and/or unintended removal of the assembly components during use. The retention portion 123 or anchor 136 is configured to be positioned adjacent the inferior wall of the patient's bladder 10 (shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, 7B, 17) and to prevent patient movement and/or forces applied to the indwelling catheters 112, 114, 116 from being transmitted to the ureter. The bladder catheter 116 includes an interior defining a drainage lumen 140 configured to conduct urine from the bladder 10 to an external urine collection container 712 (shown in FIG. 44). In some embodiments, the bladder catheter 116 tubing size can range from about 8 Fr to about 24 Fr. In some embodiments, the bladder catheter 116 can have an outer tubing diameter ranging from about 2.7 to about 8 mm. In some embodiments, the bladder catheter 116 can have an inner diameter ranging from about 2.16 to about 10 mm. The bladder catheter 116 can be available in different lengths to accommodate anatomical differences due to gender and/or patient size. For example, the average female urethral length is only a few inches, and therefore the length of the tubing 138 can be quite short. The average urethral length of a man can be longer and more variable due to the penis. It is also conceivable that a woman could use a bladder catheter 116 with a longer length of tubing 138, provided that the excess tubing does not increase the difficulty in manipulating the catheter 116 and/or preventing contamination of its sterile portion. In some embodiments, the sterile and indwelling portion of the bladder catheter 116 can range from about 1 inch to 3 inches (female) to about 20 inches (male). The total length of the bladder catheter 116, including the sterile and non-sterile portions, can be one to several feet.

In some embodiments, such as those shown in Figures 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, the distal portion 136 of the bladder catheter 56, 116 includes one or more drain holes, ports, or perforations 142 and includes a retention portion 123 configured to establish an outer perimeter 1002 or protective surface area 1001 that prevents mucosal tissue from occluding the one or more drain holes, ports, or perforations 142 in response to application of negative pressure by the pump 710, 2000.

In some embodiments where the retention portion 123 comprises a tube 138, the tube 138 may comprise one or more drain holes, ports, or perforations 142 configured to be positioned within the bladder 10 to draw urine into the drain lumen 140. For example, fluid or urine flowing from the ureteral catheters 112, 114 into the patient's bladder 10 is released from the bladder 10 through the port 142 and the drain lumen 140. The drain lumen 140 may be pressurized to a negative pressure to assist in fluid collection.

In some embodiments, such as those shown in Figures 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, one or more drainage holes, ports, or perforations 142, 172 of a bladder catheter 56, 116, such as the ureteral catheter discussed above, are positioned on the protected or inner surface area 1000 of the retention portion 123, and in response to application of negative pressure, the mucosal tissue 1003, 1004 conforms or collapses onto the outer periphery 1002 or protected surface area 1001 of the retention portion 173 of the bladder catheter 56, 116, thereby preventing or inhibiting from occluding one or more of the protected drainage holes, ports, or perforations 172 of the bladder catheter 56, 116.

1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, the retention portion 123 or deployable seal and/or anchor 136 is disposed at or adjacent to the distal end 148 of the bladder catheter 116. The retention portion 123 or deployable anchor 136 is configured to transition between a contracted state for insertion through the urethra 12 and urethral opening 18 into the bladder 10, and an deployed state. The retention portion 123 or deployable anchor 136 is configured to be deployed within a lower portion of the bladder 10 and seated adjacent thereto and/or against the urethral opening 18. For example, the retention portion 123 or deployable anchor 136 may be positioned adjacent the urethral opening 18 to enhance suction of the negative pressure applied to the bladder 10 or to partially, substantially, or completely seal the bladder 10 to ensure that urine within the bladder 10 is directed through the drainage lumen 140 and prevents leakage into the urethra 12. For a bladder catheter 116 that includes an 8Fr to 24Fr extension tube 138, the retention portion 123 or deployable anchor 136 may have a diameter of about 10 mm to about 100 mm in the deployed state.
Exemplary Bladder Anchor Structures

Any of the ureteral catheters disclosed herein can be used as a bladder catheter useful in the present methods and systems. For example, the bladder catheter can include a mesh as a bladder anchor as shown in Figures 1A, 1B, and 7B. In another example, the bladder catheter 116 can include coils 36, 38, 40, 183, 184, 185, 334, 1210 as a bladder anchor as shown in Figures 1C-1W and 7A. In another example, the bladder catheter 116 can include a mesh funnel 57 as a bladder anchor as shown in Figure 7B. In another example, the bladder catheter 116 can include a funnel 150 as a bladder anchor as shown in Figure 17. Regardless of the embodiment selected, the retention portion 123 creates an outer perimeter 1002 or protective surface area 1001 to prevent tissue 1003, 1004 from contracting or collapsing into the fluid column under negative pressure.

In some embodiments, the retention portion 123 comprises a coiled retention portion similar to the retention portion of the ureteral catheter described in connection with Figures 2A and 7A-14. In some embodiments, such as those shown in Figures 1C-1E, 1U-1W, the coiled retention portion 123 can comprise a plurality of helical coils 36, 38, 40, or 438, 436, 432 arranged such that the outer periphery 1002 or outer region of the helical coil 36, 38, 40, or 438, 436, 432 contacts and supports the bladder tissue 1004 to prevent occlusion or obstruction of a protected drain, port, or perforation 172 located within the protected or inner surface area of the helical coil 36, 38, 40, or 438, 436, 432.

The coiled retention portion 123 can include at least a first coil 36, 438 having an outer diameter D1 (see FIG. 1E), at least a second coil 38, 436 having an outer diameter D2, and at least a third coil 40, 432 having an outer diameter D3. The diameter D3 of the most distal or third coil 40, 432 can be smaller than the diameter of either the first coil 36, 438 or the second coil 38, 436. Thus, the diameter of the coils 36, 38, 40, or 438, 436, 432, and/or the step distance or height between adjacent coils 36, 38, 40, or 438, 436, 432, can vary in a regular or irregular manner. In some examples, the multiple coils 36, 38, 40, or 438, 436, 432 can form a tapered or inverted pyramidal shape, where D1>D2>D3. In some examples, the coiled retention portion 123 can comprise multiple similarly sized coils or can include, for example, multiple proximal similarly sized coils and a distal-most coil having a smaller diameter than the other coils of the multiple coils. The diameter of the coils 36, 38, 40, or 438, 436, 432 and the distance or height between adjacent coils are selected so that the retention portion 123 remains in the bladder for a desired period of time, such as hours, days, or up to about six months. The coiled retention portion 123 can be large enough to remain in the bladder 10 and not pass into the urethra until the catheter is ready to be removed from the bladder 10. For example, the outer diameter D1 of the proximal-most or first coil 36, 438 can range from about 2 mm to 80 mm. The outer diameter D2 of the second coil 38, 436 can range from about 2 mm to 60 mm. The distal-most or third coil 40, 432 can have an outer diameter D3 ranging from about 1 mm to 45 mm. The diameter of the coil tube can range from about 0.33 mm to about 9.24 mm (about 1 Fr to about 28 Fr (French catheter scale).

The configurations, sizes, and locations of the holes, ports, or perforations 142, 172 may be any of the configurations, sizes, and locations discussed above with respect to ureteral or other catheters. In some embodiments, the holes, ports, or perforations 142 are present on the outer perimeter 1002 or protected surface area 1001, and the protected holes, ports, or perforations 172 are present on the protected or inner surface area 1000. In some embodiments, the outer perimeter 1002 or protected surface area 1001 is essentially free or absent of holes, ports, or perforations 142, and the protected holes, ports, or perforations 172 are present on the protected or inner surface area 1000.

1U-1W is a coiled retention portion comprising multiple coils wrapped around a generally linear or straight portion 430 of an elongated tube 418. In some embodiments, the coiled retention portion 416 comprises a straight portion 430 and a distal-most coil 432 formed from an approximately 90-180 degree bend 434 in the elongated tube 418. The retention portion 416 further comprises one or more additional coils, such as a second or middle coil 436 and a third or proximal-most coil 438, wrapped around the straight portion 430. The elongated tube 418 can further comprise a distal end 440 after the proximal-most coil 438. The distal end 440 can be closed or can be open to receive urine or fluid from the bladder 10.

The area of a two-dimensional slice 34 (shown in FIG. 1E ) of the three-dimensional shape 32 defined by the expanded or expanded retention portion 123 in a plane transverse to the central axis A of the expandable retention portion 16 can decrease toward the distal end 22 of the expanded or expanded retention portion 123, giving the retention portion 123 a pyramidal or inverted conical shape. In some examples, the maximum cross-sectional area of the three-dimensional shape 32 defined by the expanded or expanded retention portion 123 in a plane transverse to the central axis A of the expanded or expanded retention portion 132 can range from about 100 mm ² to 1,500 mm ² , or about 750 mm ² .

Another embodiment of the catheter device 10 is shown in Figures 1F-1J. The retention portion 123 of the catheter device 10 comprises a bladder upper wall support 210 or basket-shaped structure or support cap 212 of the outer periphery 1002 configured to be disposed within the distal portion of the tube 12 in the retracted position and to extend from the distal end of the tube 12 in the deployed position. The bladder upper wall support 210 comprises a support cap 212 configured to support the upper wall or bladder tissue 1004 and a plurality of support members, such as legs 214 connected to the proximal surface of the support cap 212. The legs 214 can be positioned such that the cap 212 is spaced from the open distal end of the drain tube 12. For example, the legs 214 can be configured to maintain a gap, cavity, or space of a distance D1 between the open distal end 30 of the tube 12 and the support cap 212. The distance D1 can range from about 1 mm to about 40 mm or from about 5 mm to about 40 mm. The height D2 of the bladder upper wall support 210 or retention portion can range from about 25 mm to about 75 mm, or about 40 mm. The maximum diameter of the support cap 212 in the deployed state can range from about 25 mm to about 60 mm, preferably about 35 mm to 45 mm.

In some embodiments, the legs 214 include flexible tines, which may be formed from a flexible or shape memory material, such as nickel titanium. The number of legs can range from about 3 to about 8. The length of each leg can range from about 25 mm to about 100 mm, or longer if the deployment mechanism is external to the patient's body. The width and/or thickness, e.g., diameter, of each leg can range from about 0.003 inches to about 0.035 inches.

In some examples, the support cap 212 may be a flexible cover 216 mounted to and supported by the legs 214. The flexible cover 216 may be formed from a flexible, soft, and/or resilient material, such as silicone or Teflon®, a porous material, or a combination thereof, to prevent fluid from passing through the cover 216. In some examples, the flexible material is formed from a material that does not significantly abrade, irritate, or damage the mucosal lining of the bladder wall or urethra when positioned adjacent the mucosal lining, such as a silicone or Teflon® material or a porous material. The thickness of the cover 216 may range from about 0.05 mm to about 0.5 mm. In some examples, the flexible cover 216 and legs 214 are sufficiently structurally rigid such that the cover 216 and legs 214 maintain their shape when contacted by the top wall or bladder tissue 1004. Thus, the legs 214 and flexible cover 216 prevent the bladder from collapsing and blocking the perforations on the retention portion 6 and/or the open distal end 30 of the tube 12. The legs 214 and flexible cover 216 also effectively hold the trigone area and ureteral orifice open so that negative pressure can draw urine into the bladder and drainage tube 12. As discussed herein, if the bladder is allowed to collapse too much, a tissue flap will extend across the ureteral orifice, thereby preventing negative pressure from being transmitted to the ureteral catheter, ureteral stent, and/or ureter, thereby blocking the drawing of urine into the bladder.

