JP2023015395A - percutaneous urinary catheter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a percutaneous urinary catheter.

SOLUTION: Catheters 112, 114, 116 configured to be deployed in the urinary tract of a patient include a proximal part 117 configured to pass through a percutaneous opening, a retention part 130, and a distal part 118. The distal part is configured to be deployed in the kidney, renal pelvis, and/or bladder of the patient. The retention part includes one or more protected drainage holes, ports or perforations, and is configured, when deployed, to establish an outer periphery 1002 or protection surface area that inhibits mucosal tissue from occluding the one or more protected drainage holes, ports, or perforations upon application of negative pressure through the catheters.

SELECTED DRAWING: Figure 1B

COPYRIGHT: (C)2023,JPO&INPIT

Description

(Cross reference to related applications)
This application is filed January 14, 2016, U.S. Provisional Application No. 62/300,025, filed February 25, 2016, each of which is incorporated herein by reference in its entirety. U.S. Provisional Application No. 62/278,721 filed November 30, 2015; U.S. Provisional Application No. 62/260,966 filed November 30, 2015; U.S. patent application filed Jan. 20, 2017 which is a continuation-in-part of U.S. patent application Ser. 15/411,884, filed January 25, 2018, which is a continuation-in-part of U.S. patent application Ser. No. 16/206,207, filed November 30, 2018, which is a continuation-in-part of US patent application Ser. No. 15/879,770.

Also, U.S. patent application Ser. U.S. Provisional Application No. 62/300,025; U.S. Provisional Application No. 62/278,721 filed January 14, 2016; U.S. Provisional Application No. 62/260 filed November 30, 2015; 966, and U.S. Patent Application No. 15/214,955, filed July 20, 2016, claiming benefit of U.S. Provisional Application No. 62/194,585, filed July 20, 2015. U.S. Patent Application No. 15/411,884, filed Aug. 25, 2017, which is a continuation-in-part of U.S. Patent Application No. 15/411,884, filed Jan. 20, 2017, which is a continuation-in-part of 687,083.

Also, U.S. patent application Ser. U.S. Provisional Application No. 62/300,025; U.S. Provisional Application No. 62/278,721 filed January 14, 2016; U.S. Provisional Application No. 62/260 filed November 30, 2015; 966, and U.S. Provisional Application No. 62/194,585, filed July 20, 2015, in U.S. Serial No. PCT/US2016/043101 filed July 20, 2016; This is a continuation-in-part of US patent application Ser.

Also, U.S. patent application Ser. No. 15/879,770, filed Jan. 25, 2018, U.S. provisional application Ser. It claims the benefit of US Provisional Application No. 62/489,831, filed May 25.

FIELD OF THE DISCLOSURE The present disclosure relates to devices and methods for treating impaired renal function across a variety of disease states and, in particular, to collection of urine and treatment of a patient's urinary tract through percutaneously implanted catheters. It relates to devices and methods for the induction of negative and/or positive pressure within a portion.

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

In normal anatomy, the two kidneys are located retroperitoneally in the abdominal cavity. The kidney is a bean-shaped encapsulated organ. Urine is formed by the renal unit, the functional unit of the kidney, and then flows through a converging tubular system called the collecting duct. The collecting ducts join together to form the minor calyx, then the major calyx, and finally join near the concave portion of the kidney (renal pelvis). The primary function of the renal pelvis is to direct urine flow to the ureters. Urine flows from the renal pelvis into the ureters, tubular structures that carry urine from the kidneys into the bladder. The outer layer of the kidney, called the integument, is a rigid fibrous encapsulation. The inside of the kidney is called the medulla. The medullary structures are arranged pyramidally.

Each kidney consists of approximately one million renal units. Each renal unit contains a glomerulus, Bowman's capsule, and tubules. The tubules include the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, and the collecting duct. The renal units contained within the outer cortical layer of the kidney are distinctly different from the anatomy contained within the medulla. The main difference is the length of Henle's loop. The medullary renal unit contains a longer Henle's loop, which under normal circumstances allows better regulation of water and sodium reabsorption than the integumentary renal unit.

The glomerulus is the origin of the renal unit and is involved in the initial filtration of blood. The afferent arterioles pass blood into the glomerular capillaries where hydrostatic pressure forces water and solutes into Bowman's capsule. The net filtration pressure is expressed as the hydrostatic pressure in the afferent arteriole minus the hydrostatic pressure in the 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 forms in the Bowman's space and is delivered to the renal tubules. The remaining blood exits the glomerulus via the efferent arterioles. Normal glomerular filtration, ie delivery of ultrafiltrate into the tubules, is approximately 90 ml/min/1.73 m ² .

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

Ultrafiltrate that collects in Bowman's space is delivered first to the proximal convoluted tubule. Reabsorption and secretion of water and solutes within the renal tubules are carried out by mixing active transport channels and passive pressure gradients. The proximal convoluted tubule normally reabsorbs most of the sodium chloride and water and nearly all the glucose and amino acids filtered by the glomerulus. Henle's loop has two components designed to concentrate waste in the 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 urine that is concentrated, eg, in terms of urea and creatinine. The distal convoluted tubules normally reabsorb a small proportion of sodium chloride, and osmotic gradients result in water following conditions.

Under normal conditions, the net filtration is approximately 14 mmHg. The effect of venous stasis can be a significant reduction in net filtration up to about 4 mmHg. Jessup M. , The cardiovascular syndrome: Do we need a change of strategy or a change of tactics? , JACC 53(7):597-600, 2009 (hereinafter "Jessup"). A second filtration step occurs in the proximal tubule. Most of the secretion and absorption from urine occurs in the renal tubules within the medullary renal unit. Active transport of sodium from the renal tubules into the interstitial space initiates this process. However, hydrostatic forces dominate the net exchange of solutes and water. Under normal circumstances, 75% of sodium is believed to be reabsorbed into the lymphatic or venous circulation. However, because the kidney is encapsulated, it is sensitive to hydrostatic pressure changes from both venous and lymphatic stasis. During venous stasis, sodium and water retention can exceed 85%, further prolonging renal stasis. Verbrugge et al. , The kidney in congestive heart failure: arenatriuresis, sodium, and diruetucs really the good, the bad and theugly? See European Journal of Heart Failure 2014:16, 133-42 (hereinafter “Verbrugge”).

Venous congestion can lead to the prerenal form of acute kidney injury (AKI). Prerenal AKI results from loss of perfusion (or loss of blood flow) through the kidney. Many clinicians focus on lack of flow into the kidney due to acute circulatory failure conditions. However, there is also evidence that lack of blood flow from an organ due to venous stasis can also be a clinically significant persistent injury. See Damman K, Importance of venous congestion for worsening renal function in advanced decompensated heart failure, JACC 17:589-96, 2009 (hereinafter "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, liver cirrhosis, trauma, burns, and pancreatitis. The symptoms of these disease states have wide clinical variability, but the common denominator is elevated central venous pressure. In ADHF, elevated central venous pressure caused by heart failure leads to pulmonary edema and subsequent dyspnea, thus prompting hospitalization. In sepsis, elevated central venous pressure is primarily the result of large fluid resuscitations. Whether the primary injury is hypovolemia or hypoperfusion due to sodium and fluid retention, the persistent injury is venous stasis, resulting in inadequate perfusion.

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

Since the kidney is an encapsulated organ, it is sensitive to pressure changes within the medullary cones. Increased renal venous pressure results in stasis leading to increased interstitial pressure. Increased interstitial pressure exerts force on both the glomerulus and the renal tubules. See Verbrugge. In the glomerulus, increased interstitial pressure directly opposes filtration. The increase in pressure increases the interstitial fluid, thereby increasing the hydrostatic pressure in the interstitial fluid and peritubular capillaries in the renal medulla. In both cases, hypoxia may ensure that cell injury and further loss of perfusion are led. The net result is further deterioration of sodium and water reabsorption, resulting in negative feedback. See Verbrugge (133-42). In particular, intraperitoneal fluid overload is associated with many diseases and conditions, including intraperitoneal hypertension, abdominal compartment syndrome, and acute renal failure. Volume overload can be addressed through renal replacement therapy. Peters, C.E. 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. 0126882 (hereinafter "Peters"). 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 cardiovascular syndrome, NEJM 2012;367:2296-2304 (hereinafter "Bart"). In light of such problematic effects of fluid retention, systems for improving the removal of fluids such as urine from patients, in particular for increasing the quantity and quality of fluid output from the kidneys and A method is needed.

The present disclosure improves on previous systems by providing specialized catheters for percutaneous insertion and deployment within the patient's renal pelvis and/or kidney.

According to some embodiments, a catheter configured to be deployed in a patient's urinary tract includes a proximal portion configured to pass through the percutaneous opening, a patient's kidney, renal pelvis, and/or a distal portion comprising a retention portion configured to be deployed within the bladder. The retention portion includes one or more protected drainage holes, ports, or perforations, and when deployed, mucosal tissue is forced through the one or more protected drainage holes in response to the application of negative pressure through the catheter. , ports, or perforations to establish an outer perimeter or protective surface area.

According to some other embodiments, a system for inducing negative pressure within a portion of a patient's urinary tract includes a catheter configured to be deployed within a portion of the patient's urinary tract. The catheter includes a proximal portion configured to be passed through the percutaneous opening and a distal portion including a retention portion configured to be deployed within the patient's kidney, renal pelvis, and/or bladder. including. The retention portion includes one or more protected drainage holes, ports, or perforations, and when deployed, mucosal tissue is forced through the one or more protected drainage holes in response to the application of negative pressure through the catheter. , ports, or perforations to establish an outer perimeter or protective surface area. The system also includes a pump external to the patient's body for application of negative pressure at the proximal portion of the catheter. The pump induces a negative pressure in a portion of the urinary tract that causes fluid from the urinary tract to be drawn at least partially through one or more protected drainage holes, ports, or perforations and into the catheter.

According to some other embodiments, a method for removing fluid from a patient's urinary tract comprises inserting a urinary catheter into the patient's kidney, renal pelvis, and/or bladder through a percutaneous opening. and deploying a retention portion of the catheter within the patient's kidney, renal pelvis, and/or bladder to maintain patency of fluid flow from the patient's kidney through at least a portion of the catheter. The catheter includes a proximal portion configured to be passed through the percutaneous opening and a distal portion including a retention portion configured to be deployed within the patient's kidney, renal pelvis, and/or bladder. including. The retention portion includes one or more protected drainage holes, ports, or perforations, and when deployed, mucosal tissue is forced through the one or more protected drainage holes in response to the application of negative pressure through the catheter. , ports, or perforations to establish an outer perimeter or protective surface area.

Non-limiting examples, aspects, or embodiments of the invention will now be described in the following numbered appendices.

Appendix 1: A catheter configured to be deployed in a patient's urinary tract, the proximal portion configured to be passed through a percutaneous opening and the patient's kidneys, renal pelvis, and/or a distal portion comprising a retention portion configured to be deployed within the bladder, the retention portion comprising one or more protected drainage holes, ports or perforations, the catheter configured to establish an outer perimeter or protective surface area that inhibits mucosal tissue from occluding one or more protected vents, ports, or perforations in response to the application of negative pressure through the catheter.

Note 2: The catheter is configured in a deflated configuration that allows the catheter to be passed through the percutaneous opening and the retaining portion retains at least a distal portion of the catheter within the patient's kidney, renal pelvis, and/or bladder. Clause 1. The catheter of Clause 1, wherein the catheter is configured to transition between a deployed configuration.

Clause 3: The catheter of clause 1 or clause 2, wherein when deployed, the maximum outer diameter of the retention portion exceeds the diameter of the catheter's drainage lumen.

Clause 4: When deployed, the retention portion maintains fluid flow patency between the kidney and the proximal end of the catheter such that at least a portion of the fluid flow flows through the expandable retention portion. 4. The catheter of any of Clauses 1-3, comprising an expandable retention portion defining a three-dimensional shape, sized and positioned to.

Note 5: The area of the two-dimensional slice of the three-dimensional shape defined by the expandable retaining portion deployed in a plane transverse to the central axis of the expandable retaining portion is the distal end of the expandable retaining portion. 5. The catheter of paragraph 4, decreasing towards.

Appendix 6: The maximum cross-sectional area of the three-dimensional shape defined by the expandable retaining portion deployed in a plane transverse to the central axis of the expandable retaining portion is less than or equal to about 500 ^mm2 , Appendix 4 or The catheter of paragraph 5.

Clause 7: The retention portion of any clause 1-6, wherein the retention portion comprises a proximal end sized to be positioned within the kidney and a distal end sized to be positioned within the renal pelvis. catheter.

Statement 8: The retaining portion comprises a coiled retaining portion comprising at least a first coil having a first diameter and at least a second coil having a second diameter, the first diameter comprising: A catheter according to any of clauses 1-7, which exceeds the second diameter.

Clause 9: The catheter of Clause 8, wherein the first coil is closer to the proximal portion of the catheter than the second coil.

Appendix 10: The retaining portion comprises a coiled retaining portion comprising a plurality of coils, wherein a distalmost coil of the plurality of coils has a smaller diameter than other coils of the plurality of coils, Appendix 1- 9. A catheter according to any one of 8.

Clause 11: The catheter of Clause 10, wherein the coiled retention portion comprises a straight portion extending through the retention portion, the plurality of coils being wrapped around the straight portion.

Clause 12: The catheter of any of Clauses 1-11, wherein the retention portion is coextensive with other portions of the catheter.

Clause 13: The catheter of any of Clauses 1-12, wherein the axial length of the retention portion from its proximal end to its distal end is from about 5 mm to about 100 mm.

Clause 14: The catheter of any of Clauses 1-13, wherein the one or more protected drainage holes, ports or perforations have diameters ranging from 0.0005 mm to about 2.0 mm.

Clause 15: The catheter of any of Clauses 1-14, wherein the catheter comprises an elongated tube extending from the proximal end of the proximal portion to the distal end of the distal portion.

Clause 16: The catheter of clause 15, wherein the extension tube is about 30 cm to about 60 cm in length.

Clause 17: The catheter of Clause 15 or Clause 16, wherein the extension tube has an outer diameter of about 1.0 mm to about 10.0 mm and/or an inner diameter of about 0.5 mm to about 9.5 mm.

Clause 18: The catheter of any clause 1-17, wherein the proximal end of the proximal portion of the catheter is configured to be connected to a pump for applying negative pressure through the catheter.

Clause 19: A catheter according to any of clauses 1-18, wherein the proximal portion is essentially free or free of perforations and/or drainage ports.

Appendix 20: A system for inducing negative pressure within a portion of a patient's urinary tract, the proximal portion and the patient's kidney, renal pelvis, and/or the patient's kidneys, renal pelvis, and/or system configured to pass through a percutaneous opening. or a catheter configured to be deployed within a portion of a patient's urinary tract comprising a distal portion comprising a retention portion configured to be deployed within the bladder, the retention portion comprising: With one or more protected vents, ports, or perforations, and when deployed, mucosal tissue is exposed to the one or more protected vents, ports, or perforations in response to the application of negative pressure through the catheter. and a pump external to the patient's body for application of negative pressure at a proximal portion of the catheter configured to establish an outer perimeter or protective surface area that prevents occlusion of the The pump induces a negative pressure in a portion of the urinary tract that causes fluid from the urinary tract to be drawn at least partially through one or more protected drainage holes, ports, or perforations into the catheter; system.

Clause 21: The system of Clause 20, further comprising a controller electrically connected to the pump configured to actuate the pump and control the application of negative pressure to the proximal end of the catheter.

Supplement 22: 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, the controller comprising at least one physical 22. The system of clause 21, configured to activate or deactivate operation of the pump based on the parameter.

Clause 23: The system of any of Clauses 20-22, wherein the negative pressure is provided within the range of about 2 mmHg to about 50 mmHg.

Clause 24: The system of any of Clauses 20-23, wherein the pump provides a sensitivity of about 10 mmHg or less.

Appendix 25: A method for removing fluid from a patient's urinary tract comprising inserting a urinary catheter through a percutaneous opening into the patient's kidney, renal pelvis, and/or bladder; , deploying a retention portion of the catheter within the renal pelvis, and/or bladder to maintain patency of fluid flow from the patient's kidney through at least a portion of the catheter, the catheter passing through the percutaneous opening. a proximal portion configured to pass through and a distal portion comprising a retention portion configured to be deployed within a patient's kidney, renal pelvis, and/or bladder, the retention portion comprising: With one or more protected vents, ports, or perforations, when deployed, mucosal tissue opens one or more protected vents, ports, or perforations in response to the application of negative pressure through the catheter. A method configured to establish an outer perimeter or protective surface area that prevents occlusion of the perforation.

Note 26: Inserting a urinary catheter through a percutaneous opening comprises inserting a ureteral catheter needle into a portion of the patient's body to create a percutaneous opening; inserting a needle in and advancing the needle through the kidney to the patient's renal pelvis; and inserting an extension tube of the ureteral catheter over the needle such that the distal end of the extension tube advances from the kidney into the renal pelvis. 26. The method of clause 25, comprising:

Clause 27: The method of Clause 26, wherein inserting the urinary catheter comprises inserting a needle of the urinary catheter into an abdominal region of the patient.

Note 28: By directly or indirectly attaching the proximal end of the urinary catheter to a fluid pump and actuating the pump, a negative pressure is applied to the proximal end of the proximal portion of the urinary catheter, thereby causing the patient's kidneys to 28. The method of any of paragraphs 25-27, further comprising the step of inducing a negative pressure in the pelvis, renal pelvis, and/or bladder.
The present invention provides, for example, the following.
(Item 1)
A catheter configured to be deployed within a patient's urinary tract, said catheter comprising:
a proximal portion configured to pass through the percutaneous opening;
a distal portion comprising a retaining portion configured to be deployed within the patient's kidney, renal pelvis, and/or bladder;
with
The retention portion includes one or more protected vents, ports, or perforations, and upon deployment, the retention portion responds to the application of negative pressure through the catheter to force the mucosal tissue into the one. A catheter configured to establish an outer perimeter or protective surface area that prevents occlusion of one or more protected drainage holes, ports, or perforations.
(Item 2)
The catheter has a retracted configuration that allows the catheter to be passed through the percutaneous opening, and the retention portion retracts at least the distal portion of the catheter within the kidney, renal pelvis, and/or bladder of the patient. The catheter of item 1, configured to transition between a deployed configuration configured to retain.
(Item 3)
The catheter of claim 1, wherein when deployed, the maximum outer diameter of the retention portion is greater than the diameter of the drainage lumen of the catheter.
(Item 4)
The retention portion comprises an expandable retention portion, which, when deployed, allows at least a portion of fluid flow to flow through the expandable retention portion, and to the renal and catheter portions. The catheter of claim 1, defining a three-dimensional shape sized and positioned to maintain patency of said fluid flow between said proximal ends.
(Item 5)
The area of a two-dimensional slice of the three-dimensional shape defined by the deployed expandable retaining portion in a plane transverse to the central axis of the expandable retaining portion is the distal end of the expandable retaining portion. 5. The catheter of item 4, decreasing towards.
(Item 6)
A maximum cross-sectional area of the three-dimensional shape defined by the deployed expandable retaining portion in a plane transverse to the central axis of the expandable retaining portion is less than or ^equal to about 500 ^mm2 , item 4.
(Item 7)
The catheter of claim 1, wherein the retention portion comprises a distal end sized to be positioned within the renal pelvis.
(Item 8)
The retaining portion comprises a coiled retaining portion comprising at least a first coil having a first diameter and at least a second coil having a second diameter, the first diameter The catheter of item 1, greater than the diameter.
(Item 9)
9. The catheter of item 8, wherein the first coil is closer to the proximal portion of the catheter than the second coil.
(Item 10)
2. The method of claim 1, wherein the retaining portion comprises a coiled retaining portion comprising a plurality of coils, a distal most coil of the plurality of coils having a smaller diameter than other coils of the plurality of coils. catheter.
(Item 11)
11. The catheter of claim 10, wherein the coiled retention portion comprises a straight portion extending through the retention portion, and the plurality of coils are wrapped around the straight portion.
(Item 12)
The catheter of item 1, wherein the retention portion is coextensive with other portions of the catheter.
(Item 13)
The catheter of claim 1, wherein the axial length of said retention portion from its proximal end to its distal end is from about 5 mm to about 100 mm.
(Item 14)
The ureteral catheter of item 1, wherein the one or more protected drainage holes, ports, or perforations have diameters ranging from 0.0005 mm to about 2.0 mm.
(Item 15)
The catheter of claim 1, wherein said catheter comprises an elongated tube extending from a proximal end of said proximal portion to a distal end of said distal portion.
(Item 16)
16. The catheter of item 15, wherein the extension tube is about 30 cm to about 120 cm in length.
(Item 17)
16. The catheter of item 15, wherein the extension tube has an outer diameter of about 1.0 mm to about 10.0 mm and/or an inner diameter of about 0.5 mm to about 9.5 mm.
(Item 18)
The catheter of item 1, wherein the proximal end of the proximal portion of the catheter is configured to be connected to a pump for applying the negative pressure through the catheter.
(Item 19)
The catheter of item 1, wherein the proximal portion is essentially free or free of perforations and/or drainage ports.
(Item 20)
A system for inducing negative pressure within a portion of a patient's urinary tract, said system comprising:
a catheter configured to be deployed within a portion of the urinary tract of the patient, the catheter comprising a proximal portion configured to pass through a percutaneous opening; a kidney of the patient; a distal portion comprising a retaining portion configured to be deployed within the renal pelvis and/or bladder, said retaining portion comprising one or more protected vents, ports or perforations, said The retention portion has an outer perimeter that, when deployed, prevents mucosal tissue from occluding the one or more protected vents, ports, or perforations in response to the application of negative pressure through the catheter. a catheter configured to establish a protected surface area;
a pump external to the patient's body for application of the negative pressure at the proximal portion of the catheter;
with
The pump creates a negative pressure in the urinary tract that causes fluid from the urinary tract to be drawn into the catheter at least partially through the one or more protected drainage holes, ports, or perforations. A system that provokes in part.
(Item 21)
21. The method of clause 20, further comprising a controller electrically connected to the pump, the controller configured to operate the pump and control the application of the negative pressure to the proximal end of the catheter. system.
(Item 22)
further comprising one or more physiological sensors associated with the patient, the physiological sensors configured to provide information indicative of at least one physical parameter to the controller, the controller configured to 22. The system of item 21, configured to activate or deactivate operation of the pump based on physical parameters.
(Item 23)
21. The system of item 20, wherein the negative pressure is provided within a range of about 2 mmHg to about 50 mmHg.
(Item 24)
21. The system of item 20, wherein the pump provides an accuracy of about 10 mmHg or less than about 10 mmHg.
(Item 25)
A method for removing fluid from a patient's urinary tract, said method comprising:
inserting a urinary catheter into the patient's kidney, renal pelvis, and/or bladder through a percutaneous opening;
deploying a retention portion of the catheter within the kidney, renal pelvis, and/or bladder of the patient to maintain patency of fluid flow from the kidney of the patient through at least a portion of the catheter;
including
The catheter comprises a proximal portion configured to pass through the percutaneous opening and a retention portion configured to be deployed within the kidney, renal pelvis, and/or bladder of the patient. a distal portion;
The retention portion includes one or more protected vents, ports, or perforations, and upon deployment, the retention portion responds to the application of negative pressure through the catheter to force the mucosal tissue into the one. A method configured to establish an outer perimeter or protective surface area that prevents occlusion of one or more protected vents, ports, or perforations.
(Item 26)
inserting the urinary catheter through the percutaneous opening;
inserting a needle of the ureteral catheter into a portion of the patient's body to create the percutaneous opening;
inserting the needle into the patient's kidney and advancing the needle through the kidney to the patient's renal pelvis;
inserting the elongate tube of the ureteral catheter over the needle such that the distal end of the elongate tube advances from the kidney into the renal pelvis;
26. The method of item 25, comprising
(Item 27)
27. The method of item 26, wherein inserting the urinary catheter comprises inserting the needle of the urinary catheter into an abdominal region of the patient.
(Item 28)
The proximal end of the urinary catheter is directly or indirectly attached to a fluid pump, and a negative pressure is applied to the proximal end of the proximal portion of the urinary catheter by actuating the pump, thereby causing the patient to 26. The method of item 25, further comprising inducing said negative pressure within said kidney, renal pelvis, and/or bladder.

These and other features and characteristics of the present disclosure, as well as the methods of operation and function of the associated elements of construction and the economics of parts and manufacture, all of which form part of the specification, The reference numbers will become more apparent from a consideration of the following description and accompanying appendices, with reference to the accompanying drawings, which designate corresponding parts in the various figures. It is expressly understood, however, that the drawings are for the purpose 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 considered with reference to 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, according to an embodiment of the present invention.

FIG. 1B is a schematic diagram of an indwelling portion of a system comprising ureteral and bladder catheters deployed within a patient's urinary tract, according to an embodiment of the invention.

FIG. 1C is a schematic diagram of an indwelling portion of a system comprising ureteral and bladder catheters deployed in a patient's urinary tract, according to an embodiment of the invention.

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

FIG. 1E is a cross-sectional view of the retaining portion of FIG. 1D taken along line 1E-1E of FIG. 1D, according to an embodiment of the invention.

FIG. 1F is a schematic diagram of an indwelling portion of a system comprising ureteral and bladder catheters deployed within a patient's urinary tract, according to 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 invention;

FIG. 1H is a side elevational view of the retaining portion of FIG. 1G, according to an embodiment of the invention.

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

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

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

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

Figure 1M is a side elevational view of the retaining portion of Figure 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 invention;

FIG. 1O is a cross-sectional view of a portion of the retaining portion of FIG. 1N, according to an embodiment of the invention.

FIG. 1P is a schematic diagram of an indwelling portion of a system comprising ureteral and bladder catheters deployed within a patient's urinary tract, according to 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 invention;

FIG. 1R is a cross-sectional view of a portion of the retaining portion of FIG. 1Q, according to an embodiment of the invention.

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

FIG. 1T is a cross-sectional view of a portion of the retaining portion of FIG. 1S, according to an embodiment of the invention.

FIG. 1U is a schematic diagram of an indwelling portion of a system comprising ureteral and bladder catheters deployed in a patient's urinary tract, according to an embodiment of the invention.

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

FIG. 1W is a cross-sectional view of the retaining portion of FIG. 1V taken along line 1W-1W of FIG. 1V, according to an embodiment of the 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, according to an embodiment of the invention.

FIG. 2B is a schematic diagram of an indwelling portion of a system comprising a ureteral catheter deployed within a patient's urinary tract, according to an embodiment of the invention.

FIG. 3 is a biaxial view of an example of a prior art deformable ureteral stent according to FIG. 1 of PCT Patent Application Publication No. WO2017/019974, the left image showing the uncompressed state of the stent; and the image on the right represents 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. 2002/0183853A1.

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. 2002/0183853A1.

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. 2002/0183853A1.

FIG. 7A is a schematic diagram of another embodiment of an indwelling portion of a system comprising ureteral and bladder catheters deployed within a patient's urinary tract, according to 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 invention.

Figure 7C is a ureter according to the invention positioned within the renal pelvic region of the kidney showing in phantom general changes that may occur within the renal pelvic tissue in response to the application of negative pressure through the ureteral catheter. Fig. 2 is an enlarged schematic view of a portion of the catheter;

FIG. 8A is a perspective view of an exemplary catheter, according to an embodiment of the invention;

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

FIG. 9A is a schematic diagram of an example 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;

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

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

10B is a front view of the retaining portion of FIG. 10A, according to an embodiment of the invention; FIG.

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

FIG. 10D is a top view of the retaining portion of FIG. 10A, according to an embodiment of the invention.

FIG. 10E is a cross-sectional view of the retaining portion of FIG. 10A taken along line 10E-10E, according to an embodiment of the invention.

FIG. 10F is a line according to an embodiment of the invention positioned within the renal pelvic region of the kidney generally showing the changes that are believed to occur within the renal pelvic tissue in response to the application of negative pressure through a ureteral catheter. 10E is a cross-sectional view of the retaining portion of FIG. 10A taken along 10E-10E; FIG.

FIG. 10G shows line 10E-10E according to an embodiment of the invention positioned within the bladder generally showing changes that may occur within bladder tissue in response to the application of negative pressure through a bladder catheter. 10B is a cross-sectional view of the retaining portion of FIG. 10A taken along; FIG.

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 invention;

FIG. 12 is a schematic diagram of another embodiment of a retaining portion of a catheter in a constrained or linear position, according to an embodiment of the present invention;

FIG. 13 is a schematic diagram of another example of a retention portion of a ureteral catheter in a constrained or linear position, according to an embodiment of the present invention;

FIG. 14 is a schematic diagram of another embodiment of a retention portion of a catheter in a constrained or linear position, according to an embodiment of the invention;

FIG. 15A is a graph showing the percentage of fluid flow through an exemplary catheter opening as a function of position, according to 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;

Figure 16 is a schematic diagram of a retention portion of a catheter showing a station for calculating fluid flow coefficients for mass transfer balance assessment, according to an embodiment of the present invention;

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

Figure 18A is a side elevational view of a retention portion of a catheter, according to an embodiment of the invention;

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

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

FIG. 18D is a urine sample according to an embodiment of the present invention positioned within the renal pelvic region of the kidney generally showing the changes that are believed to occur within the renal pelvic tissue in response to the application of negative pressure through the ureteral catheter. Fig. 10 is a cross-sectional view of a retention portion of a vascular catheter;

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

Figure 19 is a side elevational view of a retention portion of another catheter, in accordance with an embodiment of the present invention;

Figure 20 is a side elevational view of a retention portion of another catheter, in accordance with an embodiment of the present invention;

Figure 21 is a side elevational view of a retention portion of another catheter, in accordance with an embodiment of the present invention;

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

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

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

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

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

FIG. 24B is a urine sample according to an embodiment of the present invention positioned within the renal pelvic region of the kidney generally showing changes that may occur within the renal pelvic tissue in response to the application of negative pressure through a ureteral catheter. Fig. 10 is a cross-sectional view of a retention portion of a vascular catheter;

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

Figure 25 is a side elevational view of a retention portion of another catheter, in accordance with an embodiment of the present invention;

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

Figure 27 is a cross-sectional side view of a retention portion of another catheter, in accordance with an embodiment of the present invention;

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

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

FIG. 29A is a perspective view of a retention portion of another catheter, according to an embodiment of the invention;

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

FIG. 29C is a urine sample according to an embodiment of the invention positioned within the renal pelvic region of the kidney generally showing changes that may occur within the renal pelvic tissue in response to the application of negative pressure through a ureteral catheter. Fig. 10 is a cross-sectional view of a retention portion of a vascular catheter;

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

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

Figure 33 is a cross-sectional side elevational view of a retention portion of another catheter, in accordance with an embodiment of the present invention;

Figure 34 is a cross-sectional side elevational view of a retaining portion of another catheter, in accordance with an embodiment of the present invention;

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

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

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

FIG. 37A is a schematic diagram of another example of a retention portion for a catheter, according to an embodiment of the present invention;

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

FIG. 38A is a schematic diagram of another example of a retention portion for a catheter, according to an embodiment of the present invention;

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

FIG. 39A is a schematic diagram of another example of a retention portion for a catheter, according to an embodiment of the present invention;

FIG. 39B is a urine sample according to an embodiment of the present invention positioned within the renal pelvic region of the kidney generally showing the changes believed to occur within the renal pelvic tissue in response to the application of negative pressure through the ureteral catheter. FIG. 10 is a schematic diagram of a cross-sectional view of another embodiment of a retention portion for a vascular catheter;

FIG. 39C for a bladder catheter according to an embodiment of the invention positioned within the bladder generally showing changes that may occur within bladder tissue in response to the application of negative pressure through the bladder catheter. FIG. 10 is a schematic diagram of a cross-sectional view of another embodiment of a retaining portion;

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

FIG. 40B is a urine sample according to an embodiment of the invention positioned within the renal pelvic region of the kidney, generally showing the changes believed to occur within the renal pelvic tissue in response to the application of negative pressure through a ureteral catheter. FIG. 10 is a schematic diagram of a cross-sectional view of another embodiment of a retention portion for a vascular catheter;

FIG. 40C for a bladder catheter according to an embodiment of the invention positioned within the bladder generally showing changes that may occur within bladder tissue in response to the application of negative pressure through the bladder catheter. FIG. 10 is a schematic diagram of a cross-sectional view of another embodiment of a retaining portion;

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

FIG. 41B is a urine sample according to an embodiment of the invention positioned within the renal pelvic region of the kidney generally showing changes that may occur within the renal pelvic tissue in response to the application of negative pressure through a ureteral catheter. FIG. 10 is a schematic diagram of a cross-sectional view of another embodiment of a retention portion for a vascular catheter;

FIG. 41C for a bladder catheter according to an embodiment of the invention positioned within the bladder generally showing changes that may occur within bladder tissue in response to the application of negative pressure through the bladder catheter. FIG. 10 is a schematic diagram of a cross-sectional view of another embodiment of a retaining portion;

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

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

FIG. 43 is a schematic diagram of the renal units and surrounding vasculature showing the location of the capillary bed and convoluted tubules.

Figure 44 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;

45A is a plan view of a pump for use with the system of FIG. 44, according to an embodiment of the invention; FIG.

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

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

FIG. 47 is a graph of creatinine clearance rates for studies performed using the experimental setup shown in FIG.

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

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

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

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

FIG. 49 is a flowchart illustrating a process for reducing creatinine and/or protein levels in a patient, according to embodiments of the invention.