In some embodiments, the catheter device 10 further comprises a drain tube 218. As shown in FIG. 1G-1J, the drain tube 218 can comprise an open distal end 220 positioned adjacent to or extending from the open distal end 30 of the tube 12. In some embodiments, the open distal end 220 of the drain tube 218 is the only opening for drawing urine from the bladder into the interior of the drain tube 218. In other embodiments, the distal portion of the drain tube 218 can comprise perforations (not shown in FIG. 1G-1I) or holes, ports, or perforations 174 on its upper sidewall 222, as shown in FIG. 1J. The holes, ports, or perforations 174 can provide additional space for drawing urine into the interior of the drain tube 218, thereby ensuring that fluid collection can continue even if the open distal end 220 of the drain tube 218 is occluded. The holes, ports, or perforations 174 may also increase the surface area available for drawing fluid into the drain 218, thereby increasing efficiency and/or fluid collection yield.

In some embodiments, the distal-most portion of the support cap 212 can include a sponge or pad 224, such as a gel pad. The pad 224 can be positioned to contact and press against the upper bladder wall or bladder tissue 1004 during negative pressure therapy for the purpose of preventing drainage, aspiration, or other trauma to the bladder 10.

1J, the bladder upper wall support 210 comprises a support cap 212 and a plurality of legs 214. As in the previously described embodiments, the bladder upper wall support 210 can be moved between a retracted position in which the support 210 is at least partially retracted within the conduit or tube 12 and a deployed position for supporting the upper wall of the bladder. In some embodiments, the catheter device 10 also includes a drain tube 218 extending from the open distal end 30 of the conduit or tube 12. Unlike the previously described embodiments, the support cap 212 shown in FIG. 4 comprises an inflatable balloon 226. The inflatable balloon 226 can be generally hemispherical and can comprise a curved distal surface 228 configured to contact and support at least a portion of the upper bladder wall or bladder tissue 1004 when deployed.

In some embodiments, the drain tube 218 includes a perforated portion 230 extending between the open distal end 30 of the tube 12 and the support structure 212. The perforated portion 230 is positioned to draw fluid into the interior of the drain tube 218 so that it can be removed from the bladder 100. Desirably, the perforated portion 230 is positioned so that it is not blocked by either the deployed support cap 212 or the bladder wall when negative pressure is applied thereto. The drain tube 218 can include or be positioned adjacent to an inflation lumen 232 for providing fluid or gas to the interior 234 of the balloon 226 to inflate the balloon 226 from its contracted position to its deployed position. For example, as shown in FIG. 1J, the inflation lumen 232 can be disposed within the drain tube 218.

1K, an exemplary retention portion 6, 123 of a urine collection catheter device 10 is illustrated that includes multiple coiled drain lumens, generally represented as lumens 218. The retention portion 6 comprises a tube 12 having a distal open end 30. The drain lumens 218 are positioned partially within the tube 12. In the deployed position, the drain lumens 218 are configured to extend from the open distal end 30 of the tube 12 and conform to a coiled orientation. The drain lumens 218 may be separate throughout the length of the catheter device 10 or may be telescoped into a single drain lumen defined by the tube 12. In some embodiments, as shown in FIG. 6, the drain lumen 218 may be a pigtail coil having one or more coils 244. Unlike the embodiments described above, the pigtail coil 244 is coiled about an axis that is not coextensive with the axis C of the non-coiled portion of the tube. Alternatively, as shown in FIG. 6, the pigtail coil may be coiled about an axis D that is generally perpendicular to the axis C of the tube 12. In some embodiments, the drain lumen 218 may include holes, ports, or perforations (not shown in FIG. 1K) similar to the perforations 132, 133 of FIG. 9A or 9B to draw fluid from the bladder into the interior of the drain lumen 218. In some embodiments, the perforations may be located on the radially inwardly facing side 240 and/or the outwardly facing side of the coiled portion of the drain lumen. As explained above, perforations located on the radially inwardly facing side of the drain lumen 218 or tube 12 are less likely to be blocked by the bladder wall during application of negative pressure to the bladder. Urine may also be drawn directly into one or more drain lumens defined by the tube 12. For example, rather than being drawn into the drain lumen 218 through the perforations 230, urine can be drawn directly through the open distal end 30 into the drain lumen defined by the tube 12.

1L and 1M, another embodiment of the retention portion 123 is shown. The fluid receiving portion or distal end portion 30a of the catheter device 10a is shown in a contracted position in FIG. 1L and in a deployed position in FIG. 1M. The distal end 30a includes opposing bladder wall supports 19a, 19b for supporting the upper or lower bladder wall 1004. For example, the distal end portion 30a can include a proximal sheath 20a and a distal sheath 22a. Each sheath 20a, 22a extends between a slidable ring or collar 24a and a stationary or mounting ring or collar 28a. The sheaths 20a, 22a are formed from a flexible, non-porous material, such as silicone or any of the materials discussed herein. The sheaths 20a, 22a are held together by one or more flexible wires or cables 26a. The sheaths 20a, 22a can also be connected by one or more rigid members, such as supports 32a. In some examples, the supports 32a can be tines formed from a flexible shape memory material such as nickel titanium. The supports 32a are positioned to provide support for the proximal sheath 20a and to prevent the distal end 30a from collapsing when in the deployed position. In the retracted position, the collars 24a, 28a are positioned away from each other such that the sheaths 20a, 22a are stretched or folded relative to the cable 26a and the supports 32a. In the deployed position, the slidable collar 24a is moved toward the stationary collar 28a, allowing the sheaths 20a, 22a to unfold from the central cable 26a and form a generally flat, disk-shaped structure.

In use, the distal end 30a of the catheter device 10a is inserted into the patient's bladder in a contracted position. Once inserted into the bladder, the distal sheath 22a is released by sliding the slidable collar 24a distally towards the stationary collar 28a. Once the distal sheath 22a is deployed, the proximal sheath 20a is released or deployed in a similar manner by sliding the slidable collar 24a proximally towards the respective stationary collar 28a. At this point, the proximal sheath 20a is floating within the bladder and is not positioned or sealed against the lower wall of the bladder. Pressure on the distal sheath 22a caused by the collapse of the bladder is transmitted through the support 32a to the proximal sheath 20a, moving the proximal sheath 20a towards a desired position adjacent the opening of the urethra. Once the proximal sheath 20a is in position, a seal across the urethral opening may be created. The proximal sheath 20a helps maintain a negative pressure within the bladder and prevents air and/or urine from exiting the bladder through the urethra.

Referring to Figures 1N-1T, the retention portion 123 comprises an inflatable support cap, such as an annular balloon 310, positioned to contact the upper wall of the bladder 10 and prevent the bladder 10 from constricting and obstructing either the fluid port 312 of the catheter device 10 or the ureteral opening of the bladder. In some embodiments, the distal end portion 30 of the tube 12 extends through the central opening 314 of the balloon 310. The distal end portion 30 of the tube 12 can also contact the upper bladder wall.

Now referring to 1N and 1O, in some embodiments, the tube 12 includes a fluid access portion 316 positioned proximal to the balloon 310 and extending through a sidewall of the tube 12. The fluid access portion 316 can include a filter 318 (shown in FIG. 1O) disposed about the central lumen of the tube 12. In some embodiments, a sponge material 320 can be positioned over the filter 318 for increased absorption of fluids within the bladder. For example, the sponge material 320 can be injection molded over the filter 318. In use, urine is absorbed by the sponge material 320 and passes through the filter 318 into the central lumen of the tube 12 in response to application of negative pressure through the tube 12.

Now referring to Figures 1P-1R, in another embodiment, a support cap, such as an annular balloon 310, includes a generally spherical distal portion 322 configured to contact and support the upper bladder wall. The balloon 310 further includes a plurality of proximally extending lobes 324. For example, the balloon 310 can include three lobes 324 spaced equidistantly around a portion of the tube 12 proximal to the balloon 310. As shown in Figure 1R, the fluid port 312 can be positioned between adjacent lobes 324. In this configuration, the lobes 324 and the spherical distal portion 322 contact the bladder wall, which prevents the bladder wall from obstructing or blocking the fluid port 312.

1S and 1T, in another embodiment, the annular balloon 310 has a flattened or elongated shape. For example, the annular balloon 310 can have a generally teardrop-shaped radial cross-section as shown in FIG. 1T, with a narrower portion 326 thereof positioned adjacent the tube 12 and an enlarged or bulbous portion 328 positioned on its radially outwardly facing side. The flattened annular balloon 310 is configured to span and, optionally, seal the periphery of the trigone region of the bladder when deployed within the bladder, such that the outer periphery of the balloon 310 extends radially beyond the ureteral opening. For example, when positioned within the patient's bladder, the central opening 314 of the balloon 310 can be configured to be positioned above the trigone region. The fluid port 312 can be positioned proximal to the central portion balloon 310, as shown in FIG. 1T. Desirably, the fluid port 312 is positioned between the central opening 314 of the balloon and the trigone region. When the bladder contracts from the application of negative pressure, the bladder wall is supported by the periphery of the balloon 310 to avoid obstructing the ureteral orifices. Thus, in this configuration, the balloon 310 contacts the bladder wall and prevents it from obstructing or blocking the fluid port 312. Similarly, as discussed herein, the balloon 310 keeps the trigone region open so that urine can be drawn from the ureters through the ureteral orifices and into the bladder.

Referring to FIG. 41, in another embodiment of the bladder catheter, an expandable cage 530 can anchor the bladder catheter within the bladder. The expandable cage 530 comprises a plurality of flexible members or tines extending longitudinally and radially outward from the catheter body of the bladder catheter, which in some embodiments can be similar to those discussed above with respect to the retention portion of the ureteral catheter of FIG. 41. The members can be formed from a suitable elastic and shape memory material, such as Nitinol. In the deployed position, the members or tines are given sufficient curvature to define a spherical or ellipsoidal central cavity. The cage is attached to the open distal end of the catheter tube or body, allowing access to the drainage lumen defined by the tube or body. The cage is sized for positioning within the lower portion of the bladder and can define a diameter and length ranging from 1.0 cm to 2.3 cm, preferably about 1.9 cm (0.75 inches).

In some embodiments, the cage further comprises a shield or cover over a distal portion of the cage to prevent or reduce the likelihood that tissue, i.e., the distal wall of the bladder, will be trapped or bitten as a result of contact with the cage or member. More specifically, as the bladder contracts, the inner distal wall of the bladder contacts the distal side of the cage. The cover may prevent tissue from being bitten or trapped, reduce patient discomfort during use, and protect the device. The cover may be formed, at least in part, from a porous and/or permeable biocompatible material, such as a woven polymer mesh. In some embodiments, the cover encapsulates all or substantially all of the cavity. In some embodiments, the cover covers only about the distal ⅔, about the distal half, or about the distal ⅓ portion of the cage 210, or any amount.

The cage and cover are transitionable from a contracted position, in which the members are tightly contracted together around the central portion and/or the bladder catheter 116 to allow insertion through the catheter or sheath, to an deployed position. For example, for a cage constructed from a shape memory material, the cage can be configured to transition to the deployed position upon warming to a sufficient temperature, such as body temperature (e.g., 37°C). In the deployed position, the cage preferably has a diameter D that is wider than the urethral opening to prevent patient motion from being transmitted through the ureteral catheter 112, 114 to the ureter. The open arrangement of the members 212 or tines does not obstruct or obstruct the distal opening 248 and/or drainage port of the bladder catheter 216, making it easier to perform manipulations of the catheter 112, 114.

It should be understood that any of the bladder catheters described above may also be useful as ureteral catheters.

The bladder catheter is connected to a vacuum source, such as a pump assembly 710, for example, by flexible tubing 166 which defines a fluid flow path.
Exemplary Fluid Sensors:

1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, in some embodiments, the system or assembly 100, 700, 1100 further comprises one or more sensors 174 for monitoring physical parameters or fluid properties of the fluid or urine being collected from the ureters 6, 8 and/or bladder 10. The one or more physiological sensors 174 associated with the patient can be configured to provide information representative of at least one physical parameter to the controller. As discussed herein in connection with FIG. 44, information obtained from the sensors 174 can be transmitted to a central data collection module or processor and used to control the operation of an external device, such as, for example, a pump 710 (shown in FIG. 44). The sensor 174 can be formed integrally with one or more of the catheters 112, 114, 116, such as, for example, embedded within the walls of the catheter body or tube and in fluid communication with the drainage lumen 124, 140. In other embodiments, one or more of the sensors 174 can be located within the internal circuitry of an external device, such as a fluid collection container 712 (shown in FIG. 44) or a pump 710.