Figure 50 is a flowchart illustrating a process for treating a patient receiving resuscitation infusions, according to an embodiment of the present invention.

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

FIG. 52A is a perspective view of a catheter configured to be inserted into the renal pelvis through a percutaneous access site.

Figure 52B is a side view of the catheter of Figure 52A.

Figure 53 is a cross-sectional view of the catheter of Figure 52A.

FIG. 54 is a schematic diagram showing a ureteral catheter inserted through a percutaneous access site and deployed into the patient's renal pelvis.

FIG. 55 is a schematic diagram of a patient's urinary tract showing a system for collecting fluids, including the ureteral catheter of FIG.

FIG. 56 is a flowchart of a method for deploying a ureteral catheter within the renal pelvis through a percutaneous access site.

57A-57E are schematic diagrams showing steps for inserting a ureteral catheter into a patient's renal pelvis.

FIG. 58A is a perspective view of another example of a catheter configured to be inserted into the renal pelvis through a percutaneous access site, according to aspects of the present disclosure;

Figure 58B is a cross-sectional view of the catheter of Figure 58A.

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

As used herein, the terms "right", "left", "top", and derivatives thereof shall relate to the present invention as oriented in the drawings. The term "proximal" refers to the portion of the catheter device 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 a catheter device configured to be inserted into a patient and/or the portion of the device inserted most distally in the patient's urinary tract. However, it is to be understood that the invention may assume various alternative orientations and thus such terms are not to be regarded as limiting. Also, it is to be understood that the invention is capable of various alternative variations and sequence of steps, unless expressly specified to the contrary. It is also to 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 limiting.

For the purposes of this specification, unless otherwise indicated, all numbers representing quantities of components, reaction states, dimensions, physical properties, etc. used in the specification and claims shall be in all instances referred to by the term " to be understood as being modified by about. Unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending on the desired properties sought to be obtained by the present invention.

Although 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.

Also, it should be understood that any numerical range recited herein is intended to include all sub-ranges subsumed therein. For example, a range of "1 to 10" includes a minimum recited value of 1 and a maximum recited value of 10, and any range therebetween, i.e., starting with the lowest value equal to or greater than 1. , all subranges ending with a maximum value equal to or less than 10 and all subranges in between, such as 1 to 6.3, or 5.5 to 10, or 2.7 to 6.1 intended to include

As used herein, the terms "communicate" and "communicate" refer to the receipt or transfer of one or more signals, messages, commands, or other types of data. Communication of one unit or component with another unit or component means that one unit or component receives, directly or indirectly, data from and/or the other unit or component. It means that data can be transmitted. This may refer to direct or indirect connections, which may be wired and/or wireless in nature. In addition, two units or components are mutually exclusive even if the data transmitted is modified, processed, routed, and the like between the first and second units or components. can communicate to For example, a first unit can 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 can communicate with a second unit while an intermediate unit processes data from one unit and transmits the processed data to the second unit. can. It should be understood that many other arrangements are also possible.

As used herein, "maintaining patency of fluid flow between a patient's kidney and bladder" means from the kidney through the ureter, ureteral stent, and/or ureteral catheter, It means establishing, increasing or maintaining the flow of fluids such as urine out of the bladder as well as the body. In some embodiments, fluid flow is facilitated by providing a protective surface area 1001 within the upper urinary tract and/or bladder and preventing the urinary tract endothelium from contracting or collapsing into the fluid column or flow. or maintained. 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, prior to the application of the negative pressure, to the bladder, respectively. Below the existing pressure at the proximal end of the catheter or the proximal end of the ureteral catheter, respectively, prior to applying the negative pressure, for example, with the proximal end of the bladder catheter or the proximal end of the ureteral catheter, respectively , means that there is a pressure difference between the existing pressure at the proximal end of the bladder catheter or the proximal end of the ureteral catheter. This pressure differential causes fluid from the kidney to be drawn into or through both the ureteral and bladder catheters, respectively, and then out of the patient's body. For example, the negative pressure applied to the proximal end of a bladder catheter or the proximal end of a ureteral catheter is less than atmospheric pressure (about 760 mm Hg or less than about 1 atmosphere) so that fluid is drawn from the kidney and/or bladder; 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. In some examples, the negative pressure applied to the proximal end of the bladder catheter or the proximal end of the ureteral catheter is between about 0.1 mmHg and about 150 mmHg, or between about 0.1 mmHg and about 50 mmHg, or between about 0.1 mmHg and about 50 mmHg. It can range from 1 mmHg to about 10 mmHg, or from about 5 mmHg to about 20 mmHg, or about 45 mmHg (gauge pressure at pump 710 or gauge pressure at negative pressure source). In some embodiments, the negative pressure source comprises a pump external to the patient's body for application of negative pressure through both the bladder and ureteral catheters, which in turn draws fluid from the kidneys. Both the ureteral and bladder catheters are passed through the ureteral catheter and then withdrawn outside the patient's body. In some embodiments, the negative pressure source comprises a vacuum source external to the patient's body for the application and regulation of negative pressure through both the bladder and ureteral catheters, which in turn, from the kidneys. of fluid is drawn into and through both the ureteral and bladder catheters and then out of the patient's body. In some embodiments, the vacuum source is selected from the group consisting of wall suction sources, vacuum bottles, and manual vacuum sources, or the vacuum source is provided by a pressure differential. In some examples, the negative pressure received from the negative pressure source can be controlled manually, automatically, or a combination thereof. In some examples, 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, prior to the application of negative pressure to the bladder, respectively. above the pre-existing pressure at the proximal end of the catheter or the proximal end of the ureteral catheter to force fluid present in or through the ureteral or bladder catheter, respectively, to the bladder or kidney It means to flow toward and back. In some examples, the positive pressure applied to the proximal end of the bladder catheter or the proximal end of the ureteral catheter is between about 0.1 mmHg and about 150 mmHg, or between about 0.1 mmHg and about 50 mmHg, or between about 0.1 mmHg and about 50 mmHg. It can range from 1 mmHg to about 10 mmHg, or from about 5 mmHg to about 20 mmHg, or about 45 mmHg (gauge pressure at pump 710 or positive pressure source). The positive pressure source can be provided by, for example, a pump or wall pressure source, or a pressurized bottle, and can be controlled manually, automatically, or a combination thereof. In some examples, 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 a combination of isotonic volume expansion and secondary compartment syndrome. In some embodiments, the present invention is generally directed to devices and methods for facilitating the evacuation of urine or waste 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 at least a portion of a patient's bladder, ureters, and/or kidneys, eg, the urinary system. Without intending to be bound by any theory, applying negative pressure to at least a portion of the bladder, ureters, and/or kidneys, e.g., the urinary system, may, in some circumstances, reduce sodium and medullary renal unit tubular reabsorption of water. Compensation for sodium and water reabsorption can increase urine production, decrease total body sodium, and improve red blood cell production. Since intramedullary pressure is driven by sodium and thus by volume overload, targeted removal of excess sodium allows maintenance of volume loss. Removal of fluid volume restores medullary stasis. 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 development 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 relieving or reducing venous congestion. In addition, treatment and/or inhibition of AKI is expected to positively affect and/or reduce the incidence of other conditions, such as NYHA grade III and/or grade IV heart failure. Reducing or preventing deterioration of renal function in the patient.異なるレベルの心不全の分類は、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 can also be a treatment for stage 4 and/or 5 chronic kidney disease. Chronic kidney disease progression is reviewed in the National Kidney Foundation, K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am. J. Kidney Dis. 39:S1-S266, 2002 (Suppl. 1), the disclosure of which is incorporated herein by reference in its entirety.

Ureteral catheters, ureteral stents, and/or bladder catheters disclosed herein are also useful for preventing, delaying the onset of, and/or treating end-stage renal disease (“ESRD”) can be The average dialysis patient spends about $90,000 a year in medical use for a total US government cost of $33.9 billion. Currently, ESRD patients comprise only 2.9% of all Medicare beneficiaries, but account for over 13% of total spending. Although the incidence and cost per patient have stabilized in recent years, the volume of active patients continues to rise.

The 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 capture improves with increasing symptoms and disease severity.

The CKD3b/4 subgroup is a smaller subgroup that reflects important changes in disease progression, healthcare system involvement, and transition to ESRD. Emergency department visits rise with the severity of CKD. Within the US VA population, nearly 86% of concomitant dialysis patients had been hospitalized within the five years preceding admission. Of those, 63% were hospitalized at the start of dialysis. This suggests a very large opportunity to intervene prior to dialysis.

Despite traveling further down the arterial tree than other organs, the kidney receives a disproportionate amount of cardiac output at rest. The glomerular membrane represents the path of least resistance for filtrate into the tubules. In a healthy state, renal units have multiple complex and redundant means of self-regulation within the normal range of arterial pressure.

Venous congestion is associated with decreased renal function and is associated with systemic hypervolemia found in late-stage CKD. Because the kidney is covered with a semi-rigid capsule, small changes in venous pressure translate into direct changes in intratubular pressure. This shift in intratubular pressure has been shown to upregulate sodium and water reabsorption, perpetuating a vicious circle.

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

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

It is important to note that the tissue of the urinary tract is lined with urothelium, a type of transitional epithelium. The tissue lining inside the urinary tract is also referred to as uroendothelium or urothelial tissue, such as the mucosal tissue 1003 of the ureter and/or kidney and bladder tissue 1004 . The urothelium is extremely elastic, allowing a significant range of crushability and stretchability. The urothelium, which lines the ureteral lumen, is initially surrounded by the lamina propria, a thin layer of loose connective tissue, both of which consist of 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 to a collapsed stellate cross-section and then expand to full distension during diuresis. Histology of any normal ureter cross-section reveals this stellate lumen in humans and other mammals, which is generally used in translational medicine research. Wolf et al. , "Comparative Uteral Microanatomy", JEU 10: 527-31 (1996).

The process of transporting urine from the kidney to the bladder is facilitated by contractions through the renal pelvis and peristalsis distally through the rest of the ureter. The renal pelvis is the expansion of the proximal ureter into a funnel shape where the ureter enters the kidney. It has been shown that the renal pelvis is actually a continuation of the ureter, consisting of the same tissue, but with one additional muscle layer that allows it to contract. Dixon and Gosling, "The Muscle of the Human Renal Calyces, Pelvis and Upper Urter," J. Am. Anat. 135: 129-37 (1982). These contractions push urine through the renal pelvic infundibulum, allowing peristaltic waves to propagate fluid through the ureters to the bladder.

Imaging studies have shown that a dog's ureter can readily 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). Among the pigs, which are considered the closest animal model for the human upper urinary tract, the renal pelvis and most proximal ureter have indeed been shown to be the most flexible of all ureteral segments. Gregersen, et al. , "Regional Differences Exist in Elastic Wall Properties in the Urter", SJUN 30: 343-8 (1996). Wolf's comparative studies of various study animals with the human ureteral microanatomy showed comparable thicknesses of the lamina propria to the total ureteral diameter in dogs (29.5% in humans and 34% in dogs), and A comparable proportion of smooth muscle to total muscle cross-sectional area in pigs (54% in humans and 45% in pigs) was demonstrated. Although there are certainly limits to comparisons between species, dogs and pigs have become strong focal points in studying and understanding human ureteral anatomy and physiology, and their reference values are highly valuable. Support level translatability.

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

While not intending to be bound by any theory, the inventors believe that the application of negative pressure may help promote fluid flow out of the kidney, allowing the surrounding tissues to enter the fluid column under negative pressure. Application of negative pressure within the renal pelvis is a very specific tool designed to deploy a protective surface area to open or maintain the interior of the renal pelvis open while preventing it from contracting or collapsing. theorized that it is needed to promote The inventive catheter designs disclosed herein provide a protective surface area to prevent surrounding urothelial tissue from contracting or collapsing into a fluid column under negative pressure. The inventive catheter design disclosed herein can normally maintain a stellate longitudinal fold of the ureteral wall away from the central axis of the catheter drainage lumen and the protected orifice, allowing peristaltic waves to It is believed that natural sliding and/or downward movement of the catheter following the stellate cross-sectional area of the ureteral lumen can be prevented.

Also, the inventive catheter design disclosed herein can avoid an unprotected open hole at the distal end of the drainage lumen, which cannot protect the surrounding tissue during aspiration. Although it is convenient to think of the ureter as a straight tube, the true ureter and renal pelvis may enter the kidney at different angles. Lippincott Williams & Wilkins, Annals of Surgery, 58, Figs 3 & 9 (1913). Therefore, it may 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 has no means of ensuring any positive or consistent distance from the tissue wall, thereby allowing tissue to occlude the unprotected open hole. and may present a local suction point at risk of tissue damage. Also, the inventive catheter design disclosed herein leaves an unprotected open hole at the distal end of the drainage lumen near the kidney that can result in aspiration and/or occlusion of the renal calyx. , balloon placement can be avoided. Placement of a balloon with an unprotected open hole at the distal end of the drainage lumen at the base of the ureteral-pelvic junction can result in suction and obstruction by the renal pelvic tissue. Also, a rounded balloon may present a risk of ureteral avulsion or other injury from additional traction on the balloon.

Delivering negative pressure into a patient's renal area presents several anatomical challenges for at least three reasons. First, the urinary system consists of highly flexible tissue that is easily deformed. Medical texts often describe the bladder as a thick muscular structure that can remain in a fixed shape regardless of the volume of urine it contains. In reality, however, the bladder is a soft deformable structure. The bladder contracts and conforms to the volume of urine contained within it. An empty bladder resembles a deflated latex balloon more than a ball. In addition, the inner mucosal lining of the bladder is soft and susceptible to inflammation and injury. It is desirable to avoid drawing urinary tissue into the orifice of the catheter, maintain proper fluid flow therethrough, and avoid injury to 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 activity and pressure gradients within the open system. In peristaltic activity, the urinary portion is pushed ahead of the contractile wave, which almost completely occludes the lumen. The wave pattern starts within the renal pelvis area, propagates along the ureters, and terminates at the bladder. Such a complete occlusion can interrupt fluid flow and prevent negative pressure delivered within the bladder from reaching the renal pelvis unaided. A second type of transport, by a pressure gradient through the wide-open ureter, may exist during the bulk urine flow. During such cycles of voluminous urine production, pressure heads within the renal pelvis may not necessarily be caused by contraction of the smooth muscle of the upper urinary tract, but rather are generated by the forward flow of urine, thus Reflects arterial blood pressure. Kiil F. , "Urinary Flow and Ureteral 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 wall of the renal pelvis can dilate to accommodate the normal volume multiple times, as occurs, for example, in patients with hydronephrosis.

More recently, the use of negative pressure within the renal pelvis to remove a thrombus from the renal pelvis by use of suction has been warned 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. p92. Springer (2016).

Without intending to be bound by any theory, it is believed that the tissues of the renal pelvis and bladder are sufficiently flexible to be drawn inward during delivery of negative pressure. conforms to the shape and volume of the tool being used to Similar to the vacuum seal of a shelled corn ear, the urothelial tissue will collapse around and conform to the negative pressure source. To prevent tissue from occluding the lumen and impeding urine flow, we determined that sufficient protective surface area to maintain the fluid column when a slight negative pressure is applied is occluded. theorized that it would prevent or deter

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

Since the renal pelvis consists of longitudinally oriented smooth muscle cells, a protective surface area would ideally incorporate a multi-planar approach to establishing a protected surface area. Anatomy is often organized in three planes: sagittal (vertical anterior-posterior dividing the body into right and left parts), coronal (vertical left-right dividing the body into dorsal and abdominal parts), and transverse. Described in terms of planes (horizontal or axial, which divides the body into superior and inferior and is perpendicular to the sagittal and coronal planes). Smooth muscle cells within the renal pelvis are oriented vertically. It is desirable that the catheter also maintain radial surface area across many cross-sections between the kidney and ureter. This allows the catheter to occupy both the longitudinal and horizontal portions of the renal pelvis in establishing a protective surface area 1001. Additionally, given the flexibility of tissues, protection of these tissues from the 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. be. When deployed, the deployable/retractable mechanism supports the urothelium and prevents urothelial tissue from occluding openings in the catheter during application of negative pressure through the catheter lumen. to create a protective surface area 1001 within the renal pelvis. In some examples, 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 indicated at 1 comprises right kidney 2 and left kidney 4 of a patient. As discussed above, the kidneys 2, 4 are involved in hemofiltration and clearance of waste compounds from the body through urine. Urine produced by the right kidney 2 and the left kidney 4 is discharged through the renal tubules, namely 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 ureter walls as well as by gravity. The ureters 6 , 8 enter the bladder 10 through the ureteral orifice or orifice 16 . Bladder 10 is a flexible, 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 bladder top wall 70 is, for example, as mesh 57 in FIGS. 1A and 1B, as coil 1210 in FIGS. 1C, 1U, and 7A, and as a basket of bladder top wall support 210 in FIG. 1F. Positioned adjacent the outer perimeter 72, 1002 or protective surface area 1001 of the distal end 136 of the bladder catheter 56, 116, shown as a shaped structure or support cap 212, as an annular balloon 310 in FIG. 1P, and as a funnel 116 in FIG. and/or can be conformal thereto. Normally, when bladder 10 reaches a substantially full condition, urine is allowed to drain from bladder 10 into urethra 12 through urethral sphincter or opening 18 located in the lower portion of bladder 10 . Contraction of bladder 10 may respond to stresses and pressures applied to triangular region 14 of bladder 10 , which is the triangular region extending between ureteral orifices 16 and urethral orifices 18 . Trigone region 14 is sensitive to stress and pressure such that pressure on trigone region 14 increases as bladder 10 begins to fill. Upon exceeding a threshold pressure on trigone region 14 , bladder 10 begins to contract and expel collected urine through urethra 12 .

Similarly, as shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, and 2B, for example, the outer perimeter 72, 1002 or protective surface area 1001 of the ureteral catheters 112, 114 of the present invention may The ducts and/or renal tissue 1003 can be supported to maintain patency of fluid flow between the patient's kidneys and bladder.

In some embodiments, methods and systems 50, 100, for example, as shown in FIGS. etc.) and the method is provided for removing ureteral stents 52, 54 (shown in FIG. 1A) or ureteral catheters 112, 114 (FIGS. 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7, 17 and 44) into the patient's ureters 6, 8 to maintain patency of fluid flow between the patient's kidneys 2, 4 and the bladder 10; and/ or deploying the bladder catheter 56, 116 into the patient's bladder 10, the bladder catheter 56, 116 having a distal end 136 configured to be positioned within the patient's bladder 10 and a proximal end 136 configured to be positioned within the patient's bladder 10; 117 and sidewalls 119 extending therebetween, and negative pressure is applied to the proximal ends 117 of the bladder catheters 56, 116 and/or the ureteral catheters 112, 114. and inducing a negative pressure within a portion of the patient's urinary tract to 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, wherein FIGS. 1P, 1U, 2A, 2B, 7, 17, and 44, including maintaining patency of fluid flow between the patient's second kidney and the bladder. Specific characteristics of exemplary ureteral stents or ureteral catheters of the invention are described in detail below.

In some non-limiting examples, the ureteral or bladder catheter 56, 112, 114, 116, 312, 412, 512, 812, 1212, 5000, 5001 includes (a) a proximal portion 117, 128, 1228; 5006, 5007, 5017; and (b) a distal portion 118, 318, 1218, 5004, 5005, the distal portion including one or more protected vents, ports, or perforations 133, 533, 1233; and in response to the application of negative pressure through the catheter, urothelial tissue, such as mucosal tissue 1003 of the ureters and/or kidneys and bladder tissue 1004, opens one or more protected drainage holes, ports, or a retaining portion 130, 330, 410, 500, 1230, 1330, 2230, 3230, 4230 configured to establish an outer perimeter 1002 or protective surface area 1001 that prevents occlusion of the perforations 133, 533, 1233; 5012 and 5013 are provided.

Exemplary Ureteral Catheter:
As shown in FIGS. 2A, 7, 17, and 44, an embodiment of system 100 is illustrated that includes ureteral catheters 112, 114 configured to be positioned within a patient's urinary tract. For example, the distal ends 120, 121, 1220, 5019, 5021 of the ureteral catheters 112, 114 may be placed in the patient's ureter 2, 4, the renal pelvis 20, 21 area of the kidney 6, 8, or one of the kidneys 6, 8. It can be configured to be deployed in at least one.

In some examples, suitable ureteral catheters are disclosed in U.S. Pat. 15/687,083, each of which is incorporated herein by reference.

In some embodiments, the system 100 includes a first catheter 112 positioned within or adjacent to the renal pelvis 20 of the right kidney 2 and a second catheter 112 positioned within or adjacent to the renal pelvis 21 of the left kidney 4 . There may be two separate ureteral catheters, such as the catheter 114 of . Catheters 112, 114 can be separate for their entire length, or held in close proximity to each other by clips, rings, clamps, or other types of connection mechanisms (eg, connectors), and catheters 112, 114 can facilitate the placement or removal of 2A, 7, 17, 27, and 44, the proximal end 113, 115 of each catheter 112, 114 is positioned within or within the bladder 10 to drain fluid or urine into the bladder. located at the proximal end of the ureter near the . In some examples, 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, catheters 112 , 114 can be fused or connected together within the bladder to form a single drainage lumen that drains into bladder 10 .

As shown in FIG. 2A, in some embodiments, the proximal ends 113, 115 of one or both of the catheters 112, 114 are positioned within the urethra 12 to optionally direct fluid outside the patient's body. Can be connected to additional drain tubing for draining. 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 outside the patient's body. can.

In other embodiments, the catheters 112, 114 are inserted through or enclosed within another catheter, tube, or sheath along a portion or section thereof to facilitate insertion of the catheters 112, 114 into the patient's body. and can facilitate retreat from it. 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. can be

1B, 1C, 1F, 1P, 1U, 2A, 2B, 7, 8A, and 8B, an exemplary ureteral catheter 112, 1212, 5000 includes at least one elongated body or tube 122, 1222, 5009. The interior of which defines or comprises one or more drainage channels or lumens, such as drainage lumens 124 , 1224 , 5002 . Tubing 122, 1222, 5009 sizes can range from about 1 Fr to about 9 Fr (French catheter scale). In some examples, 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, tube 122 is 6 Fr and has an outer diameter of 2.0±0.1 mm. The length of tube 122, 1222, 5009 can range from about 30 cm to about 120 cm, depending on the patient's age (eg, child or adult) and gender.

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

At least some or all of the interior or exterior of catheter 112, 1212, 5000, e.g., tube 122, 1222, 5009, may be hydrophilic to facilitate insertion and/or removal and/or to improve comfort. can be coated with a protective coating. In some examples, the coating is a hydrophobic and/or lubricious coating. For example, suitable coatings are Koninklijke DSM N.T. V. ComfortCoat® hydrophilic coating, available from Co., Ltd., or a hydrophilic coating consisting of a polyelectrolyte as disclosed in U.S. Pat. No. 8,512,795, which is incorporated herein by reference. can be provided.

In some embodiments, for example, as shown in FIG. 8B, the tube 122 has a distal portion 118 (eg, a portion of the tube 122 configured to be positioned within the ureters 6, 8 and the renal pelvis 20, 21). portion), a central portion 126 (eg, a portion of tube 122 configured to extend from distal portion 118 through ureteral opening 16 and into patient's bladder 10 and urethra 12), and proximal portion 128 (eg, the portion of tube 122 that extends into bladder 10 or urethra 12, or extends from urethra 12 outside the patient's body). In one embodiment, the combined length of proximal portion 128 and central portion 126 of tube 122 is approximately 54±2 cm. In some embodiments, tube 122 terminates within bladder 11 . Fluid is then drained from the proximal ends of the ureteral catheters 112, 114 and directed from the body through additional indwelling bladder catheters. In other embodiments, tube 122 terminates within urethra 12, eg, a bladder catheter is not required. In other embodiments, the tube extends from the urethra 12 outside the patient's body, eg, no bladder catheter is required.

Exemplary Ureteral Retaining Portion:
Any of the retention portions disclosed herein can be formed from the same material 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 and connected to a different material such as those discussed above with respect to the drainage lumen. For example, the retention portion may be made of the aforementioned materials such as polyurethane, flexible polyvinyl chloride, polytetrafluoroethylene (PTFE), 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).

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

In some embodiments, retention portion 130 is integral with tube 122 . Retaining portion 130 may then be formed by imparting a bend or inflection to catheter body 122 that is sized and shaped to retain the catheter at the desired fluid collection location. Suitable bends or coils may include pigtail coils, corkscrew coils, and/or helical coils as shown in FIGS. 1, 2A, 7A, and 8A-10G. For example, the retention portion 130 brings the catheter 112 in the ureters 6, 8 into contact proximate to or within the renal pelvis 20, 21, eg, as shown in FIGS. 2A, 7A, and 8A-10G; One or more radially and longitudinally extending helical coils configured for passive retention may be provided. In other embodiments, retention portion 130 is formed from a radially flared or tapered portion of catheter body 122 . For example, the retention portion 130 can further comprise a fluid collecting portion such as a tapered or funnel-shaped inner surface 186 as shown in FIGS. 17-41C. In other embodiments, retention portion 130 can comprise a separate element connected to and extending from catheter body or tube 122 .

In some embodiments, the retaining portion 130 further includes vent holes, perforations, or ports 132, 1232 (eg, FIGS. 9A-9E, 10A, 10E, 11-14, 27, 32A, 32B, 33, 34, and 39-41A-C)). Evacuation ports 132 can be located at open distal ends 120, 121 of tube 122, for example, as shown in FIG. 10D. In other embodiments, perforated sections and/or exhaust ports 132, 1232 are configured as shown in FIGS. , along the side wall 109 of the distal portion 118 of the catheter tube 122 or within the material of the retention portion, such as the sponge material of FIGS. Drainage ports or holes 132, 1232 can be used to aid in fluid collection, thereby allowing fluid to flow into the drainage lumen for removal from the patient's body. In other embodiments, retention portion 130 is dedicated to storage structures and fluid collection and/or application of negative pressure is provided by structures elsewhere on catheter tube 122 .

In some embodiments, such as shown in FIGS. 9B-E, 10D-G, 18B, 18C-E, 20, 22A-35, 37B, 38A, 39B, 40A-41C, vents, ports, or perforations 132 , 1232 does not allow tissue 1004, 1003 from the bladder or kidney to directly contact or partially or completely occlude protected vents, ports, or perforations 133. positioned within the ureteral catheter 112, 114 or bladder catheter 116 within the protected surface area or inner surface area 1000 to prevent it from For example, as shown in FIGS. 2A-2C, 7A, 7B, 10F, 17, 18D, 24B, 29C, 39B, 40B, and 41B, when negative pressure is induced in the ureter and/or renal pelvis, A portion of the ureter and/or renal mucosal tissue 1003 can be pulled against the outer perimeter 72, 1002 or protective surface area 1001 or outer region of the retaining portion 130, and the outer perimeter 72, 1002 or protective surface area of the retaining portion 130. A number of vents, ports, or perforations 134 located on 1001 may be partially or completely occluded. Similarly, when negative pressure is induced in the bladder, as shown in FIGS. A portion of bladder tissue 1004, such as lamellar connective tissue, lamina propria, and/or fatty connective tissue, may be pulled against the outer perimeter 72, 1002 or protective surface area 1001 or outer region of the retaining portion 130, and the retaining portion A number of vent holes, ports, or perforations 134 located on the outer perimeter 1002 or protected surface area 1001 or outer region of 130 may be partially or completely occluded.

At least a portion of the protected exhaust port 133 located on the protected surface area or the inner surface area 1000 of the retaining portion 130 is such that such tissue 1003, 1004 is outside perimeter 72, 1002 of the retaining portion 130 or the protected surface area 1001 or It will not be partially or completely occluded when contacting the outer region. Additionally, the risk of injury to tissue 1003, 1004 from pinching or contact with the evacuation port 133 can be reduced or ameliorated. The configuration of the outer perimeter 72 , 1002 or protective surface area 1001 or outer region of the retaining portion 130 depends on the overall configuration of the retaining portion 130 . Generally, the outer perimeter 72 , 1002 or protective surface area 1001 or outer region of the retaining portion 130 contacts and supports the bladder 1004 or kidney tissue 1003 thereby providing protection for the protected drainage hole, port, or perforation 133 . Prevent blockage or obstruction.

For example, as shown in FIGS. 10E-G, an exemplary retaining portion 1230 comprising a plurality of helical coils 1280, 1282, 1284 is shown. The outer perimeter 1002 or protected surface area 1001 or outer region of the helical coils 1280, 1282, 1284 contacts and supports bladder tissue 1004 or kidney tissue 1003, and the protected surface areas or inner regions of the helical coils 1280, 1282, 1284 Prevents blockage or obstruction of protected vents, ports, or perforations 1233 located within surface area 1000 . The outer perimeter 1002 or protected surface area 1001 or outer region of the helical coils 1280 , 1282 , 1284 provide protection for protected vents, ports, or perforations 1233 . In FIG. 10F, kidney tissue 1003 is shown surrounding and contacting at least a portion of the outer perimeter 1002 or protective surface area 1001 or outer region of helical coils 1280, 1282, 1284, which is in contact with helical coils 1280, 1282. , 1284 from contacting the renal tissue 1003 with the protected or inner surface area 1000, thereby preventing partial or complete obstruction of the protected vent, port, or perforation 1233 by renal tissue 1003. In FIG. 10G, bladder tissue 1004 is shown surrounding and contacting at least a portion of the outer perimeter 1002 or protective surface area 1001 or outer region of helical coils 1280, 1282, 1284, which is in contact with helical coils 1280, 1282. , 1284 from contacting the protected or inner surface area 1000 of the bladder tissue 1004, thereby preventing partial or complete obstruction of the protected drainage hole, port, or perforation 1233 by the bladder tissue 1004.

Similarly, FIGS. Other examples of bladder and/or ureter retention portion configurations are also shown at 31, 32A, 32B, 33, 34, 35A, 35B, 36, 37A, 37B, 38A, 38B, 39, 40, and 41. , to contact and support bladder tissue 1004 or kidney tissue 1003 and to block or block protected drainage holes, ports, or perforations 133, 1233 located within the protected or inner surface area 1000 of the retaining portion. provides an outer perimeter 1002 or protective surface area 1001 or outer region that may inhibit Each of these examples will be discussed further below.

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

The retention portion 130 further comprises one or more drainage holes 132, 1232 (eg, shown in FIGS. 9A-9E, 10A, and 10E) configured to draw fluid into the interior of the catheter tube 122. be able to. In some embodiments, the retention portion 130 includes 2, 3, 4, 5, 6, 7, 8 or more discharge holes 132 , 1232 plus additional holes 110 . A distal tip or end 120 of the retention portion may be provided. In some embodiments, the diameter of each of the discharge holes 132, 1232 (eg, shown in FIGS. 9A-9E, 10A, and 10E) can range from about 0.7 mm to 0.9 mm, preferably , about 0.83±0.01 mm. In some embodiments, additional holes 110 (eg, shown in FIGS. 9A-9E, 10A, and 10E) at the distal tip or end of retaining portion 130 have a diameter of about 0.165 mm to about 2.39 mm. , or from about 0.7 to about 0.97 mm. The distance between adjacent discharge holes 132, specifically the linear distance between the nearest outer edges of the discharge holes 132, 1232 when the coil is straightened, is about 15 mm ± 2.5 mm, or about 22.5 mm ± 2.5 mm or more.

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

In some examples, 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 may range from about 10 mm to about 30 mm. A height H2 between each adjacent coil 184 may range from about 3 mm to about 10 mm.

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

In some examples, the outer diameter D1 of the coils 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 be increased or decreased by a regular amount (eg, between about 10% and about 25% between adjacent coils 184). For example, for a retention portion 130 having three coils (eg, as shown in FIGS. 9A and 9B), the outer diameter D2 of the proximal-most or first coil 183 can be between about 6 mm and 18 mm; The outer diameter D3 of the central or second coil 185 can be from about 8 mm to about 24 mm, and the outer diameter D13 of the distal-most or third coil 187 can be from about 10 mm to about 30 mm. .

Retention portion 130 further includes an evacuation perforation, hole, or port 132 disposed on or adjacent to retention portion 130 and on or through side wall 109 of catheter tube 122 to allow urine waste to exit catheter tube 122 . from the outside of the catheter tube 122 to the inner drainage lumen 124 of the catheter tube 122 . The location and size of exhaust port 132 can vary depending on the desired flow rate and configuration of retaining portion 130 . Diameter D11 of each of exhaust ports 132 can independently range from about 0.005 mm to about 1.0 mm. The spacing D12 between the nearest edges of each of the exhaust ports 132 can independently range from about 1.5 mm to about 5 mm. Evacuation ports 132 can be spaced in any arrangement, such as a random, linear, or offset arrangement. In some examples, the exhaust port 132 can be non-circular and have a surface area of about 0.00002-0.79 mm ² .