Exemplary sensors 174 that may be used with the urine collection assembly 100 may include one or more of the following sensor types: For example, the catheter assembly 100 may include a conductivity sensor or electrode that samples the conductivity of urine. The normal conductivity of human urine is approximately 5-10 mS/m. Urine with a conductivity outside of the expected range may indicate that the patient is experiencing physiological problems and may require further treatment or analysis. The catheter assembly 100 may also include a flow meter for measuring the flow rate of urine through the catheters 112, 114, 116. The flow rate may be used to determine the total volume of fluid excreted from the body. The catheters 112, 114, 116 may also include a thermometer for measuring urine temperature. The urine temperature may be used in conjunction with the conductivity sensor. The urine temperature may also be used for monitoring purposes, as urine temperature outside of the normal physiological range may indicate certain physiological conditions. In some examples, the sensor 174 may be a urine analyte sensor configured to measure the concentration of creatinine and/or protein in the urine. For example, a variety of conductivity and optical spectroscopy sensors may be used to determine analyte concentrations in urine. Sensors based on color change reagent test strips may also be used for this purpose.
To insert the system:

Having described the system 100, which includes a ureteral catheter and/or ureteral stent and a bladder catheter, several examples of methods for the insertion and deployment of the ureteral stent or ureteral catheter and bladder catheter will now be discussed in detail.

In some embodiments, a method is provided for inducing negative pressure within a portion of a patient's urinary tract, the method including the steps of deploying a ureteral catheter within the patient's ureter to maintain patency of fluid flow between the patient's kidney and bladder, the ureteral catheter having a distal portion for insertion within the patient's kidney and a proximal portion; deploying a bladder catheter within the patient's bladder, the bladder catheter having a distal portion for insertion within the patient's bladder and a proximal portion for application of negative pressure, the proximal portion extending outside the patient's body; and applying negative pressure to a proximal end of the bladder catheter to induce negative pressure within a portion of the patient's urinary tract and remove fluid from the patient. In some embodiments, at least one of the ureteral or bladder catheters comprises (a) a proximal portion and (b) a distal portion comprising one or more protected drains, ports, or perforations and a retention portion configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding the one or more protected drains, ports, or perforations in response to application of negative pressure through the catheter.

42A, an example of steps for positioning the system within a patient's body and optionally inducing negative pressure within the patient's urinary tract, such as the bladder, ureter, and/or kidney, is illustrated. As shown in box 610, a medical professional or caregiver inserts a flexible or rigid cystoscope through the patient's urethra and into the bladder to obtain visualization of the ureteral orifice or opening. Once suitable visualization is obtained, a guidewire is advanced through the urethra, bladder, ureteral orifice, ureter, to a desired fluid collection location, such as the renal pelvis of the kidney, as shown in box 612. Once the guidewire is advanced to the desired fluid collection location, a ureteral stent or catheter of the present invention (examples of which are discussed in detail above) is inserted over the guidewire to the fluid collection location, as shown in box 614. In some examples, the location of the ureteral stent or catheter can be confirmed by fluoroscopy, as shown in box 616. Once the position of the ureteral stent or distal end of the ureteral catheter has been confirmed, the retention portion of the ureteral catheter can be deployed, as shown in box 618. For example, the guidewire can be removed from the catheter, thereby allowing the distal end and/or retention portion to transition to the deployed position. In some embodiments, the deployed distal end portion of the catheter does not completely occlude the ureter and/or renal pelvis, such that urine is permitted to pass from outside the catheter through the ureter and into the bladder. Moving the catheter avoids complete obstruction of the ureter, which may impart forces against urinary tract tissue, and avoids application of forces to the ureteral sidewall, which may cause injury.

After the ureteral stent or catheter is in place and deployed, the same guidewire can be used to position a second ureteral stent or catheter in the other ureter and/or kidney using the same insertion and positioning methods described herein. For example, a cystoscope can be used to obtain visualization of the other ureteral opening in the bladder, and a guidewire can be advanced through the visualized ureteral opening to a fluid collection location in the other ureter. The second ureteral stent or catheter can be pulled along with the guidewire and deployed in the manner described herein. Alternatively, the cystoscope and guidewire can be removed from the body. The cystoscope can be reinserted into the bladder over the first ureteral catheter. The cystoscope is used in the manner described above to obtain visualization of the ureteral opening and to assist in advancing a second guidewire into the second ureter and/or kidney to position the second ureteral stent or catheter. Once the ureteral stent or catheter is in place, in some embodiments the guidewire and cystoscope are removed. In other embodiments, the cystoscope and/or guidewire can remain in the bladder to aid in the placement of the bladder catheter.

In some embodiments, once the ureteral catheter is in place, the healthcare professional, caregiver, or patient can insert the distal end of the bladder catheter in a collapsed or contracted state through the patient's urethra and into the bladder, as shown in box 620. The bladder catheter can be a bladder catheter of the present invention as discussed in detail above. Once inserted into the bladder, the anchors connected to and/or associated with the bladder catheter are expanded to a deployed position, as shown in box 622. In some embodiments, the bladder catheter is inserted through the urethra into the bladder without the use of a guidewire and/or cystoscope. In other embodiments, the bladder catheter is inserted over the same guidewire used to position the ureteral stent or catheter.

In some embodiments, the ureteral stent or ureteral catheter is deployed and remains within the patient's body for at least 24 hours or longer. In some embodiments, the ureteral stent or ureteral catheter is deployed and remains within the patient's body for at least 30 days or longer. In some embodiments, the ureteral stent or ureteral catheter is replaced periodically, for example, weekly or monthly, to extend the duration of therapy.

In some embodiments, the bladder catheter is replaced more frequently than the ureteral stent or ureteral catheter. In some embodiments, multiple bladder catheters are placed and removed consecutively during the indwelling time for a single ureteral stent or ureteral catheter. For example, a physician, nurse, caregiver, or patient can place a bladder catheter in a patient at home or in any healthcare setting. Multiple bladder catheters can be provided to a healthcare professional, patient, or caregiver in a kit, optionally with instructions for placement, replacement, and optional connection of the bladder catheter to a negative pressure source or drainage into a container, as needed. In some embodiments, negative pressure is applied nightly for a predetermined number of nights (e.g., 1-30 or more nights). Optionally, the bladder catheter can be replaced nightly before application of negative pressure.

In some embodiments, urine is allowed to drain by gravity or peristalsis from the urethra. In other embodiments, negative pressure is induced in the bladder catheter to facilitate drainage of urine. Without intending to be bound by any theory, it is believed that a portion of the negative pressure applied to the proximal end of the bladder catheter is transmitted to the ureter, renal pelvis, or other portions of the kidney, facilitating drainage of fluid or urine from the kidney.

Referring to FIG. 42B, steps for using the system for induction of negative pressure in the ureter and/or kidney are illustrated. As shown in box 624, after the ureteral stent or ureteral catheter and the indwelling portion of the bladder catheter are properly positioned and any anchoring/retention structures, if present, are deployed, the external proximal end of the bladder catheter is connected to a fluid collection or pump assembly. For example, the bladder catheter can be connected to a pump to induce negative pressure in the patient's bladder, renal pelvis, and/or kidney.

Once the bladder catheter and pump assembly are connected, negative pressure is applied to the renal pelvis and/or kidney and/or bladder through the drainage lumen of the bladder catheter, as shown in box 626. The negative pressure is intended to counteract the stasis-mediated interstitial hydrostatic pressure resulting from elevated intraperitoneal pressure and resulting or elevated renal venous or lymphatic pressure. The applied negative pressure can thus increase the flow of filtrate through the medullary tubules and decrease water and sodium reabsorption.

As a result of the applied negative pressure, urine is drawn into the bladder catheter at the drain port at its distal end, through the drain lumen of the bladder catheter, and into a fluid collection container for disposal, as shown in box 628. As urine is drawn into the collection container, optional sensors located within the fluid collection system, in box 630, can provide several measurements about the urine that can be used to assess physical parameters such as the volume of urine collected, as well as information about the patient's physical condition and the composition of the urine produced. In some examples, the information obtained by the sensors is processed by a processor associated with the pump and/or another patient monitoring device, as shown in box 632, and displayed to the user via a visual display of an associated feedback device, in box 634.
Exemplary Fluid Collection Systems:

Having described exemplary systems and methods for positioning such systems within a patient's body, a system 700 for inducing negative pressure in a patient's bladder, ureter, renal pelvis, and/or kidney will now be described with reference to FIG. 44. System 700 may comprise a ureteral stent and/or ureteral catheter, bladder catheter, or system 100, as described herein above. As shown in FIG. 44, the bladder catheter 116 of system 100 is connected to one or more fluid collection containers 712 to collect urine drawn from the bladder. The fluid collection containers 712 connected to the bladder catheter 116 may be in fluid communication with an external fluid pump 710 to generate negative pressure through the bladder catheter 116 and/or ureteral catheters 112, 114 within the bladder, ureter, and/or kidney. As discussed herein, such negative pressure may be provided to overcome interstitial pressure and form urine within the kidney or renal unit. In some examples, the connection between the fluid collection container 712 and the pump 710 can include a fluid lock or fluid barrier to prevent air from entering the bladder, renal pelvis, or kidney in the event of an accidental therapeutic or non-therapeutic pressure change. For example, the inflow and outflow ports of the fluid container can be positioned below the fluid level in the container. Thus, air is prevented from entering the medical tubing or catheter through either the inflow or outflow ports of the fluid container 712. As discussed above, the exterior portion of the tubing extending between the fluid collection container 712 and the pump 710 can include one or more filters to prevent urine and/or particulate matter from entering the pump 710.

As shown in FIG. 44, the system 700 further includes a controller 714, such as a microprocessor, electronically coupled to the pump 710 and having or associated with a computer-readable memory 716. In some embodiments, the memory 716 includes instructions that, when executed, cause the controller 714 to receive information from a sensor 174 located on or associated with a portion of the assembly 100. Information about the patient's condition can be determined based on the information from the sensor 174. Information from the sensor 174 can also be used to determine and implement operating parameters for the pump 710.

In some examples, the controller 714 is incorporated within a separate and remote electronic device that communicates with the pump 710, such as a dedicated electronic device, computer, tablet PC, or smartphone. Alternatively, the controller 714 can be included within the pump 710 and can control both a user interface for manually operating the pump 710 and system functions, such as receiving and processing information from the sensor 174.

The controller 714 is configured to receive information from one or more sensors 174 and store the information in an associated computer-readable memory 716. For example, the controller 714 can be configured to receive information from the sensors 174 at a predetermined rate, such as once per second, and determine the conductivity based on the received information. In some examples, the algorithm for calculating the conductivity can also include other sensor measurements, such as urine temperature, to obtain a more robust determination of the conductivity.

The controller 714 can also be configured to calculate patient physical statistics or diagnostic indicators illustrating changes in the patient's condition over time. For example, the system 700 can be configured to identify the total amount of sodium excreted. The total amount of sodium excreted can be based, for example, on a combination of flow rate and conductivity over a period of time.

Continuing with reference to FIG. 44, the system 700 can further include a feedback device 720, such as a visual display or audio system, to provide information to the user. In some examples, the feedback device 720 can be formed integrally with the pump 710. Alternatively, the feedback device 720 can be a separate dedicated or multi-purpose electronic device, such as a computer, laptop computer, tablet PC, smartphone, or other handheld electronic device. The feedback device 720 is configured to receive calculated or determined measurements from the controller 714 and present the received information to the user via the feedback device 720. For example, the feedback device 720 may be configured to display the current negative pressure (in mmHg) being applied to the urinary tract. In other examples, the feedback device 720 is configured to display the current flow rate of urine, the temperature, the current conductivity of urine in mS/m, the total urine volume produced during the session, the total sodium excreted during the session, other physical parameters, or any combination thereof.

In some examples, the feedback device 720 further comprises a user interface module or component that allows a user to control the operation of the pump 710. For example, the user can turn the pump 710 on or off via the user interface. The user can also adjust the pressure applied by the pump 710 to achieve a greater magnitude or rate of sodium excretion and fluid removal.

Optionally, the feedback device 720 and/or pump 710 further comprises a data transmitter 722 for transmitting information from the device 720 and/or pump 710 to other electronic devices or computer networks. The data transmitter 722 can utilize short-range or long-range data communication protocols. An example of a short-range data transmission protocol is Bluetooth. Long-range data transmission networks include, for example, Wi-Fi or cellular networks. The data transmitter 722 can transmit information to the patient's physician or caregiver to inform the physician or caregiver of the patient's current condition. Alternatively or in addition, the information can be transmitted from the data transmitter 722 to an existing database or information storage location, for example, to include information to be recorded in the patient's electronic medical record (EHR).

Continuing with reference to FIG. 44, in addition to the urine sensor 174, in some embodiments, the system 700 can further include one or more patient monitoring sensors 724. The patient monitoring sensors 724 can include invasive and non-invasive sensors to measure information about the patient's physical parameters, such as urine composition, blood composition (e.g., hematocrit percentage, analyte concentration, protein concentration, creatinine concentration), and/or blood flow (e.g., blood pressure, blood flow rate), as discussed in detail above. Hematocrit is the ratio of red blood cell volume to total blood volume. Normal hematocrit is about 25%-40%, preferably about 35% and 40% (e.g., 35%-40% red blood cells and 60%-65% plasma by volume).

The non-invasive patient monitoring sensors 724 may include pulse oximetry sensors, blood pressure sensors, heart rate sensors, and respiration sensors (e.g., capnography sensors). The invasive patient monitoring sensors 724 may include invasive blood pressure sensors, glucose sensors, blood velocity sensors, hemoglobin sensors, hematocrit sensors, protein sensors, creatinine sensors, and others. In yet other examples, the sensors may be associated with an extracorporeal blood system or circuit and configured to measure parameters of blood passing through tubing of the extracorporeal system. For example, an analyte sensor, such as a capacitance sensor or an optical spectroscopy sensor, may be associated with tubing of the extracorporeal blood system and measure parameter values of the patient's blood as it passes through the tubing. The patient monitoring sensors 724 may communicate wired or wirelessly with the pump 710 and/or the controller 714.

In some examples, the controller 714 is configured to cause the pump 710 to provide therapy for patient-based information obtained from a urine analyte sensor 174, such as a blood monitoring sensor, and/or a patient monitoring sensor 724. For example, the operating parameters of the pump 710 can be adjusted based on changes in the patient's blood hematocrit rate, blood protein concentration, creatinine concentration, urination volume, urine protein concentration (e.g., albumin), and other parameters. For example, the controller 714 can be configured to receive information about the patient's blood hematocrit rate or creatinine concentration from the patient monitoring sensor 724 and/or the analyte sensor 174. The controller 714 can be configured to adjust the operating parameters of the pump 710 based on the blood and/or urine measurements. In other examples, the hematocrit rate may be measured from blood samples obtained periodically from the patient. The results of the tests can be provided to the controller 714, either manually or automatically, for processing and analysis.

As discussed herein, the measured hematocrit value for the patient can be compared to a predetermined threshold or clinically acceptable value for the general population. Generally, hematocrit levels for women are lower than those for men. In other examples, the measured hematocrit value can be compared to a patient baseline value obtained prior to the surgical procedure. Once the measured hematocrit value has increased within an acceptable range, the pump 710 may be turned off and cease applying negative pressure to the ureter or kidney. Similarly, the intensity of the negative pressure can be adjusted based on the measured parameter values. For example, as the patient's measured parameters begin to approach an acceptable range, the intensity of the negative pressure being applied to the ureter and kidney can be reduced. In contrast, if an undesirable trend (e.g., a decrease in hematocrit value, urination rate, and/or creatinine clearance) is identified, the intensity of the negative pressure can be increased to produce a positive physiological outcome. For example, the pump 710 may be configured to begin by providing a low level of negative pressure (e.g., between about 0.1 mmHg and 10 mmHg). The negative pressure may be gradually increased until a positive trend in the patient creatinine level is observed. Generally, however, the negative pressure provided by the pump 710 will not exceed about 50 mmHg.

45A and 45B, an exemplary pump 710 for use with the system is illustrated. In some embodiments, the pump 710 is a micropump configured to draw fluid from the catheters 112, 114 (e.g., as shown in Figs. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B) and has a sensitivity or accuracy of about 10 mmHg or less. Desirably, the pump 710 is capable of providing a urine flow range of 0.05 ml/min to 3 ml/min over an extended period of time, e.g., from about 8 hours to about 24 hours/day, 1 to about 30 days, or longer. At 0.2 ml/min, it is expected that about 300 mL of urine/day will be collected by the system 700. The pump 710 can be configured to provide a negative pressure to the patient's bladder, ranging from about 0.1 mmHg to about 150 mmHg, or from about 0.1 mmHg to about 50 mmHg, or from about 5 mmHg to 20 mmHg (gauge pressure at the pump 710). For example, a micropump manufactured by Langer Inc. (Model BT100-2J) can be used with the system 700 of the present disclosure. Diaphragm aspirator pumps as well as other types of commercially available pumps can also be used for this purpose. Peristaltic pumps can also be used with the system 700. In other examples, a piston pump, vacuum bottle, or manual vacuum source can be used to provide the negative pressure. In other examples, the system can be connected to a wall suction source, such as those available in hospitals, through a vacuum regulator to reduce the negative pressure to a therapeutically appropriate level.

In some examples, at least a portion of the pump assembly can be positioned within the patient's urinary tract, e.g., within the bladder. For example, the pump assembly can include a pump module and a control module coupled to the pump module, the control module configured to direct movement of the pump module. At least one (or more) of the pump module, the control module, or the power source may be positioned within the patient's urinary tract. The pump module can include at least one pump element positioned within the fluid flow channel and drawing fluid through the channel. Some examples of suitable pump assemblies, systems, and methods of use are disclosed in U.S. Patent Application No. 62/550,259, entitled "Indwelling Pump for Facilitating Removal of Urine from the Urinary Tract," filed August 25, 2017, which is incorporated herein by reference in its entirety.

In some embodiments, the pump 710 is configured for long-term use and is therefore capable of maintaining fine suction for, for example, about 8 hours to about 24 hours/day, or 1 to about 30 days, or longer, excluding bladder catheter replacement times. Additionally, in some embodiments, the pump 710 is configured to be operated manually and includes a control panel 718 that allows a user to set a desired suction value. The pump 710 can also include a controller or processor, which may be the same controller that operates the system 700, or may be a separate processor dedicated to the operation of the pump 710. In either case, the processor is configured to receive instructions both for manual operation of the pump and for automatically operating the pump 710 according to predetermined operating parameters. Alternatively or in addition, the operation of the pump 710 can be controlled by the processor based on feedback received from multiple sensors associated with the catheter.

In some embodiments, the processor is configured to operate the pump 710 intermittently. For example, the pump 710 may be configured to issue pulses of negative pressure followed by periods during which no negative pressure is provided. In other embodiments, the pump 710 can be configured to alternate between providing negative and positive pressure, resulting in an alternating flush and pump effect. For example, a positive pressure of about 0.1 mmHg to 20 mmHg, preferably about 5 mmHg to 20 mmHg, can be provided followed by a negative pressure ranging from about 0.1 mmHg to 50 mmHg.

Steps for removing excess fluid from a patient using the devices and systems described herein are illustrated in FIG. 49. As shown in FIG. 49, a method of treatment includes deploying a urinary catheter, such as a ureteral stent or ureteral catheter, within the patient's ureter and/or kidney so that urine flows from the ureter and/or kidney, as shown in box 910. The catheter may be positioned to avoid blocking the ureter and/or kidney. In some examples, the fluid collection portion of the stent or catheter may be positioned within the renal pelvis of the patient's kidney. In some examples, the ureteral stent or ureteral catheter may be positioned within each of the patient's kidneys. In other examples, the urine collection catheter may be deployed within the bladder or ureter, as shown in box 911. In some examples, the ureteral catheter comprises one or more of any of the retention portions described herein. For example, the ureteral catheter can comprise a tube defining a drainage lumen with a spiral retention portion and multiple drainage ports. In other examples, the catheter can comprise a funnel-shaped fluid collection and retention portion or a pigtail coil. Alternatively, a ureteral stent, for example with a pigtail coil, can be deployed.

As shown in box 912, the method further includes applying negative pressure through the bladder catheter to at least one of the bladder, ureters, and/or kidneys to induce or promote fluid or urine production in the kidneys and extract the fluid or urine from the patient. Desirably, the negative pressure is applied for a period of time sufficient to reduce the patient's blood creatinine level by a clinically significant amount.

The negative pressure may continue to be applied for a predetermined period of time. For example, the user may be instructed to operate the pump for a period of time selected based on the duration of the surgical procedure or the physiological characteristics of the patient. In other examples, the patient condition may be monitored to determine when sufficient therapy has been provided. For example, as shown in box 914, the method may further include monitoring the patient and determining when to stop applying negative pressure to the patient's bladder, ureters, and/or kidneys. In some examples, the patient's hematocrit level is measured. For example, a patient monitoring device may be used to periodically obtain a hematocrit value. In other examples, blood samples may be taken periodically to directly measure the hematocrit. In some examples, the concentration and/or volume of urine that is drained from the body through the bladder catheter may also be monitored to determine the rate at which urine is being produced by the kidneys. Similarly, drained urine may also be monitored to determine the protein concentration and/or creatinine clearance rate for the patient. Reduced creatinine and protein concentrations in the urine may indicate hyperdilution and/or reduced renal function. The measured value can be compared to a predetermined threshold to assess whether negative pressure therapy improves the patient's condition and whether it should be modified or discontinued. For example, as discussed herein, a desirable range for patient hematocrit may be 25%-40%. In another example, patient weight may be measured and compared to dry weight, as described herein. A change in the measured patient weight demonstrates that fluid is being removed from the body. Thus, a return to dry weight indicates that hemodilution is being properly managed and the patient is not overdiluted.

As shown in box 916, the user may cause the pump to stop providing negative pressure therapy once a positive result is identified. Similarly, patient blood parameters may be monitored to assess the effectiveness of the negative pressure being applied to the patient's kidneys. For example, capacitance or analyte sensors may be placed in fluid communication with the tubing of the extracorporeal blood management system. The sensors may be used to measure information representative of blood protein, oxygen, creatinine, and/or hematocrit levels. The measured blood parameter values may be measured continuously or periodically and compared to various thresholds or clinically acceptable values. Negative pressure may continue to be applied to the patient's bladder, kidneys, or ureters until the measured parameter values are within a clinically acceptable range. Once the measured values are within the thresholds or clinically acceptable range, application of negative pressure may be stopped, as shown in box 916.

In some examples, a method is provided for removing excess fluid from a patient for systemic fluid volume management associated with chronic edema, hypertension, chronic kidney disease, and/or acute heart failure. According to another aspect of the present disclosure, a method is provided for removing excess fluid for a patient undergoing a resuscitation procedure, such as coronary artery graft bypass surgery, by removing excess fluid from the patient. During resuscitation, a solution, such as a saline solution and/or a starch solution, is introduced into the patient's bloodstream by a suitable fluid delivery process, such as an intravenous drip. For example, in some surgical procedures, a patient may be provided with a normal daily intake of fluid 5-10 times. Fluid replacement or resuscitation fluids may be provided to replenish fluids lost through sweating, bleeding, dehydration, and similar processes. In the case of surgical procedures such as coronary artery graft bypass, resuscitation fluids are provided to help maintain the patient's fluid balance and blood pressure within the proper rate. Acute kidney injury (AKI) is a known complication of coronary artery graft bypass surgery. AKI is associated with prolonged hospital stays and increased morbidity and mortality, even in patients who do not progress to renal failure. See Kim, et al., Relationship between a perioperative intravenous fluid administration strategy and acute kidney injury following off-pump coronary artery bypass surgery: an observational study, Critical Care 19:350 (1995). Introducing fluid into the blood also reduces hematocrit levels, which has been shown to further increase mortality and morbidity. Studies have also demonstrated that introducing saline solutions into patients can reduce renal function and/or thwart the natural fluid management process. Therefore, proper monitoring and control of renal function can produce improved outcomes, particularly reducing postoperative cases of AKI.