In some embodiments, drainage ports 132 are located around the outer perimeter 72, 1002 or the entire protective surface area 1001 of the side wall 109 of the catheter tube 122 and within the drainage lumen 124, as shown in FIG. 9A. Increase the amount of fluid that can be withdrawn (shown in Figures 2, 9A, and 9B). In other embodiments, as shown in FIGS. 9B-9E and 10-10E, the exhaust holes, ports, or perforations 132 are essentially the protected or inner surface area 1000 of the coil 184 or radially inward. The outwardly facing side 1288 of the coil can be positioned only or only on the facing side 1286 to prevent blockage or blockage of the exhaust ports 132,1232, the outwardly facing side 1288 of the coil being essentially the exhaust port 132,1232. , or the exhaust port 132, 1232 may be absent. The outer perimeters 72, 189, 1002 or protective surface areas 1001 or outer regions 192 of the helical coils 183, 184, 1280, 1282, 1284 contact and support bladder tissue 1004 or kidney tissue 1003, and the helical coils 183, 184 , 1280, 1282, 1284 located within the protected or inner surface area 1000 of the protected vents, ports, or perforations 133, 1233 can be prevented from blocking or blocking. For example, when negative pressure is induced in the ureter and/or renal pelvis, the mucosal tissue of the ureter and/or kidney can be drawn against the retaining portion 130, causing the outer perimeter 72, 189, 1002 of the retaining portion 130 to expand. Some of the upper exhaust ports 134 may be blocked. Exhaust ports 133, 1233 located on the radially inward side 1286 of the storage structure or on the protected or inner surface area 1000 allow such tissue 1003, 1004 to reach the outer perimeter 72, 189, 1002 of the retention portion 130 or protected. When contacting the surface area 1001 or the outer region, it will not be significantly occluded. Additionally, the risk of injury to tissue from pinching or contact with the evacuation ports 132, 133, 1233 or protected evacuation holes, ports or perforations 133, 1233 can be reduced or ameliorated.

9C and 9D, another embodiment of ureteral catheter 112 having retention portion 130 comprising multiple coils 184 is illustrated. The retaining portion 130 comprises three coils 184 extending about axis A, as shown in FIG. 9C. Axis A is an arc of curvature and extends from a central longitudinal axis L of a portion of proximal drainage lumen 181 of retention portion 130 . The curvature imparted to the retaining portion 130 can be selected to correspond to the curvature of the renal pelvis, which comprises a conical container-shaped cavity.

In another exemplary embodiment, the retaining portion 130 can comprise two coils 184 extending about an angled axis A, as shown in FIG. 9D. Angled axis A extends at an angle from central longitudinal axis L and is angled with respect to an axis generally perpendicular to central axis L of the portion of the discharge lumen, as indicated by angle β. Angle β can range from about 15 to about 75 degrees (eg, from about 105 to about 165 degrees relative to the central longitudinal axis L of the drainage lumen portion of catheter 112).

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

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

In some examples, the retaining portion comprises a plurality of radially extending coils 184 . Coil 184 is configured in the shape of a funnel, thereby forming a funnel-shaped support. Some examples of coiled funnel supports are shown in FIGS. 2A-C, 7A, 7B, 8A, and 8A-10E.

In some embodiments, 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 is less than the second diameter and the maximum distance between a portion of the side wall of the first coil and an adjacent portion of the side wall of the second coil is between about 0 mm and about 10 mm. reach. In some embodiments, the first diameter of first coil 183 ranges from about 1 mm to about 10 mm and the second diameter of second coil 184 ranges from about 5 mm to about 25 mm. In some examples, the diameter of the coil increases toward the distal end of the drainage lumen, resulting in a helical structure having a tapered or partially tapered configuration. In some embodiments, second coil 184 is closer to the end of distal portion 118 of drainage lumen 124 than first coil 183 . In some embodiments, second coil 184 is closer to the end of proximal portion 128 of drainage lumen 124 than 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. The facing side 1286 comprises at least one opening 133, 1233 to allow fluid flow into the drainage lumen and the outwardly facing side 1288 is essentially free of openings, or Absent. In some examples, at least one opening 133, 1233 has an area ranging from about 0.002 mm ² to about 100 mm ² .

In some examples, the first coil 1280 comprises a sidewall 119 comprising a radially inwardly facing side 1286 and a radially outwardly facing side 1288, with the radius of the first coil 1280 Directionally inwardly facing side 1286 includes at least one opening 1233 to allow fluid flow into the drainage lumen.

In some examples, the first coil 1280 comprises a sidewall 119 comprising a radially inwardly facing side 1286 and a radially outwardly facing side 1288, with the radius of the first coil 1280 Directionally inwardly facing side 1286 includes at least two openings 1233 to allow fluid flow into drainage lumen 1224 .

In some examples, the first coil 1280 comprises a sidewall 119 comprising a radially inwardly facing side 1286 and a radially outwardly facing side 1288, with the radius of the first coil 1280 Directionally outwardly facing side 1288 is essentially free or void of one or more openings 1232 .

In some examples, the first coil 1280 comprises a sidewall 119 comprising a radially inwardly facing side 1286 and a radially outwardly facing side 1288, with the radius of the first coil 1280 Directionally inwardly facing side 1286 includes at least one opening 1233 to allow fluid flow into exhaust lumen 1224, and radially outwardly facing side 1288 includes one or more The opening 1232 is essentially absent or absent.

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

In some examples, retention portion 1230 includes perforations, exit ports, or openings 1232 in sidewalls of tube 1222 . As described herein, the location and size of openings 1232 may vary depending on the desired volumetric flow rate for each opening and size constraints of retaining 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 from about 0.002 mm ² to about 5 mm ² . Openings 1232 can be positioned to extend along sidewall 119 of tube 1222 in any direction desired, such as longitudinally and/or axially. In some examples, the spacing between nearest adjacent edges of each of openings 1232 can range from about 1.5 mm to about 15 mm. Fluid passes into drain lumen 1234 through one or more of perforations, drain ports, or openings 1232 . Desirably, openings 1232 are positioned such that they are not occluded by tissue of ureter 6, 8 or kidney 1003 when negative pressure is applied to drain lumen 1224. FIG. For example, as described herein, openings 1233 may be positioned over internal portions or protected surface areas 1000 of coils or other structures of retaining portion 1230 to avoid occlusion of openings 1232, 1233. can do. In some embodiments, central portion 1226 and proximal portion 1228 of tube 1222 are essentially free or free of perforations, ports, openings, or openings, such as openings along those portions of tube 1222 . Occlusion can be avoided. In some examples, portions 1226 , 1228 that are essentially free of perforations or openings include substantially fewer openings 1232 than other portions, such as distal portion 1218 of tube 1222 . For example, the total area of openings 1232 in distal portion 1218 may exceed or substantially exceed the total area of openings in central portion 1226 and/or proximal portion 1228 of tube 1222 .

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

In many embodiments, openings 1232 are generally circular in shape, although triangular, elliptical, square, diamond-shaped, and any other opening shapes may also be used. Further, as will be appreciated by those skilled in the art, the shape of opening 1232 may change as tube 1222 transitions between an uncoiled or extended position and a coiled or deployed position. The shape of the opening 1232 may vary (eg, the orifice may be circular in some locations and slightly elongated in others), but the area of the opening 1232 may be expanded or expanded. Note the substantial similarity in the extended or uncoiled position compared to the coiled position.

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

As shown in FIGS. 7A and 10-14, the exemplary ureteral catheter 1212 comprises at least one elongated body or tube 1222 within which one or more drainage channels or lumens, such as drainage lumen 1224. define or comprise Tubing 1222 sizes can range from about 1 Fr to about 9 Fr (French catheter scale). In some examples, 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, tube 1222 is 6Fr and has an outside or outer diameter of 2.0±0.1 mm. The total length of tube 1222 can range from about 30 cm to about 120 cm, depending on the patient's age (eg, child or adult) and gender.

Tube 1222 is made of a flexible material, such as any of the materials discussed above, to facilitate advancement and/or positioning of tube 1222 within bladder 10 and ureters 6, 8 (shown in FIG. 7). and/or can be formed from a deformable material. For example, tube 1222 can be formed from one or more materials such as biocompatible polymers, polyvinyl chloride, polytetrafluoroethylene (PTFE) such as Teflon®, silicone coated latex, or silicone. can. In one embodiment, tube 1222 is formed from thermoplastic polyurethane.

Spiral Coil Retaining Portion Referring now to FIGS. 10A-10E, an exemplary retaining portion 1230 comprises helical coils 1280,1282,1284. In some examples, the retaining 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 FIGS. 10A-10D, in some embodiments, the first coil 1280 comprises a half coil extending from 0 degrees to 180 degrees around the curvilinear central axis A of the retaining portion 1230 . In some embodiments, the curvilinear central axis A is substantially straight and coextensive with the curvilinear central axis of tube 1222, as shown. In other examples, the curvilinear central axis A of the retaining portion 1230 can be curved, giving the retaining portion 1230 a conical container shape, for example. 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 extends 180 degrees to 540 degrees along the retaining portion 1230, having a diameter D2 of about 5 mm to 50 mm, preferably about 10 mm to 20 mm, more preferably about 14 mm±2 mm. can be a coil. The third coil 1284 can be a full coil extending 540-900 degrees and having a diameter D3 of 5 mm and 60 mm, preferably about 10 mm-30 mm, more preferably about 18 mm±2 mm. In other examples, multiple coils 1282, 1284 can have the same inner and/or outer diameter. For example, each of the complete coils 1282, 1284 can have an outer diameter of about 18±2 mm.

In some examples, the overall height H of the retaining 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 is about 0.25 mm to 2.5 mm, more preferably about 0.5 mm to 2.0 mm.

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

Retention portion 1230 moves between a retracted position, in which retention portion 1230 is straight for insertion into the patient's urinary tract, and a deployed position, in which retention portion 1230 comprises helical coils 1280, 1282, 1284. It is possible to Generally, tube 1222 is naturally biased toward the coiled configuration. For example, an uncoiled or substantially straight guidewire can be inserted through the retaining portion 1230 to maintain the retaining portion 1230 in its linear retracted position, eg, as shown in FIGS. 11-14. When the guidewire is removed, retaining portion 1230 naturally transitions to its coiled position.

In some embodiments, the openings 1232, 1233 are located essentially only on the radially inwardly facing side 1286 or the protected or inner surface area 1000 of the coils 1280, 1282, 1284 or only on that side. to prevent occlusion or obstruction of the openings 1232,1233. The radially outwardly facing sides 1288 of the coils 1280, 1282, 1284 may be essentially free of openings 1232. In a similar embodiment, the total area of openings 1232 , 1233 on inwardly facing side 1286 of retaining portion 1230 is less than the total area of openings 1232 on radially outwardly facing side 1288 of retaining portion 1230 . can be substantially exceeded. Thus, when a negative pressure is induced in the ureter and/or renal pelvis, the mucosal tissue of the ureter and/or kidney can be pulled against retaining portion 1230, resulting in outer perimeter 1002 or protective surface area 1001 of retaining portion 1230. Some openings 1232 on top may be occluded. However, openings 1232 located on radially inwardly facing side 1286 of retaining portion 1230 or on protected or inner surface area 1000 may prevent such tissue from reaching outer perimeter 1002 or protected surface area 1001 of retaining portion 1230 . Not significantly occluded when touched. Accordingly, the risk of tissue injury from pinching or contact with the discharge opening 1232 can be reduced or eliminated.

Pore or Aperture Distribution Embodiments In some embodiments, the first coil 1280 can be devoid or essentially devoid of apertures 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 of the complete coils 1282,1284. Examples of various arrangements of openings or openings 1232 that can be used for coiled retaining portions (such as coiled retaining portion 1230 shown in FIGS. 10A-10E) are illustrated in FIGS. 11-14. As shown in FIGS. 11-14, the retaining portion 1330 is depicted in its uncoiled or straight position as occurs when a guidewire is inserted through the drainage lumen.

An exemplary retaining portion 1330 is illustrated in FIG. To more clearly describe the positioning of the openings of the retaining portion 1330, the retaining portion 1330 is referred to herein as the most proximal or first section 1310, the second section 1312, the third section 1314, the fourth section 1316 , fifth section 1318 , and distal-most or sixth section 1320 . Those skilled in the art will appreciate that fewer or additional partitions can be included as desired. As used herein, “sections” refer to discrete lengths of tube 1322 within retaining portion 1330 . In some examples, the segments are equal in length. In other examples, some segments can have the same length and other segments can have different lengths. In other embodiments, each segment has a different length. For example, segments 1310, 1312, 1314, 1316, 1318, and 1320 can each have a length L1-L6 ranging from about 5 mm to about 35 mm, preferably from about 5 mm to 15 mm.

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

In some embodiments, such as the retaining portion 1230 shown in FIGS. 10A-10E, the first or half coil 1280 extending from 0 to about 180 degrees of the retaining portion 1230 is void or essentially can not. The second coil 1282 can include a first section 1310 that extends approximately 180-360 degrees. The second coil 1282 can also include second and third segments 1312 , 1314 positioned between approximately 360 degrees and 540 degrees of the retaining portion 1230 . The third coil 1284 can include fourth and fifth segments 1316, 1318 positioned between approximately 540 and 900 degrees of the retaining portion 1230. As shown in FIG.

In some examples, 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. can. Similarly, if the retaining portion 1330 further comprises a third section 1314, the openings of the third section 1314 have a total area greater than the total area of the openings of the first section 1310 or the second section 1312. can have The openings in fourth section 1316, fifth section 1318, and sixth section 1320 also have a gradually increasing total area and/or number of openings to improve fluid flow through tube 1222. You may

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

As described herein, openings 1332, 1334, 1336, 1338, 1340 allow negative pressure to be applied to drainage lumen 1224 of catheter 1212, e.g., from proximal portion 1228 of drainage lumen 1224. When doing so, it can be positioned and sized such that the volumetric flow rate of fluid passing through the first opening 1332 more closely corresponds to the volumetric flow rate of the openings in the more distal section. As explained above, when each opening is of the same area, when a negative pressure is applied to the exhaust lumen 1224, the volumetric flow rate of fluid passing through the proximal-most of the first opening 1332 is: It will substantially exceed the volumetric flow rate of fluid passing through opening 1334 closer to distal end 1220 of retaining portion 1330 . While not intending to be bound by any theory, when negative pressure is applied, the pressure difference between the interior of the drainage lumen 1224 and the exterior of the drainage lumen 1224 will increase the pressure at the most proximal opening. It is believed to be larger in area and decrease at each opening moving towards the distal end of the tube. For example, the size and location of openings 1332 , 1334 , 1336 , 1338 , 1340 may be such that the volumetric flow rate for fluid flowing into openings 1334 of second section 1312 is less than that of openings 1332 of first section 1310 . It can be selected to be at least about 30% of the volume flow rate of the fluid flowing therein. In another embodiment, the volumetric flow rate for fluid flowing into the proximal-most or first segment 1310 is less than about 60% of the total volumetric flow rate for fluid flowing through the proximal portion of the evacuation lumen 1224. . In other examples, the volumetric flow rate for fluid flowing into openings 1332, 1334 of the two most proximal segments (eg, first segment 1310 and second segment 1312) is at a negative pressure, eg, about When a negative pressure of −45 mmHg is applied to the proximal end of the drainage lumen, the volumetric flow rate of fluid flowing through the proximal portion of the drainage lumen 1224 can be less than about 90%.

As will be appreciated by those skilled in the art, the volume 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 either the actual measurement of the volume flow rate downstream of and adjacent to each opening or the "calculated volume flow rate" described below. Implying the use of methods.

For example, actual measurements of fluid volume dispensed over time can be used to determine the volumetric flow rate through each opening 1332, 1334, 1336, 1338, 1340. FIG. In one exemplary experimental arrangement, a multi-chamber container with individual chambers sized to receive the sections 1310, 1312, 1314, 1316, 1318, 1320 of the retaining portion 1330 is arranged around the retaining portion 1330. It can be sealed and encapsulated. 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 an individual chamber into tube 3222 is measured and drawn into each opening over time when negative pressure is applied. The amount of fluid volume to be withdrawn can be determined. The cumulative amount of fluid volume collected in tube 3222 by the negative pressure pump system will be comparable to the sum of 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 calculated mathematically using equations for modeling fluid flow through tubular bodies. can be done. For example, the volume flow rate of fluid passing through openings 1332, 1334, 1336, 1338, 1340 and into exhaust lumen 1224 is described in detail below in connection with a mathematical example and FIGS. 15A-15C. can be calculated based on mass transfer shell balance estimates. The steps for deriving the mass balance equation and calculating the flow distribution between or associated with the openings 1332, 1334, 1336, 1338, 1340 are also described in detail below in connection with FIGS. 15A-15C. be done.

Another exemplary retaining portion 2230 with openings 2332, 2334, 2336, 2338, 2340 is illustrated in FIG. As shown in FIG. 12, the retention portion 2230 includes a number of 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. can be done. As shown in FIG. 12, the retaining portion 2330 comprises six sections 2310, 2312, 2314, 2316, 2318, 2320 as described above, each section having 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 segment increases as the total area of openings 1332 within each segment increases relative to proximally adjacent segments. increases toward the distal end 2220 of the tube 2222 so as to increase.