A method of treating a patient to remove excess fluid is illustrated in FIG. 50. As shown in box 1010, the method includes deploying a ureteral stent or ureteral catheter within the patient's ureter and/or kidney such that urine flow from the ureter and/or kidney is not impeded by an obstruction in the ureter and/or kidney. For example, the distal end of the ureteral stent or fluid collection portion of the catheter may be positioned within the renal pelvis. In other examples, the catheter may be deployed within the kidney or ureter. The catheter may comprise one or more of the ureteral catheters described herein. For example, the catheter may comprise a tube defining a drainage lumen and including a helical retention portion and multiple drainage ports. In other examples, the catheter may include a pigtail coil.

As shown in box 1012, a bladder catheter can be deployed within the patient's bladder. For example, the bladder catheter may be positioned to at least partially seal the urethral opening and prevent the passage of urine through the urethra from the body. The bladder catheter can include an anchor, for example, to maintain the distal end of the catheter within the bladder. As described herein, coils and other arrangements such as helices, funnels, etc., may be used to obtain proper positioning of the bladder catheter. The bladder catheter can be configured to collect fluids that have entered the patient's bladder prior to placement of the ureteral catheter, as well as fluids that are collected from the ureter, ureteral stent, and/or ureteral catheter during treatment. The bladder catheter may also collect urine that flows past the fluid collection portion of the ureteral catheter and enters the bladder. In some examples, a proximal portion of the ureteral catheter may be positioned within the drainage lumen of the bladder catheter. Similarly, the bladder catheter may be advanced into the bladder using the same guidewire used to position the ureteral catheter. In some embodiments, negative pressure may be provided to the bladder through the drainage lumen of the bladder catheter. In other embodiments, negative pressure may be applied to the bladder catheter only, in which case the ureteral catheter drains into the bladder by gravity.

As shown in box 1014, following deployment of the ureteral stent and/or ureteral catheter and bladder catheter, negative pressure is applied to the bladder, ureters, and/or kidneys through the bladder catheter. For example, negative pressure can be applied for a period of time sufficient to extract urine, including some of the fluid provided to the patient during a resuscitation procedure. As described herein, the negative pressure can be provided by an external pump connected to a proximal end or port of the bladder catheter. The pump can be operated continuously or periodically, depending on the patient's therapy requirements. In some cases, the pump may alternate between applying negative and positive pressure.

The negative pressure may continue to be applied for a predetermined period of time. For example, the user may be instructed to operate the pump for a period of time selected based on the duration of the surgical procedure or the physiological characteristics of the patient. In other examples, the patient condition may be monitored to determine when a sufficient amount of fluid has been withdrawn from the patient. For example, as shown in box 1016, fluid draining from the body may be collected and the total volume of fluid obtained may be monitored. The pump may then continue to operate until a predetermined volume of fluid has been collected from the ureteral and/or bladder catheter. The predetermined volume of fluid may be based, for example, on the volume of fluid provided to the patient prior to and during the surgical procedure. As shown in box 1018, application of negative pressure to the bladder, ureters, and/or kidneys is stopped when the total volume of fluid collected exceeds a predetermined volume of fluid.

In other examples, the operation of the pump can be determined based on a measured physiological parameter of the patient, such as a measured creatinine clearance, blood creatinine level, or hematocrit rate. For example, as shown in box 1020, urine collected from the patient may be analyzed by one or more sensors associated with the catheter and/or pump. The sensor can be a capacitance sensor, an analyte sensor, an optical sensor, or a similar device configured to measure urine analyte concentration. Similarly, as shown in box 1022, the patient's blood creatinine or hematocrit level may be analyzed based on information obtained from the patient monitoring sensors discussed herein above. For example, a capacitance sensor may be installed in an existing extracorporeal blood system. The information obtained by the capacitance sensor may be analyzed to determine the patient's hematocrit rate. The measured hematocrit rate may be compared to some expected or therapeutically acceptable value. The pump may continue to apply negative pressure to the patient's ureter and/or kidney until a measured value within the therapeutically acceptable range is obtained. Once a therapeutically acceptable value has been obtained, the application of negative pressure may be stopped, as shown in box 1018.

In other examples, the patient weight may be measured to assess whether fluid is being removed from the patient by the negative pressure therapy being applied, as shown in box 2024. For example, the patient's measured body weight (including fluids introduced during resuscitation procedures) can be compared to the patient's dry weight. As used herein, dry weight is defined as a normal weight measured when the patient is not overdiluted. For example, a patient who is not suffering from one or more of elevated blood pressure, drowsiness or muscle cramps, swelling around the legs, feet, arms, hands, or eyes, and who is breathing comfortably, is likely not to have excess fluid. The weight measured when the patient is not suffering from such symptoms may be the dry weight. The patient weight can be measured periodically until the measured weight approaches the dry weight. Once the measured weight is approached (e.g., within 5% to 10% of the dry weight), the application of negative pressure can be stopped, as shown in box 1018.

The foregoing details of treatment using the system of the present invention can be used to treat a variety of medical conditions that may benefit from increased urine or fluid output or removal. For example, a method is provided for preserving renal function by application of negative pressure, reducing interstitial pressure within the tubules of the medullary region, promoting urination, and preventing venous stasis-induced renal unit hypoxia within the medulla of the kidney. The method includes deploying a ureteral stent or catheter within the patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder, deploying a bladder catheter within the patient's bladder, the bladder catheter comprising a drainage lumen portion having a distal end and a proximal end configured to be positioned within the patient's bladder, and a sidewall extending therebetween, and applying negative pressure to the proximal end of the catheter to induce negative pressure within a portion of the patient's urinary tract for a predetermined period of time and removing fluid from the patient's urinary tract.

In another embodiment, a method for treating acute kidney injury due to venous stasis is provided. The method includes deploying a ureteral stent or ureteral catheter in a patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder; deploying a bladder catheter in the patient's bladder, the bladder catheter having a distal end configured to be positioned within the patient's bladder, a drainage lumen portion having a proximal end and a sidewall extending therebetween; and applying a negative pressure to the proximal end of the catheter to induce a negative pressure within a portion of the patient's urinary tract for a predetermined period of time and remove fluid from the patient's urinary tract, thereby reducing venous stasis in the kidney and treating the acute kidney injury.

In another embodiment, a method is provided for the treatment of New York Heart Association (NYHA) Class III and/or Class IV heart failure through reduction of venous stasis in the kidney. The method includes deploying a ureteral stent or catheter in the patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder, deploying a bladder catheter in the patient's bladder, the bladder catheter having a distal end configured to be positioned in the patient's bladder, a drainage lumen portion having a proximal end and a sidewall extending therebetween, and applying a negative pressure to the proximal end of the catheter to induce a negative pressure in a portion of the patient's urinary tract for a predetermined period of time to remove fluid from the patient's urinary tract and treat volume overload in NYHA Class III and/or Class IV heart failure.

In another embodiment, a method is provided for the treatment of stage 4 and/or stage 5 chronic kidney disease through the reduction of venous stasis in the kidney. The method includes the steps of deploying a ureteral stent or ureteral catheter in the patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder, deploying a bladder catheter in the patient's bladder, the bladder catheter having a drainage lumen portion having a distal end and a proximal end configured to be positioned in the patient's bladder and a sidewall extending therebetween, and applying a negative pressure to the proximal end of the catheter to induce a negative pressure in a portion of the patient's urinary tract to remove fluid from the patient's urinary tract and reduce venous stasis in the kidney.

In some embodiments, a kit is provided for removing fluid from a patient's urinary tract and/or inducing negative pressure within a portion of the patient's urinary tract. The kit includes a ureteral stent or ureteral catheter with a drainage channel for promoting fluid flow from the ureter and/or kidney through the drainage channel of the ureteral stent or catheter toward the patient's bladder, and a pump with a controller configured to induce negative pressure in at least one of the patient's ureter, kidney, or bladder and draw urine through the drainage lumen of the catheter deployed in the patient's bladder. In some embodiments, the kit further includes at least one bladder catheter. In some embodiments, the kit further includes instructions for one or more of the following: inserting/deploying the ureteral stent and/or ureteral catheter, inserting/deploying the bladder catheter, and operating the pump to draw urine through the drainage lumen of the bladder catheter deployed in the patient's bladder.

In some embodiments, another kit includes a plurality of disposable bladder catheters, each including a drain lumen portion having a proximal end, a distal end configured to be positioned within a patient's bladder and a sidewall extending therebetween, and a retention portion extending radially outward from a portion of the distal end of the drain lumen portion and configured to extend into a deployed position in which the diameter of the retention portion exceeds the diameter of the drain lumen portion, instructions for inserting/deploying the bladder catheter, and instructions for connecting the proximal end of the bladder catheter to a pump and for operating the pump, e.g., by applying negative pressure to the proximal end of the bladder catheter, to draw urine through the drain lumen of the bladder catheter.

In some examples, a kit is provided comprising a plurality of disposable bladder catheters, each bladder catheter comprising: (a) a proximal portion; and (b) a distal portion comprising one or more protected drainage holes, ports, or perforations, the distal portion comprising a retention portion configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure through the catheter; instructions for deploying the bladder catheter; and instructions for connecting the proximal end of the bladder catheter to a pump and for operating the pump to draw urine through the drainage lumen of the bladder catheter.
Experimental Example of Inducing Negative Pressure Using a Ureteral Catheter:

Induction of negative pressure in the renal pelvis of domestic pigs was performed for the purpose of evaluating the effect of negative pressure therapy on renal congestion in the kidney. The purpose of these studies was to demonstrate whether negative pressure delivered into the renal pelvis significantly increases urination in a porcine model of renal congestion. In Example 1, a pediatric Fogarty catheter, typically used in embolectomy or bronchoscopy applications, was used in the porcine model only for proof of principle of induction of negative pressure in the renal pelvis. It is not suggested that the Fogarty catheter be used in humans in a clinical setting to avoid injury to urinary tract tissue. In Example 2, a ureteral catheter 112 was used, as shown in Figures 2A and 2B, and including a spiral retention portion for mounting or maintaining the distal portion of the catheter within the renal pelvis or kidney.

Example 1
Methods Four domestic pigs 800 were used for the purpose of evaluating the effect of negative pressure therapy on renal congestion within the kidney. As shown in FIG. 21, pediatric Fogarty catheters 812, 814 were inserted into the renal pelvic region 820, 821 of each kidney 802, 804 of the four pigs 800. The catheters 812, 814 were deployed within the renal pelvic region by inflating an expandable balloon to a size sufficient to seal the renal pelvis and maintain the position of the balloon within the renal pelvis. The catheters 812, 814 extend from the renal pelvis 802, 804 through the bladder 810 and urethra 816 to a fluid collection container outside the pig.

Urine output from two animals was collected over a 15 minute period to establish a baseline for urination volume and rate. Right kidney 802 and left kidney 804 output were measured individually and found to vary significantly. Creatinine clearance values were also determined.

Renal congestion (e.g., stagnation or reduced blood flow in the renal veins) was induced in the right kidney 802 and left kidney 804 of the animal 800 by partially occluding the inferior vena cava (IVC) with an inflatable balloon catheter 850 just above the renal vein outflow. A pressure sensor was used to measure the IVC pressure. Normal IVC pressure was 1-4 mmHg. By inflating the balloon of the catheter 850 to approximately 3/4 of the IVC diameter, the IVC pressure was raised to 15-25 mmHg. Inflation of the balloon to approximately 3/4 of the IVC diameter resulted in a 50-85% reduction in urination. Complete occlusion produced an IVC pressure of greater than 28 mmHg and was associated with at least a 95% reduction in urination.

One kidney of each animal 800 was not treated and served as a control ("control kidney 802"). A ureteral catheter 812 extending from the control kidney was connected to a fluid collection container 819 to determine fluid levels. One kidney of each animal ("treatment kidney 804") was treated with negative pressure from a negative pressure source (e.g., a therapy pump 818 combined with a regulator designed to more precisely control small magnitudes of negative pressure) connected to the ureteral catheter 814. The pump 818 was an Air Cadet Vacuum Pump manufactured by Cole-Parmer Instrument Company (model number EW-07530-85). The pump 818 was connected in series to a regulator. The regulator was manufactured by Airtrol Components Inc. It was a V-800 Series Miniature Precision Vacuum Regulator-1/8 NPT Ports (model number V-800-10-W/K).

The pump 818 was operated to induce negative pressure in the renal pelvis 820, 821 of the treatment kidney according to the following protocol. First, the effect of negative pressure was investigated under normal conditions (e.g., without inflating the IVC balloon). Four different pressure levels (-2, -10, -15, and -20 mmHg) were applied for 15 minutes each, and the urine produced and the rate of creatinine clearance were determined. The pressure levels were controlled and determined in a regulator. Following the -20 mmHg therapy, the IVC balloon was inflated, increasing the pressure by 15 to 20 mmHg. The same four negative pressure levels were applied. The urine output and creatinine clearance rates for the congested control kidney 802 and the treatment kidney 804 were obtained. The animal 800 was congested by partial occlusion of the IVC for 90 minutes. Treatment was provided for 60 minutes of the 90 minute congestive period.

Following collection of urination and creatinine clearance data, kidneys from one animal underwent macroscopic examination and were then fixed in 10% neutral buffered formalin. Following macroscopic examination, tissue sections were obtained and examined, and magnified images of the sections were captured. Sections were examined using an upright Olympus BX41 light microscope, and images were captured using an Olympus DP25 digital camera. Specifically, light photomicrograph images of sampled tissues were obtained at low magnification (20x original magnification) and high magnification (100x original magnification). The images obtained underwent histological evaluation. The purpose of the evaluation was to histologically examine the tissues and qualitatively characterize congestion and tubular degeneration for the obtained samples.

Surface mapping analysis was also performed on the acquired slides of kidney tissue. Specifically, samples were stained and analyzed to evaluate the difference in tubule size for treated and untreated kidneys. Image processing techniques were used to calculate the number and/or relative percentage of pixels with different coloring in the stained images. The calculated measurement data was used to determine the volume of different anatomical structures.
Outcomes Urinary output and creatinine clearance

Void volume was highly variable. Three sources of variability in voided volume were observed during the study. Inter-individual and hemodynamic variability were expected sources of variability known in the art. A third source of variability in voiding was identified in the experiments discussed herein based on information and ideas previously believed to be unknown, namely, contralateral intra-individual variability in voiding.

Baseline urination volume was 0.79 ml/min for one kidney and 1.07 ml/min for the other kidney (e.g., 26% difference). Urine volume is the average rate calculated from the urination volume per animal.

When stasis was provided by inflating the IVC balloon, therapeutic renal output dropped from 0.79 ml/min to 0.12 ml/min (15.2% of baseline). In comparison, control renal output during stasis dropped from 1.07 ml/min to 0.09 ml/min (8.4% of baseline). Based on the voided volume, the relative increase in therapeutic renal output compared to control renal output was calculated according to the following equation:
(Therapy Treatment/Baseline Treatment)/(Therapy Control/Baseline Control) = Relative Increase (0.12 ml/min/0.79 ml/min)/(0.09 ml/min/1.07 ml/min) = 180.6%

Thus, the relative increase in treated kidney urination volume was 180.6% compared to the control. The results indicate a greater decrease in urine production caused by stasis in the control side compared to the treated side. Presenting the results as a relative percentage difference in urination adjusts for differences in urination between the kidneys.

Creatinine clearance measurements for the baseline, stasis, and treatment portions for one of the animals are shown in FIG.
Gross examination and histological evaluation

Based on gross examination of the control kidney (right kidney) and the treated kidney (left kidney), it was determined that the control kidney had a uniformly dark brown color, which corresponds to more congestion in the control kidney compared to the treated kidney. Qualitative evaluation of the enlarged section images also noted increased congestion in the control kidney compared to the treated kidney. Specifically, as shown in Table 1, the treated kidney exhibited lower levels of congestion and tubular degeneration compared to the control kidney. The following qualitative scale was used for evaluation of the acquired slides:

As shown in Table 1, the treated kidney (left kidney) exhibited only low levels of congestion and tubular degeneration. In contrast, the control kidney (right kidney) exhibited moderate levels of congestion and tubular degeneration. These results were obtained by analysis of the slides discussed below.

Figures 48A and 48B are low and high magnification light micrographs of the left kidney of an animal (treated with negative pressure). Based on histological review, low-grade congestion within the blood vessels at the corticomedullary junction was identified as indicated by the arrow. As shown in Figure 48B, a single tubule with a hyaline cast (as identified by the asterisk) was identified.

Figures 48C and 48D are low and high resolution light micrographs of a control kidney (right kidney). Based on histological review, moderate congestion within the blood vessels at the corticomedullary junction was identified as indicated by the arrow in Figure 48C. As shown in Figure 48D, several tubules with hyaline casts were present in the tissue sample (as identified by the asterisk in the image). The presence of a substantial number of hyaline casts is evidence of hypoxia.

Surface mapping analysis provided the following results: Treated kidneys were determined to have 1.5 times more fluid volume in Bowman's space and 2 times more fluid volume in the tubule lumen. The increased fluid volume in Bowman's space and tubule lumen corresponds to increased urine output. In addition, treated kidneys were determined to have 5 times less blood volume in the capillaries compared to control kidneys. The increased volume in treated kidneys is a result of (1) a decrease in individual capillary size compared to controls and (2) an increase in the number of capillaries without visible red blood cells in treated kidneys compared to control kidneys, an indicator of less congestion in the treated organ.
summary

These results show that the control kidney had more tubules with more congestion and intraluminal hyaline casts, representing protein-rich intraluminal material, compared to the treated kidney. Thus, the treated kidney exhibits a lower degree of loss of renal function. Without intending to be bound by theory, it is believed that as severe congestion develops in the kidney, organ hypoxemia follows. Hypoxemia interferes with oxidative phosphorylation (e.g., ATP production) in the organ. Loss of ATP and/or reduced ATP production blocks active transport of proteins and increases intraluminal protein content, which is expressed as hyaline casts. The number of renal tubules with intraluminal hyaline casts correlates with the degree of loss of renal function. Thus, the reduced number of tubules in the treated left kidney is believed to be physiologically significant. Without intending to be bound by theory, these results are believed to indicate that damage to the kidney can be prevented or inhibited by applying negative pressure to a ureteral catheter inserted into the renal pelvis to promote urination.

Example 2
Methods Four domestic pigs (A, B, C, D) were sedated and anesthetized. Vitals for each pig were monitored throughout the experiment, and cardiac output was measured at the end of each 30-minute phase of the study. A ureteral catheter, such as the ureteral catheter 112 shown in Figures 2A and 2B, was deployed in the renal pelvic region of each kidney of the pig. The deployed catheter was a 6 French catheter with an outer diameter of 2.0 ± 0.1 mm. The catheter was 54 ± 2 cm long, not including the distal retention portion. The retention portion was 16 ± 2 mm long. As shown in the catheter 112 in Figures 2A and 2B, the retention portion included two full coils and one proximal half coil. The outer diameter of the full coil, as shown by line D1 in Figures 2A and 2B, was 18 ± 2 mm. The half coil diameter D2 was approximately 14 mm. The retention portion of the deployed ureteral catheter included six drainage openings, plus an additional opening at the distal end of the catheter tube. The diameter of each of the exhaust openings was 0.83±0.01 mm. The distance between adjacent exhaust openings 132, specifically the linear distance between the exhaust openings when the coil was straightened, was 22.5±2.5 mm.

A ureteral catheter was positioned to extend from the pig's renal pelvis, through the bladder and urethra, and into a fluid collection container external to each pig. Following placement of the ureteral catheter, a pressure sensor was placed in the IVC distal to the renal vein to measure IVC pressure. An inflatable balloon catheter, specifically a PTS® percutaneous balloon catheter (30 mm diameter x 5 cm length) from NuMED Inc. (Hopkinton, NY), was expanded in the IVC proximal to the renal vein. A thermodilution catheter, specifically a Swan-Ganz thermodilution pulmonary artery catheter from Edwards Lifesciences Corp. (Irvine, CA), was then placed in the pulmonary artery for the purpose of measuring cardiac output.

First, baseline urination was measured over 30 minutes and blood and urine samples were collected for biochemical analysis. Following the 30 minute baseline period, the balloon catheter was inflated to increase the IVC pressure from a baseline pressure of 1-4 mmHg to an elevated stasis pressure of approximately 20 mmHg (+/- 5 mmHg). A stasis baseline was then collected over 30 minutes along with corresponding blood and urine analyses.

At the end of the stasis period, elevated stasis IVC pressure was maintained and negative pressure diuretic therapy was provided to pigs A and C. Specifically, pigs (A, C) were treated by applying a negative pressure of -25 mmHg through the ureteral catheter using a pump. As in the examples discussed above, the pump was an Air Cadet Vacuum Pump manufactured by Cole-Parmer Instrument Company (Model No. EW-07530-85). The pump was connected in series to a regulator. The regulator was a V-800 Series Miniature Precision Vacuum Regulator-1/8 NPT Ports (Model No. V-800-10-W/K) manufactured by Airtrol Components Inc. The pigs were observed as treatment was provided over a 120-minute period. Blood and urine collections were performed every 30 minutes during the treatment period. Two of the pigs (B, D) were treated as stasis controls (e.g., no negative pressure was applied to the renal pelvis through the ureteral catheter), meaning that two pigs (B, D) did not receive negative pressure diuretic therapy.

Following collection of urination and creatinine clearance data over the 120 minute treatment period, animals were sacrificed and kidneys from each animal underwent macroscopic examination. Following macroscopic examination, tissue sections were obtained and examined, and magnified images of the sections were captured.
result

Measurements collected during the baseline, stasis, and treatment periods are provided in Table 2. Specifically, voided urine, serum creatinine, and urinary creatinine measurements were obtained at each period. These values allow for the calculation of measured creatinine clearance as follows:
In addition, neutrophil gelatinase-associated lipocalin (NGAL) levels were measured from serum samples obtained at each time point, and kidney injury molecule-1 (KIM-1) levels were measured from urine samples obtained at each time point. Qualitative histological findings determined from review of tissue sections obtained are also included in Table 2.

Animal A: The animal weighed 50.6 kg, had a baseline urinary output of 3.01 ml/min, baseline serum creatinine of 0.8 mg/dl, and measured CrCl of 261 ml/min. Note that these measurements, in addition to serum creatinine, were uncharacteristically high compared to other animals studied. Stasis was associated with a 98% reduction in urinary output (0.06 ml/min) and a >99% reduction in CrCl (1.0 ml/min). Treatment with negative pressure applied through the ureteral catheter was associated with voiding of 17% and 12% of baseline values, respectively, and CrCl of 9-fold and >10-fold of stasis values, respectively. NGAL levels varied throughout the experiment, ranging from 68% of baseline during stasis to 258% of baseline after 90 minutes of therapy. Final values were 130% of baseline. KIM-1 levels were 6 and 4 times baseline over the first two 30-minute time frames after baseline assessment before increasing to 68, 52, and 63 times baseline values over the final three collection periods, respectively. Serum creatinine at 2 hours was 1.3 mg/dl. Histological examination revealed an overall congestion level of 2.4% as measured by blood volume in the capillary space. Histological examination also noted some tubules with intraluminal hyaline casts and some degree of tubular epithelial degeneration, consistent with cellular injury.