As shown in FIG. 12, the openings 2332 of the first section 2310 are arranged along a first imaginary line V1 that is substantially parallel to the curved central axis X1 of the retaining portion 2230. As shown in FIG. 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, respectively, the openings 2334, 2336, 2338 of these sections; 2340 are also positioned on the sidewall of tube 2222 in increasing number of rows to align around the circumference of tube 2222 . For example, some of the openings 2334 in the second section 2312 are aligned 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. Positioned. For example, the second section 2312 can include two or more rows of perforations or openings 2334, each opening 2334 having equal or different cross-sectional areas. Further, in some embodiments, at least one of the columns of second section 2312 is parallel to curvilinear central axis X1 of tube 2222, but not coextensive with first imaginary line V1. 3 can be aligned along a virtual line V3. Similarly, the third section 2314 can comprise five rows of perforations or openings 2336, each opening 2336 having an equal or different cross-sectional area, and the fourth section 2316 can comprise seven rows of perforations or openings. Section 2338 can be provided and fifth section 2318 can be provided with nine rows of perforations or openings 2340 . As in the previous embodiment, sixth section 2320 comprises a single opening, namely open distal end 2220 of tube 2222 . In the example of FIG. 12, the openings each have the same area, but the area of one or more of the openings can vary, as desired.

Another exemplary retaining portion 3230 with openings 3332, 3334, 3336, 3338, 3340 is illustrated in FIG. The retaining portion 3230 of FIG. 13 includes a plurality of similarly sized perforations or openings 3332, 3334, 3336, 3338, 3340. As shown in FIG. As in the previous example, the retaining portion 3230 can be divided into six sections 3310, 3312, 3314, 3316, 3318, 3320, each comprising at least one opening. The proximal-most or first section 3310 includes one opening 3332 . Second section 3312 includes two openings 3334 aligned along an imaginary line V2 extending around the circumference of the sidewall of tube 3222 . The third section 3314 comprises a group of three openings 3336 positioned at the vertices of an imaginary triangle. The fourth section 3316 comprises a group of four openings 3338 positioned at the corners of the virtual square. Fifth section 3318 includes ten openings 3340 positioned to form a diamond shape on the side wall of tube 3222 . As in the previous embodiment, sixth section 3320 comprises a single opening, namely open distal end 3220 of 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, but the area of one or more of the openings can vary, as desired.

Another exemplary retaining portion 4230 with openings 4332, 4334, 4336, 4338, 4340 is illustrated in FIG. Openings 4332, 4334, 4336, 4338, 4340 of retaining portion 4330 have different shapes and sizes. For example, first section 4310 includes a single circular opening 4332 . Second section 4312 has a circular opening 4334 with a larger cross-sectional area than opening 4332 of first section 4310 . Third section 4314 includes three triangular openings 4336 . Fourth section 4316 includes a large circular opening 4338 . Fifth section 4318 includes diamond-shaped opening 4340 . As in the previous embodiment, sixth section 4320 comprises an open distal end 4220 of tube 4222 . FIG. 14 illustrates an example of an arrangement of differently shaped openings within each section. It is understood that the shape of each opening within each segment can be independently selected, for example, the first segment 4310 can have one or more diamond-shaped openings or other shapes. sea bream. The area of each opening can be the same or different and can range from about 0.001 mm ² to about 2.5 mm ² .

(Example)
Calculation of Volumetric Flow Rate and Percentage of Flow Distribution Having described various arrangements of openings for the retention portion of the ureteral catheter 1212, the calculated percentage of flow distribution and the calculated volumetric flow rate through the catheter are calculated. Methods for determining will now be described in detail. A schematic diagram of an exemplary catheter is shown in FIG. 16, with side wall openings indicating the location of portions of the tube or drainage lumen used in the calculations below. The calculated percentage of flow distribution refers to the percentage of total fluid flowing through the proximal portion of the drainage lumen that enters the drainage lumen through different openings or segments of the retention portion. The calculated volumetric flow rate refers to the fluid flow rate per unit time through different portions of the retention portion's drainage lumen or opening. For example, the volumetric flow rate for the proximal portion of the drainage lumen describes the flow rate for the total amount of fluid passing through the catheter. Volumetric flow rate for an aperture refers to the volume of fluid that passes through the aperture and 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 drainage lumen. For example, an opening with 100% flow distribution means that all fluid entering the drainage lumen has passed through the opening. An opening with a distribution of 0% would indicate that the fluid in the drain lumen did not enter the drain lumen through that opening.

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

For the calculations below, a tube 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 and had a coefficient of friction μ of 8.02 x 10 -3 Pa·S (8.02 x 10 -3 kg/s·m) at 37°C. The urine volume flow rate through the catheter was 2.7 ml/min (Q _Total ) as determined by experimental measurements.

The calculated volume flow rate is through all perforations or openings 1232 of the five segments of the retention portion (referred to herein as volume flow rates Q ₂ -Q ₆ ) and through the open distal end 1220. (referred to herein as the volumetric flow rate Q ₁ ), the sum of the volumetric flow rates is the proximal end of tube 1222 at a distance of 10 cm to 60 cm from the last proximal opening, as shown in Equation 2. determined by the volumetric mass balance equation, equal to the total volumetric flow rate (Q _Total ) exiting from .
_QTotal = _Q1 + _Q2 + _Q3 + _Q4 + _Q5 +Q6 (equation ₂ )

The modified loss factor (K') for each segment considered three types of loss factors in the catheter model: the resulting pressure loss at the pipe inlet (e.g., the opening and open distal end of tube 1222). It is based on an inlet loss factor, a friction loss factor that accounts for the pressure loss resulting from friction between the fluid and the pipe wall, and a flow confluence loss factor that accounts for the pressure loss resulting from the interaction of the two flows into one.

The inlet loss factor depends on the shape of the orifice or opening. For example, a tapered or nozzle-shaped orifice would increase the flow rate into the exhaust lumen 1224 . Similarly, sharp-edged orifices will have different flow properties than orifices with poorly defined edges. For the purposes of the following calculations, it is assumed that opening 1232 is a side orifice opening and open distal end 1220 of tube 1222 is a sharp-edged opening. The cross-sectional area of each opening is assumed to be constant through the tube sidewall.

The friction loss factor approximates the pressure loss resulting from friction between the fluid and the adjacent inner wall of tube 1222 . Friction loss is defined according to the following equation.

The flow merge loss factor is derived from the loss factor for combining flows at a 90 degree divergence angle. Values for the loss factor were obtained from charts 13.10 and 13.11 of Miller DS, Internal Flow Systems, 1990 (incorporated herein by reference). The chart shows the ratio of the inlet orifice area (referred to as A1 in the chart) to the pipe cross-sectional area (referred to as A3 in the chart) and the inlet orifice volume flow rate (Q1 in the chart) and the resulting combined pipe The ratio of the volumetric flow rate (Q3 on the chart) is used. For example, for an area ratio of 0.6 between the area of the opening and the area of the drain lumen, the following flow confluence loss coefficients (K ₁₃ and K ₂₃ ) would be used.

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

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

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

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

The loss factor between Station B (flow through the exhaust lumen in the fifth segment 1318) and Station C (flow through the lumen in the fourth segment 1316) is given by equations 5.1 and 5.2 is calculated in a similar fashion, as indicated by For example, for Path 1 (Station B to Station C), the modified loss factor (K') for the opening of fourth section 1316 is defined as follows.

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

As with the previous station, the modified loss factors for both path 1 and path 2 ensure that the volumetric flow rates (Q ₁ , Q ₂ , and Q ₃ ) reflect the equilibrium distribution in the manifold up to station C. must be equalized so that Depending on the equalization of the two modified loss factors, we can then proceed to equalize the two paths to reach station D, station E and station F. The stepwise solution process proceeds through each station, as demonstrated, until calculating the modified loss factor for the final station, in this case station F. A total loss factor (K) for the manifold can then be calculated using the actual Q _Total (volumetric flow rate through the proximal portion of the exhaust lumen) determined through experimental measurements.

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

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

(Example 1)
Example 1 illustrates the distribution of fluid flow in retention member tubes with different size openings corresponding to the embodiment of retention member 1330 shown in FIG. As shown in Table 3, the most proximal opening (Q6) has a diameter of 0.48 mm and the distal most opening (Q5) on the side wall of the tube has a diameter of 0.88 mm; The open distal end (Q6) of the tube had a diameter of 0.97 mm. Each opening 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 is multiplied by the actual total volumetric flow rate (Q _Total ) to give the flow rate through each perforation and distal end hole. Judged. Alternatively, the calculated results can be presented as a percentage of 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 going from the proximal region to the distal region of the retaining portion of the vessel results in a more evenly distributed flow across the entire retaining portion.

(Example 2)
In Example 2, each opening has the same diameter and area. As shown in Table 4 and Figure 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%. Thus, 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 broader flow distribution with a greater percentage of fluid entering the drainage lumen through openings other than the most proximal opening. Accordingly, fluid can be collected more efficiently through multiple openings, reducing fluid congestion and improving the distribution of negative pressure through the renal pelvis and/or kidney.

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

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

In some examples, the distal portions 5004, 5005 comprise open distal ends 5010, 5011 for drawing fluid into the exhaust lumens 5002, 5003. The distal portions 5004, 5005 of the ureteral catheters 5000, 5001 further include retention portions 5012, 5013 for maintaining the distal portions 5004, 5005 of the drainage lumens or tubes 5002, 5003 within the ureters and/or kidneys. Prepare. The retention portions 5012, 5013 can be flexible and/or bendable to allow positioning of the retention portions 5012, 5013 within the ureter, renal pelvis, and/or kidney. For example, the retention portions 5012, 5013 are desirably sufficiently bendable to absorb forces imparted on the catheters 5000, 5001 and prevent such forces from being transmitted to the ureter. Further, when the retention portions 5012, 5013 are pulled toward the patient's bladder 10 in the proximal direction P (shown in FIG. 17), the retention portions 5012, 5013 are pulled out through the ureters 6,8. Additionally, it can be flexible enough to begin to unroll, straighten, or collapse.

In some examples, the retaining 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, discussed in detail below. Generally, the funnel-shaped support comprises at least one side wall. At least one sidewall of the funnel-shaped support has 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 drainage lumen or proximal portion of the drainage tube is essentially free or free of openings. While not intending to be bound by any theory, when negative pressure is applied to the proximal end of the proximal portion of the drainage lumen, the opening within the drainage lumen or proximal portion of the drainage tube Such openings may be undesirable because they may reduce the negative pressure at the distal portion of the ureteral catheter and thereby reduce the withdrawal or flow of fluid or urine from the kidney and renal pelvis of the kidney. it is conceivable that. Fluid flow from the ureters and/or kidneys is desirably not impeded by obstruction of the ureters and/or kidneys by the catheter. Also, without intending to be bound by any theory, when a negative pressure is applied to the proximal end of the proximal portion of the drainage lumen, the ureteral tissue will may be drawn against or into the opening along the ridge, which is thought to be capable of inflaming the tissue.

Several examples of ureteral catheters comprising retention portions comprising 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 support is formed by a coil of tubing. In FIGS. 17-41C, another embodiment of a funnel-shaped support is shown. Each of these funnel-shaped supports according to the invention will be discussed in detail below.

18A-D, a distal portion 5004 of a ureteral catheter is shown, generally designated 5000, in some embodiments. Distal portion 5004 comprises a retaining portion 5012 that constitutes a funnel-shaped support 5014 . Funnel-shaped support 5014 comprises at least one sidewall 5016 . As shown in FIGS. 18C and 18D, outer perimeter 1002 or protective surface area 1001 comprises outer surface or outer wall 5022 of funnel-shaped support 5014 . One or more drain 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 discharge hole 5030 in 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 comprises a first (outer) diameter D4 and a second (outer) diameter D5, wherein the first outer diameter D4 is less than the second outer diameter D5. is. 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 drainage lumen 5002 than the first outer diameter D4. In some examples, the first outer diameter D4 can range from about 0.33 mm to 4 mm (about 1 Fr to about 12 Fr (French catheter scale)) or about 2.0±0.1 mm. In some examples, the second outer diameter D5 exceeds the first outer diameter D4 and can range from about 1 mm to about 60 mm, or from about 10 mm to 30 mm, or from about 18 mm±2 mm.

In some examples, at least one sidewall 5016 of the funnel-shaped support 5014 can further comprise a third diameter D7 (shown in FIG. 18B), the third diameter D7 It is less than diameter D5. A third diameter D7 of the funnel-shaped support 5014 is closer to the distal end 5010 of the distal portion 5004 of the drainage lumen 5002 than the second diameter D5. The third diameter D7 is discussed in more detail below with respect to the margin. In some examples, 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 has a first (inner) diameter D6. First inner diameter D6 is closer to proximal end 5017 of funnel-shaped support 5014 than 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 examples, the overall height H5 of the sidewalls 5016 along the central axis 5018 of the retaining portion 5012 can range from about 1 mm to about 25 mm. In some embodiments, the sidewall height H5 may vary on different portions of the sidewall, for example, if the sidewall has wavy or rounded edges as shown in FIG. In some examples, undulations can range from about 0.01 mm to about 5 mm or more, as desired.

In some examples, the funnel-shaped support 5014 can have a generally conical shape, as shown in FIGS. 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 drainage lumen 5002 adjacent the base portion 5024 of the funnel-shaped support 5014 is 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 about the circumference of the funnel-shaped support 5014, as shown in FIG. 22A, where the angle 5020 ranges from about 140 degrees to about 180 degrees.

In some examples, the edge or margin 5026 of the distal end 5010 of the at least one sidewall 5016 can be rounded, square, or any shape desired. The shape defined by edge 5026 can be, for example, circular (as shown in FIGS. 18C and 23B), elliptical (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 in which at least one side wall 5302 comprises a plurality of lobe-shaped longitudinal folds 5304 along the length L7 of the side wall 5302. As shown in FIG. The outer perimeter 1002 or protective 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 drainage hole in 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 silicones, polymers, solid materials, fabrics, or permeable meshes to provide the desired leaf-like shape. Folded portion 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 can vary, and can range from about 0.5 mm to about 5 mm.

29A and 29B, one or more folds 5304 can comprise at least one longitudinal support member 5308. As shown in FIG. The longitudinal support member 5308 can span the entire length L7 or a portion of the length L7 of the funnel support 5300. FIG. The longitudinal support member 5308 can be formed from a flexible but partially rigid material such as a temperature sensitive shape memory material, eg, nitinol. The thickness of the longitudinal support member 5308 can range from about 0.01 mm to about 1 mm, as desired. In some examples, 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 follow the inner surface 5310 of the funnel-shaped support 5300 and into the drainage lumen 5312 . In other embodiments, the folded portion 5304 is formed from various rigid or partially rigid sheets or materials that are bent or molded to form a funnel-shaped retaining portion.

30 and 31, the distal end or edge 5400 of the fold 5402 can comprise at least one edge support member 5404. As shown in FIG. The edge support member 5404 can span the entire circumference 5406 of the distal edge 5400 of the funnel support 5408 or one or more portions of the circumference 5406 . Edge support member 5404 may be formed from a flexible but partially rigid material such as a temperature sensitive shape memory material, for example Nitinol. The thickness of edge support member 5404 can range from about 0.01 mm to about 1 mm, as desired.

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

Referring now to Figures 24A-C, in some examples, the edge 5200 of the distal end 5202 of the at least one sidewall 5204 can be shaped. For example, edge 5200 can comprise a plurality of generally rounded edges 5206 or sectors, eg, from about 4 to about 20 or more rounded edges. The rounded edge 5206 provides a larger surface area than a straight edge and can help support tissue of the renal pelvis or kidney and prevent obstruction. Edge 5200 can have any shape desired, but is preferably essentially free or free of sharp edges to avoid injured tissue.

In some embodiments, such as shown in FIGS. 18A-C and 22A-23B, funnel-shaped support 5014 comprises a base portion 5024 adjacent distal portion 5004 of drainage lumen 5002 . The base portion 5024 includes an inner lumen 5032 of the drainage lumen 5002 of the proximal portion 5006 of the drainage lumen 5002 for allowing fluid flow into the inner lumen 5032 of the proximal portion 5006 of the drainage lumen 5002 . at least one internal opening 5030 aligned with the . In some examples, the cross-section of opening 5030 is circular, but the shape may vary, such as oval, triangular, square, and the like.

In some embodiments, such as shown in FIGS. 22A-23B, central axis 5018 of funnel-shaped support 5014 is offset relative to central axis 5034 of proximal portion 5006 of drainage lumen 5002 . The offset distance X from the central axis 5018 of the funnel-shaped support 5014 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 base portion 5024 has a diameter D8 ranging from about 0.05 mm to about 4 mm (eg, shown in FIGS. 18C and 23B). In some examples, the diameter D8 of the inner opening 5030 of the base portion 5024 is approximately equal to the first inner diameter D6 of the adjacent proximal portion 5006 of the drainage 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 is between about 1:25 and Ranging from about 5:1.

In some embodiments, the 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 and the height H5 of the 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 of at least one sidewall 5016 of the funnel-shaped support 5014 (eg, shown in FIG. 18B) is between about 0.01 mm and about 1.9 mm or between about 0.5 mm and about 1 mm. can range from Thickness T1 can be generally uniform throughout 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 drainage lumen 5002 than the base portion 5024 of the funnel-shaped support 5014 .