Animal B: The animal weighed 50.2 kg and had a baseline urinary output of 2.62 ml/min with a measured CrCl of 172 ml/min (also higher than expected). Stasis was associated with an 80% reduction in urinary output (0.5 ml/min) and an 83% reduction in CrCl (30 ml/min). At 50 minutes into the stasis state (20 minutes after the stasis baseline period), the animal experienced a sudden drop in mean arterial pressure and respiratory rate, followed by tachycardia. The anesthesiologist administered a dose of phenylephrine (75 mg) to prevent cardiogenic shock. Phenylephrine is indicated for intravenous administration when blood pressure drops below a safe level during anesthesia. However, since the experiment was testing the effects of stasis on renal physiology, administration of phenylephrine rendered the remainder of the experiment unintelligible.

Animal C: The animal weighed 39.8 kg, had a baseline urinary output of 0.47 ml/min, baseline serum creatinine of 3.2 mg/dl, and measured CrCl of 5.4 ml/min. Stasis was associated with a 75% reduction in micturition (0.12 ml/min) and a 79% reduction in CrCl (1.6 ml/min). Baseline NGAL levels were determined to be >5-fold the upper limit of normal (ULN). Treatment with negative pressure applied to the renal pelvis through the ureteral catheter was associated with normalization of micturition (101% of baseline) and a 341% improvement in CrCl (18.2 ml/min). NGAL levels varied throughout the experiment, ranging from 84% of baseline during stasis to 47%-84% of baseline between 30 and 90 minutes. Final value was 115% of baseline. KIM-1 levels decreased 40% from baseline within the first 30 minutes of congestion before increasing to 8.7-, 6.7-, 6.6-, and 8-fold baseline values, respectively, over the remaining 30-minute time frame. Serum creatinine levels at the 2-hour time point were 3.1 mg/dl. Histological examination revealed an overall congestion level of 0.9%, as measured by blood volume in the capillary space. Renal tubules were noted to be histologically normal.

Animal D: The animal weighed 38.2 kg, had a baseline voiding rate of 0.98 ml/min, a baseline serum creatinine of 1.0 mg/dl, and a measured CrCl of 46.8 ml/min. Stasis was associated with a 75% reduction in voiding volume (0.24 ml/min) and a 65% reduction in CrCl (16.2 ml/min). Sustained stasis was associated with a 66%-91% reduction in voiding and an 89%-71% reduction in CrCl. NGAL levels varied throughout the experiment, ranging from 127% of baseline during stasis to a final value of 209% of baseline. KIM-1 levels remained 1-2x baseline over the first two 30-minute time frames after baseline assessment before increasing to 190-, 219-, and 201-fold baseline values over the final three 30-minute periods. The 2-hour serum creatinine level was 1.7 mg/dl. Histological examination revealed that the overall congestion level was 2.44-fold greater than that observed in tissue samples for treated animals (A, C) and the average capillary size was 2.33-fold greater than that observed in any of the treated animals. Histological evaluation also noted several tubules with intraluminal hyaline casts as well as tubular epithelial degeneration, indicative of substantial cellular damage.
summary

Without intending to be bound by theory, the data collected are believed to support the hypothesis that venous stasis has a physiologically significant effect on renal function. In particular, it has been observed that an increase in renal venous pressure reduces urination by 75%-98% within seconds. The association between increases in biomarkers of tubular injury and histological damage is consistent with the extent to which venous stasis occurs, both in terms of the magnitude and duration of injury.

The data are also found to support the hypothesis that venous stasis, by altering interstitial pressure, reduces the filtration gradient within the medullary nephrocyte unit. Changes are found to directly contribute to hypoxia and cellular injury within the medullary nephrocyte unit. While this model does not mimic the clinical state of AKI, it certainly provides insight into the mechanical injury sustained.

The data are also seen to support the hypothesis that application of negative pressure to the renal pelvis through a ureteral catheter can increase urination in a venous stasis model. In particular, negative pressure therapy was associated with increases in urination and creatinine clearance that would be clinically significant. Physiologically meaningful decreases in medullary capillary volume and more modest increases in biomarkers of tubular injury were also observed. Thus, it can be seen that by increasing urination volume and decreasing interstitial pressure within the medullary renal unit, negative pressure therapy can directly reduce stasis. Without intending to be bound by theory, it can be concluded that by reducing stasis, negative pressure therapy reduces intrarenal hypoxia and its downstream effects in venous stasis-mediated AKI.

The experimental results are found to support the hypothesis that the degree of stasis, both in terms of the magnitude and duration of pressure, is associated with the degree of cellular injury observed. Specifically, an association between the degree of urination reduction and histological damage was observed. For example, treated pig A, which had a 98% reduction in urination, suffered more damage than treated pig C, which had a 75% reduction in urination. As would be expected, control pig D, which suffered a 75% reduction in urination without the benefit of therapy over two and a half hours, exhibited the most histological damage. These findings are broadly consistent with human data demonstrating an increased risk of developing AKI with more venous stasis. See, for example, Legrand, M. et al. , Association between systematic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study. Critical Care 17:R278-86, 2013.

Example 3
Methods: Induction of negative pressure in the renal pelvis of domestic pigs using a ureteral catheter was performed for the purpose of evaluating the effect of negative pressure therapy on hemodilution of blood. The aim of these studies was to demonstrate whether negative pressure delivered into the renal pelvis significantly increases urination in a porcine model of fluid resuscitation.

Two pigs were sedated and anesthetized using ketamine, midazolam, isoflurane, and propofol. One animal (#6543) was treated with a ureteral catheter and negative pressure therapy as described herein. The other received a Foley-type bladder catheter and served as the control (#6566). Following placement of the ureteral catheter, the animals were transferred to a sleeping platform and monitored for 24 hours.

Volume overload was induced in both animals using a constant infusion of saline (125 mL/hr) for a 24 hour follow-up. Voided volumes were measured every 15 minutes for 24 hours. Blood and urine samples were collected every 4 hours. As shown in Figure 21, the therapy pump 818 was set to induce negative pressure in the renal pelvis 820, 821 of both kidneys (shown in Figure 21) using a pressure of -45 mmHg (+/- 2 mmHg).
result

Both animals received 7 L of saline over a 24 hour period. The treated animals produced 4.22 L of urine while the controls produced 2.11 L. At the end of the 24 hour period, the controls had retained 4.94 L of the 7 L administered while the treated animals had retained 2.81 L of the 7 L administered. Figure 26 illustrates the changes in serum albumin. The treated animals experienced a 6% drop in serum albumin concentration over the 24 hour period while the control animals experienced a 29% drop.
summary

Without intending to be bound by theory, the collected data are believed to support the hypothesis that volume overload induces clinically significant effects on renal function and, as a consequence, hemodilution. In particular, it was observed that the administration of large volumes of intravenous saline cannot be effectively removed, even by healthy kidneys. The resulting fluid accumulation leads to hemodilution. The data are also believed to support the hypothesis that the application of negative pressure diuresis using a ureteral catheter to volume-overloaded animals can increase urination, improve net fluid balance, and reduce the effect of resuscitative fluid administration on the manifestations of hemodilution.

The foregoing examples and embodiments of the present invention have been described with reference to various examples. Modifications and alterations will occur to those skilled in the art upon perusal and understanding of the foregoing examples. Therefore, the foregoing examples should not be construed as limiting the present disclosure.

Claims (66)

1. A ureteral catheter comprising: (a) a proximal portion; and (b) a distal portion, the distal portion comprising a coiled retention portion, the coiled retention portion comprising one or more protected drainage holes, ports, or perforations, the coiled retention portion comprising a plurality of helical coils arranged such that an outer periphery or protective surface area thereof prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure through the ureteral catheter , and a diameter of a distal coil of the coiled retention portion is smaller than a diameter of a proximal coil of the coiled retention portion . 2. The ureteral catheter of claim 1, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the coiled retention portion, and the outer periphery or protected surface area of the coiled retention portion of the ureteral catheter is configured to support the mucosal tissue, thereby preventing occlusion of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the ureteral catheter. 2. The ureteral catheter of claim 1, wherein the coiled retention portion comprises one or more helical coils, each coil having an outwardly facing side and an inwardly facing side, the outer periphery or protected surface area comprises the outwardly facing side of the one or more helical coils, and the one or more protected drain holes, ports, or perforations are disposed on the inwardly facing side of the one or more helical coils. 2. The ureteral catheter of claim 1, wherein the ureteral catheter comprises a drainage lumen portion, and the coiled retention portion is configured to be extended to a deployed position forming a configuration having a diameter greater than a diameter of the drainage lumen portion. 2. The ureteral catheter of claim 1, wherein a number of the drainage holes, ports, or perforations toward a distal end of the coiled retention portion exceeds a number of the drainage holes, ports, or perforations toward a proximal end of the coiled retention portion. 2. The ureteral catheter of claim 1, wherein a size of one or more of the drainage holes, ports, or perforations toward a distal end of the coiled retention portion exceeds a size of one or more of the drainage holes, ports, or perforations toward a proximal end of the coiled retention portion. 2. The ureteral catheter of claim 1, wherein a total area of the drainage holes, ports, or perforations toward a distal end of the coiled retention portion exceeds a total area of the drainage holes, ports, or perforations toward a proximal end of the coiled retention portion. The ureteral catheter of claim 1 , wherein a sidewall of the proximal portion of the ureteral catheter is essentially free or devoid of drainage openings. 1. A system for inducing negative pressure within a portion of a patient's urinary tract, the system comprising:
(a) at least one ureteral catheter comprising a distal portion configured for insertion into a kidney, renal pelvis, and/or ureter of the patient and a proximal portion , the distal portion of the ureteral catheter comprising a coiled retention portion comprising a plurality of helical coils, the distal coil of the coiled retention portion having a diameter smaller than a diameter of a proximal coil of the coiled retention portion;
(b) a bladder catheter comprising a distal portion configured for insertion into the patient 's bladder and a proximal portion configured to transmit negative pressure into the kidney which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter and then outside the patient's body. 10. The system of claim 9, wherein the coiled retention portion comprises one or more protected drainage holes, ports, or perforations, and the plurality of helical coils are arranged such that an outer periphery or protective surface area prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure. 11. The system of claim 10, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the coiled retention portion of the ureteral catheter, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the coiled retention portion of the ureteral catheter, thereby preventing or inhibiting occlusion of one or more of the protected drainage holes, ports, or perforations. The system of claim 9 , wherein the proximal portion of the ureteral catheter is in fluid communication with a distal portion of the bladder catheter. 10. The system of claim 9, wherein the distal portion of the bladder catheter comprises a retention portion comprising one or more protected drainage holes, ports, or perforations and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure. 14. The system of claim 13, wherein the one or more protected drain holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion of the bladder catheter, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the retention portion of the bladder catheter, thereby preventing or inhibiting occlusion of one or more of the protected drain holes, ports, or perforations. 10. The system of claim 9, further comprising a negative pressure source for application of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body. 16. The system of claim 15, wherein the negative pressure source comprises a vacuum source external to the patient's body for application and adjustment of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter , then through the bladder catheter, and then outside the patient's body. 16. The system of claim 15 , wherein the negative pressure received from the negative pressure source is controlled manually, automatically, or a combination thereof. The system of claim 15 , wherein a controller is used to regulate the negative pressure from the negative pressure source. 20. The system of claim 18 , wherein the controller provides an accuracy of about 10 mmHg or less. The system of claim 15 , wherein the negative pressure is provided in a range of about 2 mmHg to about 150 mmHg. The system of claim 9 , further comprising one or more physiological sensors configured to detect at least one physical parameter of the patient. 22. The system of claim 21 , wherein the at least one physical parameter comprises one or more of a volume of collected urine, a urine composition, a urine protein concentration, a blood composition, or a blood flow. 23. The system of claim 22 , wherein the at least one physical parameter of the blood composition comprises one or more of a hematocrit ratio, an analyte concentration, a protein concentration, or a creatinine concentration. 23. The system of claim 22 , wherein the at least one physical parameter of the blood flow comprises one or more of blood pressure or blood flow velocity. 22. The system of claim 21, wherein the one or more physiological sensors comprise one or more of a pulse oximetry sensor, a blood pressure sensor, a heart rate sensor, a respiration sensor, a capnography sensor, a glucose sensor, a blood rate sensor, a hemoglobin sensor, a hematocrit sensor, a protein sensor, a creatinine sensor, an analyte sensor, a capacitance sensor, an optical spectroscopy sensor, or combinations thereof. 1. A system for inducing negative pressure within a portion of a patient's urinary tract, the system comprising:
(a) a ureteral catheter comprising: a distal portion configured for insertion into the patient's kidney, renal pelvis, and/or ureter; and a proximal portion, the distal portion of the ureteral catheter comprising a coiled retention portion, the coiled retention portion comprising a plurality of helical coils, a diameter of a distal coil of the coiled retention portion being smaller than a diameter of a proximal coil of the coiled retention portion;
(b) a bladder catheter, the bladder catheter comprising a distal portion configured for insertion within the patient's bladder and a proximal portion for application of negative pressure, the proximal portion configured to extend outside the patient's body;
(c) a pump, the pump being external to the patient's body due to application of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body. 27. The system of claim 26 , wherein the proximal portion of the ureteral catheter is in fluid communication with the distal portion of the bladder catheter. 27. The system of claim 26, wherein the coiled retention portion comprises one or more protected drainage holes, ports, or perforations, and the plurality of helical coils are arranged such that an outer periphery or protective surface area prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure by the pump. 29. The system of claim 28, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the coiled retention portion of the ureteral catheter, and in response to application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the coiled retention portion of the ureteral catheter, thereby preventing or inhibiting occlusion of one or more of the protected drainage holes, ports, or perforations. 27. The system of claim 26, wherein the distal portion of the bladder catheter comprises a retention portion comprising one or more protected drainage holes, ports, or perforations and configured to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure by the pump. 31. The system of claim 30, wherein the one or more protected drain holes, ports, or perforations are disposed on a protected or inner surface area of the retention portion, and upon application of negative pressure, the mucosal tissue conforms or collapses onto the outer periphery or protected surface area of the retention portion of the bladder catheter, thereby preventing or inhibiting occlusion of one or more of the protected drain holes, ports, or perforations. 27. The system of claim 26 , further comprising one or more physiological sensors configured to detect at least one physical parameter of the patient. 33. The system of claim 32 , wherein the at least one physical parameter comprises one or more of a volume of collected urine, a urine composition, a urine protein concentration, a blood composition, or a blood flow. 34. The system of claim 33 , wherein the at least one physical parameter of the blood composition comprises one or more of a hematocrit ratio, an analyte concentration, a protein concentration, or a creatinine concentration. 34. The system of claim 33 , wherein the at least one physical parameter of the blood flow comprises one or more of blood pressure or blood flow velocity. 33. The system of claim 32, wherein the one or more physiological sensors comprise one or more of a pulse oximetry sensor, a blood pressure sensor, a heart rate sensor, a respiration sensor, a capnography sensor, a glucose sensor, a blood rate sensor, a hemoglobin sensor, a hematocrit sensor, a protein sensor, a creatinine sensor, an analyte sensor, a capacitance sensor, an optical spectroscopy sensor, or combinations thereof. 27. The system of claim 26 , wherein the pump provides an accuracy of about 10 mmHg or less. 27. The system of claim 26 , wherein the negative pressure is provided in a range of about 2 mmHg to about 150 mmHg. 1. A system for inducing negative pressure within a portion of a patient's urinary tract, the system comprising:
(a) at least one ureteral catheter, the at least one ureteral catheter comprising a distal portion for insertion into the patient's kidney, renal pelvis, and/or ureter, and a proximal portion;
(b) a bladder catheter, the bladder catheter comprising a distal portion for insertion into the patient's bladder and a proximal portion for receiving negative pressure from a negative pressure source;
(c) a negative pressure source for application of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into the ureteral catheter, through the bladder catheter, and then outside the patient's body, wherein at least one of the at least one ureteral catheter or bladder catheter comprises (a) a proximal portion and (b) a distal portion, the distal portion comprising a coiled retention portion, the coiled retention portion comprising one or more protected drainage holes, ports, or perforations, the coiled retention portion comprising a plurality of helical coils arranged such that an outer perimeter or protected surface area prevents mucosal tissue from obstructing the one or more protected drainage holes, ports, or perforations in response to application of negative pressure through the at least one of the at least one ureteral catheter or the at least one bladder catheter, and a diameter of the distal coil of the coiled retention portion is smaller than a diameter of a proximal coil of the coiled retention portion . 40. The system of claim 39 , wherein the proximal portion of the at least one ureteral catheter is in fluid communication with the distal portion of the bladder catheter. 40. The system of claim 39, wherein the distal portion of the at least one ureteral catheter comprises a coiled retention portion, the coiled retention portion comprising one or more protected drainage holes, ports, or perforations, the coiled retention portion comprising a plurality of helical coils arranged such that an outer periphery or protective surface area prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure from the negative pressure source. 42. The system of claim 41, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the coiled retention portion of the ureteral catheter, and the outer periphery or protected surface area of the coiled retention portion of the ureteral catheter is configured to support the mucosal tissue, thereby preventing occlusion of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the ureteral catheter. 40. The system of claim 39, wherein the distal portion of the bladder catheter comprises a coiled retention portion, the coiled retention portion comprising one or more protected drainage holes, ports, or perforations, the coiled retention portion comprising a plurality of helical coils arranged such that an outer periphery or protective surface area prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of negative pressure from the negative pressure source. 44. The system of claim 43, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the coiled retention portion of the bladder catheter, and the outer periphery or protected surface area of the coiled retention portion of the bladder catheter is configured to support the mucosal tissue, thereby preventing occlusion of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the bladder catheter. 40. The system of claim 39 , further comprising one or more physiological sensors associated with the patient, the physiological sensors configured to provide information representative of at least one physical parameter to the controller. 40. The system of claim 39, wherein the negative pressure source comprises a pump external to the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body. 40. The system of claim 39, wherein the negative pressure source comprises a vacuum source external to the patient's body for application and adjustment of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the kidney to be drawn into and through the ureteral catheter, then through the bladder catheter, and then outside the patient's body. 48. The system of claim 47 , wherein the vacuum source is selected from the group consisting of a wall suction source, a vacuum bottle, and a manual vacuum source. 48. The system of claim 47 , wherein the vacuum source is provided by a pressure differential. 40. The system of claim 39 , wherein the negative pressure received from the negative pressure source is controlled manually, automatically, or a combination thereof. 40. The system of claim 39 , wherein a controller is used to regulate the negative pressure from the negative pressure source. 47. The system of claim 46 , wherein the pump provides an accuracy of about 10 mmHg or less. 40. The system of claim 39 , wherein the negative pressure is provided in a range of about 2 mmHg to about 150 mmHg. 1. A system for inducing negative pressure within a portion of a patient's urinary tract, the system comprising:
(a) at least one ureteral catheter, the at least one ureteral catheter comprising a distal portion for insertion into the patient's kidney, renal pelvis, and/or ureter, and a proximal portion;
(b) a bladder catheter comprising a distal portion for insertion into the patient's bladder and a proximal portion for receiving negative pressure, the negative pressure causing fluid from the kidney to be drawn into the ureteral catheter, through the bladder catheter, and then outside the patient's body;
11. A system comprising: at least one of the at least one ureteral catheter or the bladder catheter comprising: (a) a proximal portion; and (b) a distal portion, the distal portion comprising a coiled retention portion, the coiled retention portion comprising one or more protected drainage holes, ports, or perforations, the coiled retention portion comprising a plurality of helical coils arranged such that an outer periphery or protective surface area prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of the negative pressure through the at least one ureteral catheter or the bladder catheter, and a diameter of the distal coil of the coiled retention portion is smaller than a diameter of a proximal coil of the coiled retention portion . 55. The system of claim 54 , wherein the proximal portion of the at least one ureteral catheter is in fluid communication with the distal portion of the bladder catheter. 55. The system of claim 54, wherein the distal portion of the at least one ureteral catheter comprises a coiled retention portion, the coiled retention portion comprising one or more protected drainage holes, ports, or perforations, the coiled retention portion comprising a plurality of helical coils arranged such that an outer periphery or protective surface area prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of a pressure differential . 57. The system of claim 56, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the coiled retention portion of the ureteral catheter, and the outer periphery or protected surface area of the coiled retention portion of the ureteral catheter is configured to support the mucosal tissue, thereby preventing occlusion of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the ureteral catheter. 55. The system of claim 54, wherein the distal portion of the bladder catheter comprises a coiled retention portion, the coiled retention portion comprising one or more protected drainage holes, ports, or perforations, the coiled retention portion comprising a plurality of helical coils arranged such that an outer periphery or protective surface area prevents mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations in response to application of the negative pressure. 59. The system of claim 58, wherein the one or more protected drainage holes, ports, or perforations are disposed on a protected or inner surface area of the coiled retention portion of the bladder catheter, and the outer periphery or protected surface area of the coiled retention portion of the bladder catheter is configured to support the mucosal tissue, thereby preventing occlusion of one or more of the protected drainage holes, ports, or perforations in response to application of negative pressure through the bladder catheter. 55. The system of claim 54 , further comprising one or more physiological sensors associated with the patient, the physiological sensors configured to provide information representative of at least one physical parameter to the controller. 1. A kit for inducing negative pressure in a portion of a patient's urinary tract, said kit comprising:
One or two ureteral catheters according to claim 1;
A bladder catheter,
a pump, the pump being external to the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, which in turn causes fluid from the patient's kidneys to be drawn into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then outside the patient's body. 1. A system for inducing negative pressure within a portion of a patient's urinary tract, the system comprising:
a ureteral catheter configured to be deployed within a kidney, renal pelvis, and/or ureter of a patient to maintain patency of fluid flow between the kidney and bladder of the patient, the ureteral catheter comprising a distal portion for insertion within the kidney or renal pelvis of the patient and a proximal portion;
a bladder catheter configured to be deployed within the patient's bladder, the bladder catheter comprising a distal portion for insertion within the patient's bladder and a proximal portion for application of negative pressure, the proximal portion extending outside the patient's body;
and a negative pressure source configured to apply negative pressure to a proximal end of the bladder catheter to induce negative pressure within a portion of the patient's urinary tract to remove fluid from the patient , wherein at least one of the ureteral catheter or the bladder catheter comprises (a) a proximal portion and (b) a distal portion, the distal portion comprising a coiled retention portion, the coiled retention portion comprising one or more protected drains, ports, or perforations, the coiled retention portion comprising a plurality of helical coils arranged such that an outer perimeter or protected surface area prevents mucosal tissue from obstructing the one or more protected drains, ports, or perforations in response to application of negative pressure through the at least one of the ureteral catheter or the bladder catheter, and a diameter of the distal coil of the coiled retention portion is smaller than a diameter of a proximal coil of the coiled retention portion . 63. The system of claim 62 , wherein the urinary catheter is deployed and remains within the patient's body for at least 24 hours. 63. The system of claim 62 , wherein the urinary catheter is deployed and remains within the patient's body for at least 30 days or longer. 63. The system of claim 62 , wherein the bladder catheter and the ureteral catheter are replaceable, and the bladder catheter is replaced more frequently than the ureteral catheter. 63. The system of claim 62 , wherein multiple bladder catheters are placed and removed during the residence time for a single set of ureteral catheters.

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