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

In some embodiments, at least one sidewall 5016 of the funnel-shaped support 5014 is formed from a balloon 5100, eg, as shown in Figures 35A, 35B, 38A, and 38B. Balloon 5100 can have any shape that provides funnel-like support and prevents residual obstruction of the ureter, renal pelvis, and/or kidney. As shown in FIGS. 35A and 35B, balloon 5100 has the shape of a funnel. The balloon can be inflated after insertion or deflated before removal by adding or removing gas or air through 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 be adjacent the interior 5106 or the exterior 5108 of the adjacent portion of the proximal portion 5006 of the evacuation lumen 5002. can be surrounded. The diameter D9 of the sidewall 5110 of the balloon 5100 can range from about 1 mm to about 3 mm, with the sidewall tapering toward the distal end 5112 of the funnel-shaped support 5116 or proximally having a uniform diameter. It can vary along its length such that it tapers towards the 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 funnel-shaped support 5014 is continuous along height H5 of at least one sidewall 5016, eg, as shown in FIGS. 18A, 19, 20, and 21. do. In some examples, at least one sidewall 5016 of the funnel-shaped support 5014 comprises a solid wall, eg, the sidewall 5016 is non-porous through the sidewall even after 24 hours of contact with fluid, such as urine, on one side. Permeable.

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

As used herein, "opening" or "hole" means a continuous void space or channel through the sidewall from the outside to the inside of the sidewall or vice versa. In some examples, each of the at least one openings can have an area that 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 aperture means the smallest or minimal planar area defined by the perimeter of the aperture. For example, the opening may be circular and have a diameter of about 0.36 mm (area of 0.1 mm ² ) on the outside of the sidewall, but only 0.05 mm (area of 0.002 mm ² ) inside the sidewall. Or having it at a point on the opposite side of the sidewall, "Area" would be 0.002 mm ² as it is the minimum or minimal planar area for flow through the opening in the sidewall. If the aperture is square or rectangular, the "area" will be the length times the width of the planar area. For any other shape, "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 a shape to fill the planar area of the opening, calculating the area of each shape, and adding the areas of each shape together.

In some examples, at least a portion of the sidewall comprises at least one (one or more) opening. Generally, the central axis of the opening can be substantially perpendicular to the planar outer surface of the sidewall, or the opening can be angled with respect to the planar outer surface of the sidewall. The dimensions of the bore of the opening may be uniform throughout its depth, or the width may increase, decrease, or alternate in width through the opening from the exterior surface of the sidewall to the interior surface of the sidewall. may vary along depth by either

9A-9E, 10A, 10E, 11-14, 27, 32A, 32B, 33, and 34, in some embodiments, at least a portion of the sidewalls comprise at least one (one or more ) opening. The opening can be positioned anywhere along the sidewall. For example, the openings may be positioned uniformly throughout the sidewall, or within a defined area of the sidewall, such as closer to the distal end of the sidewall, or closer to the proximal end of the sidewall, or along the length or circumference of the sidewall. can be positioned vertically or horizontally or in random groups along. Without 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 drainage lumen, the ureter, renal pelvis, and/or other renal tissue may be directly affected. Adjacent openings in the proximal portion of the funnel-shaped support reduce the negative pressure in 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. Such an opening would not be desirable, as it could cause the tissue to become irritated and possibly inflame the tissue.

The number of openings can vary from 1 to 1000 or more as desired. For example, in FIG. 27, six openings (three on each side) are shown. As discussed above, in some examples, each of the at least one openings can be the same or different and can range from about 0.002 mm ² to about 50 mm ² or from about 0.002 mm ² to about 10 mm ² . , can have an area.

In some examples, the opening 5500 can be positioned closer to the distal end 5502 of the side wall 5504, as shown in FIG. In some examples, the opening is positioned in the distal half 5506 of the sidewall toward the distal end 5502 . In some examples, 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 lies between the opening 5600 and the tissue. Alternatively or additionally, one or more openings 5600 can be positioned near the distal end of the inner sidewall as desired. Inner sidewall 5604 and outer sidewall 5606 can be connected by one or more supports 5608 or ridges that connect outer side 5610 of inner sidewall 5604 to inner side 5612 of outer sidewall 5606 .

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, protected surface area or inner surface area 1000 can be established by a variety of different shapes or materials. Non-limiting examples of protected or internal surface areas 1000 include, for example, internal portions 152, 5028, 5118, 5310, 5410 of funnels 150, 5014, 5116, 5300, 5408, 5508, 5614, 5702, 5802, 6000 , 5510, 5616, 5710, 5814, 6004, internal portions 164, 166, 168, 170, 338, 1281, 1283, 1285 of coils 183, 184, 185, 187, 334, 1280, 1282, 1284, porous material 5900 , 6002, the inner portions 162, 5710, 5814 of the meshes 57, 5704, 5804, or the inner portion 536 of the cage 530 with the protected discharge holes 533.

In some non-limiting examples, one or more protected vent holes, ports, or perforations 133, 1233 are positioned on protected surface area 1000. FIG. In response to the application of negative pressure therapy through the catheter, the urothelium or mucosal tissue 1003, 1004 of the retention portion 130, 330, 410, 500, 1230, 1330, 2230, 3230, 4230, 5012, 5013 of the catheter. Of the protected vents, ports, or perforations 133, 1233 conforming or collapsing onto the outer perimeter 189, 1002 or protected surface area 1001 and thereby positioned on the protected or inner surface area 1000 is prevented or blocked from occluding one or more of the renal pelvis and calyx and the drainage lumen 124, 324, 424, 524, 1224, 5002, thereby allowing the patent fluid column or flow to 5003, 5312, 5708, 5808.

In some embodiments, the retaining portion 130, 330, 410, 500, 1230, 1330, 2230, 3230, 4230, 5012, 5013 has an outwardly facing side 1288 and an inwardly facing side 1286. The outer perimeter 1002 or protected surface area 1001 comprises one or more helical coils with outward facing sides 1288 of the one or more helical coils and one or more protected vents, ports, or The perforations 133, 1233 are located on the inwardly facing side 1286 (protected surface area or inner surface area 1000) of one or more helical coils.

For example, a funnel shape as shown in FIG. 25 can create sidewalls 5700 that conform to the natural anatomy of the renal pelvis and prevent 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 passageways through which a fluid column may flow from the calyx into the drainage lumen 5708. . Similarly, the mesh configuration from FIG. 26 can also create a protected surface area 1000, such as the interior 5814 of mesh 5804, between the calyx and the drainage lumen 5808 of the catheter. The mesh 5704, 5804 comprises a plurality of openings 5706, 5806 for allowing fluid flow therethrough and into the drainage lumens 5708, 5808. In some examples, the maximum area of the opening is 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 be able to. Meshes 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 connected to the distal end of the funnel-shaped support. For example, as shown in FIG. 26, the funnel-shaped support 5802 has a cover portion 5810 that traverses and protrudes from the distal end 5812 of the funnel-shaped support 5802 . Prepare. The cover portion 5810 can have any shape desired, such as flat, convex, concave, wavy, and combinations thereof. Cover portion 5810 can be formed from mesh or any polymeric solid material, as discussed above. Covering portion 5810 can provide an outer perimeter 1002 or protective surface area 1001 to support soft tissue within the kidney region and help promote urine production.

In some embodiments, the funnel-shaped support is made of a porous material, eg, as shown 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 funnel-shaped. In some embodiments, such as FIG. 33, porous material 5900 is positioned within interior 5902 of sidewall 5904 . In some embodiments, such as FIG. 34, funnel-shaped support 6000 comprises a porous liner 6002 positioned adjacent interior 6004 of 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 within the porous material can be from about 0.002 mm ² to about 100 mm ² or less.

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

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

Retaining portion 130 of ureteral catheter 112 can be made from a variety of suitable materials capable of transitioning from a collapsed state to a deployed state. In one embodiment, retention portion 130 comprises a framework of tines or elongated members formed from a temperature sensitive shape memory material such as Nitinol. In some examples, 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 follow the inner surface 186 of the retention portion 130 and into the drainage lumen 124 . In other embodiments, the retaining portion 130 is formed from various rigid or partially rigid sheets or materials that are bent or shaped to form a funnel-shaped retaining portion, as illustrated in FIGS. 37A and 37B. be done.

In some examples, the retention portion of the ureteral catheter 112 can include one or more mechanical stimulation devices 191 for providing stimulation to nerves and muscle fibers in the adjacent tissue of the ureter and renal pelvis. can. For example, the mechanical stimulation device 191 can include a linear or annular actuator embedded within or mounted adjacent to a portion of the side wall of the catheter tube 122 and configured to emit low level vibrations. . In some embodiments, mechanical stimulation can be provided to a portion of the ureter and/or renal pelvis to complement or modify the therapeutic effect obtained by applying negative pressure. While not intending to be bound by theory, such stimulation may involve, for example, stimulating nerves associated with the ureters and/or renal pelvis and/or activating peristaltic muscles, thereby causing adjacent It is thought that it will affect organizations that Nerve stimulation and muscle activation can result in changes in pressure gradients or pressure levels within surrounding tissues and organs, which contribute to or, in some cases, the therapeutic benefits of negative pressure therapy. can improve.

38A and 38B, according to another embodiment, the retention portion 330 of the ureteral catheter 312 is formed within a helical structure 332 and an expandable element or balloon 350 positioned proximally of the helical structure 332 to provide a renal pelvis. and/or a catheter tube 322 having a distal portion 318 for providing additional retention within the fluid collection site. Balloon 350 can be inflated to a pressure sufficient to retain the balloon within the renal pelvis or ureter, but sufficiently low to avoid dilating 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 previous embodiments, helical structure 332 can be imparted by bending catheter tube 322 to form one or more coils 334 . Coil 334 can have a constant or variable diameter and height, as described above. Catheter tube 322 is further disposed on a side wall of catheter tube 322 such that urine is drawn into drainage lumen 324 of catheter tube 322, e.g. It has multiple drainage ports 336 that allow it to be directed out of the body through the drainage lumen 324 on the lateral side.

As shown in FIG. 38B, inflatable element or balloon 350 can comprise an annular balloon-like structure, eg, having a generally heart-shaped cross-section and comprising surface or cover 352 defining cavity 353 . Cavity 353 is in fluid communication with inflation lumen 354 that extends parallel to evacuation lumen 324 defined by catheter tube 322 . 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. . Inflatable element or balloon 350 can include a tapered inner surface 358 that extends longitudinally and radially inward toward catheter tube 322 . The inner surface 358 can be configured to direct urine to be drawn toward the catheter tube 322 and 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 perimeter of the inflatable element or balloon 350 . Inflatable 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.

Referring to FIGS. 39A-40C, in some examples, an assembly 400 including a ureteral catheter 412 with a retaining portion 410 is illustrated. Retaining portion 410 is formed from a porous and/or sponge-like material attached to distal end 421 of catheter tube 422 . The porous material can be configured to carry and/or absorb urine and direct the urine toward drainage lumen 424 of catheter tube 422 . The retaining portion 410 can be configured into a funnel-shaped support having an outer surface and an inner surface, with the outer perimeter 1002 or protective surface area 1001 comprising the outer surface of the funnel-shaped support and within the porous material. One or more drainage holes, ports, or perforations of can be located within the porous material or on the inner surface 426 of the funnel-shaped support.

As shown in FIG. 40, retention portion 410 can be a porous wedge-shaped structure configured for insertion and retention within the patient's renal pelvis. A porous material consists of a plurality of pores and/or channels. Fluid can be drawn through the channels and holes, 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 retaining portion 410 through the holes and/or channels and be expelled, for example, by capillary action, peristalsis, or as a result of the induction of negative pressure within the holes and/or channels. Lumen 424 is withdrawn toward distal opening 420 . In another embodiment, as shown in Figure 40, the retention portion 410 comprises a hollow funnel structure formed from a porous sponge-like material. As indicated by arrow A, fluid is directed along the inner surface 426 of the funnel structure and into the drainage lumen 424 defined by the catheter tube 422 . Fluid may also enter the funnel structure of retaining portion 410 through pores and channels in the porous sponge-like material of sidewall 428 . For example, suitable porous materials can include open cell polyurethane foams such as polyurethane ethers. Suitable porous materials also include, with or without antimicrobial additives such as silver, and with or without additives to modify material properties such as hydrogels, hydrocolloids, acrylics, or silicones, for example: Laminations of woven or nonwoven layers of polyurethane, silicone, polyvinyl alcohol, cotton, or polyester can be included.

Referring to FIG. 41, according to another embodiment, retention portion 500 of ureteral catheter 512 comprises expandable cage 530 . Expandable cage 530 comprises one or more longitudinally and radially extending hollow tubes 522 . For example, tube 522 can be formed from a resilient shape memory material such as Nitinol. Cage 530 is configured to transition from a collapsed state for insertion through the patient's urinary tract to an expanded state for positioning within the patient's ureter and/or kidney. Hollow tube 522 includes a plurality of exhaust ports 534 that may be positioned on the tube, for example, on its radially inwardly facing side. Ports 534 are configured to allow fluid to flow or be drawn through ports 534 into individual tubes 522 . Fluid drains through hollow tube 522 into drainage lumen 524 defined by catheter body 526 of ureteral catheter 512 . For example, fluid may flow along the path indicated by arrow 532 in FIG. In some embodiments, when negative pressure is induced in the renal pelvis, kidney, and/or ureter, the ureteral wall and/or a portion of the renal pelvis presses against the outwardly facing surface of hollow tube 522. can be towed by Drainage port 534 is positioned and configured such that it is not significantly occluded by ureteral structures in response to application of negative pressure to the ureter and/or kidney.

In some embodiments, a ureteral catheter comprising a funnel-shaped support is used to enter a patient's urinary tract and, more specifically, the renal pelvis area/kidney using a conduit through the urethra and into the bladder. can be expanded within The funnel-shaped support 6100 is retracted within the ureteral sheath 6102 in a collapsed state (shown in FIG. 36). To deploy a ureteral catheter, a medical practitioner would insert a cystoscope into the urethra to provide a channel for the tool 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 would potentially be removed and a "pusher tube" would be routed 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. A ureteral catheter is 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 the deployed position.

Exemplary Ureteral Stents:
Referring now to FIG. 1A, in some embodiments, ureteral stents 52, 54 have a proximal end 62, a distal end 58, a longitudinal axis, and a longitudinal axis from the proximal end to the distal end. and at least one drainage channel extending along and maintaining patency of fluid flow between the patient's kidney and bladder. In some examples, 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 sidewalls.

Some examples of ureteral stents 52, 54 that may be useful in the present systems and methods are the CONTOUR ^™ Ureteral Stent, the CONTOUR VL ^™ Ureteral Stent, the POLARIS ^™ Loop Ureteral Stent, and the POLARIS ^™ Ultra Ureteral Stent. , PERCUFLEX ^™ Ureteral Stent, PERCUFLEX ^™ Plus Ureteral Stent, and STRETCH ^™ VL Flexima Ureteral Stent, each commercially available from Boston Scientific Corporation (Natick, Massachusetts). Boston Scientific Corp. (July 2010), "Ureteral Stent Portfolio" (incorporated herein by reference). The CONTOUR ^TM and CONTOUR VL ^TM ureteral stents are constructed of a soft Percuflex ^TM material that softens at body temperature and is designed for an indwelling time of 365 days. Variable length coils on the distal and proximal ends allow one stent to fit different ureter 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 are the INLAY ^(R) Ureteral Stent, the INLAY ^(R) OPTIMA ^(R) Ureteral Stent, the BARDEX ^(R) Double Pigtail Ureteral Stent, and the FLUORO- ^4TM Silicone Ureteral Stent. vascular stents, respectively, C.I. R. Bard, Inc. (Murray Hill, NJ). "Ureteral Stents", http://www. bard medical. com/products/kidney-stone-management/ureteral-stents/ (January 21, 2018), incorporated herein by reference.

Stents 52, 54 can be deployed in one or both kidneys or areas of the kidney (renal pelvis or ureters adjacent to the renal pelvis) as desired. Typically, these stents have nitinol wires through them, are inserted through the urethra and bladder to the kidneys, and then the nitinol wires are withdrawn from the stent, allowing the stent to assume the deployed configuration. is expanded by Many of the above stents have planar loops 58, 60 on the distal end (for deployment within the kidney), and some also have planar loops 62, 64 on the proximal end of the stent. , which is deployed in the bladder. When the nitinol wires are removed, the stent assumes a pre-stressed planar 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 withdrawn 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 embodiments, for example, a ureteral stent 100 as shown in FIGS. 1-7 of WO2017/019974 and FIG. 3 herein (which is identical to FIG. 1 of WO2017/019974). are proximal end 102 , distal end 104 , longitudinal axis 106 , outer surface 108 , and inner surface 110 , extending along longitudinal axis 106 from proximal end 102 to 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 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) an essentially closed longitudinal orientation. a second orientation 113B (shown on the right in FIG. 59) comprising an at least essentially closed bore 118 or closed bore defining an exhaust channel 120 along the longitudinal axis 106 of the elongated body 101; , and deformable bore 111 is movable from a default orientation 113 A to a second orientation 113 B in response to a radial compressive force 122 being applied to at least a portion of outer surface 108 of body 101 .

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

In some embodiments, one or more fins 112 are made of a flexible material that is soft to moderately soft according to the Shore hardness scale. In some embodiments, body 101 is made of a flexible material that is medium to hard on the Shore hardness scale. In some examples, one or more fins have a hardness of about 15A to about 40A. In some embodiments, body 101 has a hardness of about 80A to about 90A. In some embodiments, one or more of the fins 112 and the body 101 are made of a flexible material that is medium-soft to medium-hard according to the Shore hardness scale, eg, having a hardness of about 40A to about 70A.

In some embodiments, one or more of the fins 112 and the body 101 are made of a flexible material that is medium-hard to hard according to the Shore hardness scale, eg, having a hardness of about 85A to about 90A.

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

In some examples, one or more fins 112 extend longitudinally from proximal end 102 to distal end 104 . In some embodiments, the stent has 2, 3, or 4 fins.

In some examples, body outer surface 108 has an outer diameter ranging from about 0.8 mm to about 6 mm or about 3 mm in default orientation 113A. In some examples, body outer surface 108 has an outer diameter ranging from about 0.5 mm to about 4.5 mm or about 1 mm in second orientation 113B. In some embodiments, 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 project from body outer surface 108 in a direction generally perpendicular to the longitudinal axis. .

In some examples, 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, ureteral stent 100 is purposefully adapted to a dynamic ureteral environment, and ureteral stent 100 includes a proximal end 102, a distal end 104, a longitudinal axis 106, and an outer an elongated body 101 comprising a surface 108 and an inner surface 110 defining a deformable bore 111 extending along a longitudinal axis 106 from proximal end 102 to distal end 104; wherein the deformable bore 111 has at least a default orientation 113A comprising (a) an open bore 114 defining a longitudinally open channel 116 and (b) a longitudinally essentially closed channel 120 defining at least a second orientation 113B comprising a bore 118 that is essentially closed, the deformable bore being deformed in response to a radial compressive force 122 being applied to at least a portion of the outer surface 108 of body 101; , from a default orientation 113A to a second orientation 113B, and the inner surface 110 of the body 101 has a diameter D, which means that the deformable bore 111 moves from the default orientation 113A to the second orientation 113B. , the diameter can be reduced to a point above which fluid flow through deformable bore 111 would be reduced. In some embodiments, diameter D is reduced by up to about 40% in response to deformable bore 111 moving from default orientation 113A to second orientation 113B.

Other examples of suitable ureteral stents are disclosed in US Patent Application Publication No. US2002/0183853A1, which is incorporated herein by reference. In some embodiments, for example, FIGS. 4, 5, and 7 of US2002/0183853A1 and FIGS. 4-6 herein (identical to FIGS. 1, 4, 5, and 7 of US2002/0183853A1). ), the ureteral stent has a proximal end 12, a distal end 14 (not shown), a longitudinal axis 15, and a longitudinal axis 15 from the proximal end 12 to the distal end 14. and maintain patency of fluid flow between the patient's kidneys and bladder (e.g., 26, 28, 30 in FIG. 4; 32, 34 in FIG. 5; 36, and 38, 48 in FIG. 6). In some embodiments, the at least one drainage channel is partially open along at least a longitudinal portion thereof. In some embodiments, at least one drainage channel is closed along at least a longitudinal portion thereof. In some embodiments, at least one drainage channel is closed along its longitudinal length. In some examples, the ureteral stent is radially compressible. In some examples, the ureteral stent is radially compressible to narrow at least one drainage channel. In some embodiments, elongated body 10 comprises at least one external fin 40 along longitudinal axis 15 of elongated body 10 . In some examples, the elongated body comprises 1-4 drainage channels. The diameter of the evacuation channel can be the same as described above.

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

In some embodiments, a system for inducing a negative pressure within a portion of a patient's urinary tract is provided, the system comprising: (a) a distal portion for insertion within the patient's kidney; (b) 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. (c) external to the patient's body for application of negative pressure through both the bladder catheter and the ureteral catheter, thereby drawing fluid from the kidneys into the urine; A pump is provided in the ductal catheter that is pulled through both the ureteral and bladder catheters and then out of the patient's body.

In some embodiments, a system for inducing a negative pressure within a portion of a patient's urinary tract is provided, the system comprising: (a) at least one ureteral catheter; at least one ureteral catheter comprising a distal portion for insertion and a proximal portion; (b) a distal portion for insertion within a patient's bladder; and receiving negative pressure from a negative pressure source. wherein at least one of the at least one ureteral or bladder catheter has (a) a proximal portion and (b) a distal portion; having one or more protected vents, ports, or perforations, and mucosal tissue occluding one or more of the protected vents, ports, or perforations in response to the application of negative pressure through the catheter; (c) a 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 and bladder catheters, and then out of the patient's body. source.

In some embodiments, a system for inducing a negative pressure within a portion of a patient's urinary tract, the system comprising: (a) at least one ureteral catheter inserted within the patient's kidney; and (b) a distal portion for insertion into a patient's bladder and a proximal portion for receiving a pressure differential. a bladder catheter, wherein the pressure differential causes fluid from the kidney to be drawn into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then out of the patient's body; is 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; (b) a distal portion comprising one or more protected drainage holes, ports or perforations such that mucosal tissue undergoes one or more protected drainage in response to application of a pressure differential through the catheter; a distal portion comprising a retaining portion configured to establish an outer perimeter or protective surface area to prevent occlusion of the hole, port or perforation.

1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, an exemplary system 1100 for inducing negative pressure within a patient's urinary tract to increase renal perfusion. , are shown. System 1100 comprises one or two ureteral catheters 1212 (or alternatively ureteral stents shown in FIG. 1A) connected to 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 . Kidneys 2, 4 are involved in hemofiltration and clearance of waste compounds from the body through urine. Urine or fluids produced by the right kidney 2 and left kidney 4 pass into the patient's bladder 10 through the right ureter 6 and left ureter 8, which are connected to the kidneys at renal tubules, ie renal pelvises 20, 21. Ejected. Urine can be conducted through the ureters 6, 8 by peristalsis of the ureter walls as well as by gravity. The ureters 6 , 8 enter the bladder 10 through the ureteral orifice or orifice 16 . Bladder 10 is a flexible, substantially hollow structure adapted to collect urine until it is excreted from the body. Bladder 10 is transitionable from an empty position (indicated by reference line E) to a full position (indicated by reference line F). Generally, when bladder 10 reaches a substantially full condition, fluid or urine is allowed to drain from bladder 10 to urethra 12 through urethral sphincter or opening 18 located in the lower portion of bladder 10 . Contractions of bladder 10 may respond to stresses and pressures exerted on triangular region 14 of bladder 10 , which is the triangular region extending between ureteral orifices 16 and urethral orifices 18 . The trigone region 14 is stress and pressure sensitive such that the pressure on the trigone region 14 increases as the bladder 10 begins to fill. When a threshold pressure on trigone region 14 is exceeded, bladder 10 begins to contract and expel collected urine through 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. A proximal portion of one or more of the catheters 1212 extends into the bladder, into the urethra, or out of the body. In some examples, 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. A proximal portion 1216 of bladder catheter 56 , 116 is connected to a source of negative pressure, such as fluid pump 2000 . The shape and size of the connector can be selected based on the type of pump 2000 being used. In some examples, the connector can be manufactured with distinctly different configurations so that it can only be connected to specific pump types, which can be used to transfer negative pressure to the patient's bladder, ureter, or Considered safe for intrarenal induction. In other examples, as described herein, the connector can be of a more universal configuration adapted for attachment to a variety of different types of fluid pumps. System 1100 is but one example of a negative pressure system for inducing negative pressure that can be used with the bladder catheters disclosed herein.

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

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

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

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

In some embodiments, such as those shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, bladder catheters 56, 116, such as the ureteral catheters discussed above, One or more drainage holes, ports, or perforations 142, 172 are disposed on the protected or inner surface area 1000 of the retention portion 123 such that in response to application of negative pressure, the mucosal tissue 1003, 1004 is released into the bladder catheter. 56,116 onto the outer perimeter 1002 or protective surface area 1001 of the retaining portion 173, thereby protecting one or more of the drainage holes, ports, or perforations 172 of the bladder catheter 56,116. is prevented or prevented from occluding the

1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, retaining portion 123 or deployable seal and/or anchor 136 is attached to distal end 148 of bladder catheter 116. located on or adjacent to Retaining portion 123 or deployable anchor 136 is configured to transition between a contracted state for insertion into bladder 10 through urethra 12 and urethral opening 18 and a deployed state. Retaining portion 123 or deployable anchor 136 is configured to be deployed within and seated adjacent to and/or against urethral opening 18 in the lower portion of bladder 10 . For example, retention portion 123 or deployable anchor 136 may be positioned adjacent urethral opening 18 to enhance suction of negative pressure applied to bladder 10 or to partially, substantially, or partially remove bladder 10 . A perfect seal can be provided to ensure that urine in the bladder 10 is directed through the drainage lumen 140 and prevent leakage into the urethra 12 . For bladder catheters 116 that include 8 Fr to 24 Fr extension tubes 138, the retention portion 123 or deployable anchor 136 can have a diameter in the deployed state of about 10 mm to about 100 mm.

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

In some embodiments, retention portion 123 comprises a coiled retention portion similar to the retention portion of urinary catheters described in connection with FIGS. 2A and 7A-14. In some embodiments, such as shown in FIGS. 1C-1E, 1U-1W, the coiled retaining portion 123 has an outer periphery 1002 or outer region of the helical coils 36, 38, 40 or 438, 436, 432 A protected drainage hole, port, or perforation 172 that contacts and supports bladder tissue 1004 and is positioned within the protected or inner surface area of helical coil 36, 38, 40 or 438, 436, 432. A plurality of helical coils 36, 38, 40 or 438, 436, 432 may be provided arranged to prevent occlusion or blockage of the.

The coiled retaining portion 123 has at least a first coil 36, 438 with an outer diameter D1 (see FIG. 1E), at least a second coil 38, 436 with an outer diameter D2, and an outer diameter D3. At least a third coil 40, 432 can be provided. The diameter D3 of the distal-most 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 coils 36, 38, 40 or 438, 436, 432 and/or step distances or heights between adjacent coils 36, 38, 40 or 438, 436, 432 may be regular or irregular. It can vary in a regular fashion. In some examples, the plurality of coils 36, 38, 40 or 438, 436, 432 can form a tapered or inverted pyramidal shape with D1>D2>D3. In some embodiments, the coiled retaining portion 123 can comprise a plurality of similarly sized coils, or, for example, a plurality of proximal similarly sized coils and a plurality of coils. and a distal-most coil having a smaller diameter than the other coils. The diameters of the coils 36, 38, 40, or 438, 436, 432, and the distance or height between adjacent coils, may be adjusted so that the retention portion 123 is maintained for a desired period of time, such as hours, days, or up to about six months. It is selected to remain in the bladder over the cycle. Coiled retention portion 123 may be large enough so that it remains within bladder 10 and does not pass into the urethra until the catheter is ready to be removed from 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 approximately 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 coiled tubing can range from about 0.33 mm to 9.24 mm (about 1 Fr to about 28 Fr (French catheter scale)).

The configuration, size and location of the holes, ports or perforations 142, 172 can be any of the configurations, sizes and locations discussed above for ureteral or other catheters. In some examples, holes, ports, or perforations 142 are present on outer perimeter 1002 or protected surface area 1001 and protected holes, ports, or perforations 172 are present on protected surface area or inner surface area 1000. exist. In some examples, outer perimeter 1002 or protected surface area 1001 is essentially free or free of holes, ports, or perforations 142, and protected holes, ports, or perforations 172 are protected surface areas or inner surfaces. It exists on a surface area of 1000.

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

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

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

In some examples, legs 214 comprise flexible tines that can 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, eg, diameter, of each leg can range from about 0.003 inch to about 0.035 inch.

In some embodiments, support cap 212 can be a flexible cover 216 mounted on and supported by legs 214 . Flexible cover 216 is formed from a flexible, soft, and/or elastic material such as silicone or Teflon(R) to prevent fluid from passing through cover 216, a porous material, or a combination thereof. can be In some examples, the flexible material significantly abrades the mucosal lining of the bladder wall or urethra when positioned adjacent to the mucosal lining, such as silicone or Teflon® materials or porous materials; Made from materials that do not irritate or damage. The thickness of cover 216 can range from about 0.05 mm to about 0.5 mm. In some embodiments, flexible cover 216 and legs 214 are sufficiently structured such that cover 216 and legs 214 maintain their shape when contacted by the upper wall or bladder tissue 1004 . rigid. Thus, legs 214 and flexible cover 216 prevent the bladder from collapsing and occluding the perforation on retention portion 6 and/or open distal end 30 of tube 12 . Legs 214 and flexible cover 216 also effectively keep the trigone area and ureteral orifice open so that negative pressure can draw urine into bladder and drainage tube 12 . As discussed herein, when the bladder is allowed to collapse excessively, a tissue flap extends across the ureteral orifice whereby negative pressure is applied to the ureteral catheter, ureteral stent, etc. , and/or from being transmitted to the ureter, thereby preventing the withdrawal of urine into the bladder.

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

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

Referring to FIG. 1J, bladder top wall support 210 includes support cap 212 and a plurality of legs 214 . As in the previously described embodiments, the bladder top wall support 210 can be positioned in a retracted position in which the support 210 is at least partially retracted within the conduit or tube 12 and deployed to support the top wall of the bladder. It can be moved between positions. In some embodiments, catheter device 10 also includes a drain tube 218 extending from open distal end 30 of conduit or tube 12 . Unlike the previously described embodiments, the support cap 212 shown in FIG. 4 includes an inflatable balloon 226 . Inflatable balloon 226 can be generally hemispherical and includes 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. be able to.

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

Referring to FIG. 1K, an exemplary retention portion 6, 123 of urine collection catheter device 10 including multiple coiled drainage lumens, generally represented as lumens 218, is illustrated. Retaining portion 6 comprises a tube 12 having a distal open end 30 . Drainage lumen 218 is positioned partially within tube 12 . In the deployed position, drainage lumen 218 is configured to extend from open distal end 30 of tube 12 and conform to a coiled orientation. Drainage lumens 218 may be distinct throughout the length of catheter device 10 or nest within a single drainage lumen defined by tube 12 . In some examples, the drainage lumen 218 can be a pigtail coil having one or more coils 244, as shown in FIG. Unlike the previously described embodiment, 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 axis C of tube 12 . In some embodiments, the drainage lumen 218 includes holes, ports, or perforations (similar to the perforations 132, 133 of FIGS. 9A or 9B) to draw fluid from the bladder into the interior of the drainage lumen 218. (not shown in FIG. 1K). In some examples, the perforations can be positioned on the radially inward facing side 240 and/or the outward facing side of the coiled portion of the discharge lumen. As previously explained, drainage lumen 218 or perforations located on the radially inward facing side of tube 12 are less likely to be occluded by the bladder wall during application of negative pressure to the bladder. . Urine can also be drawn directly into one or more drainage lumens defined by tube 12 . For example, rather than being drawn through perforations 230 and into drainage lumen 218 , urine can be drawn directly through open distal end 30 and into the drainage lumen defined by tube 12 .

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

In use, distal end 30a of catheter device 10a is inserted into the patient's bladder in a contracted position. Once inserted into the bladder, distal sheath 22a is released by sliding slidable collar 24a distally toward stationary collar 28a. Once distal sheath 22a is deployed, proximal sheath 20a is released or deployed in a similar fashion by sliding slidable collar 24a proximally toward discrete 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 distal sheath 22a caused by the collapse of the bladder is transmitted through support 32a to proximal sheath 20a, moving proximal sheath 20a toward the desired position adjacent the opening of the urethra. Once the proximal sheath 20a is in place, a seal over 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.

1N-1T, retention portion 123 contacts the upper wall of bladder 10 to prevent bladder 10 from contracting and occluding either fluid port 312 of catheter device 10 or the ureteral opening of the bladder. An inflatable support cap, such as an annular balloon 310, is positioned to prevent it. In some embodiments, distal end portion 30 of tube 12 extends through central opening 314 of balloon 310 . A distal end portion 30 of tube 12 may also contact the upper bladder wall.

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

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

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

Referring to FIG. 41, in another embodiment of a 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 outwardly from the catheter body of the bladder catheter, which in some embodiments is the ureter of FIG. It can be similar to that discussed above regarding the retention portion of the catheter. The member can be formed from a suitable elastic and shape memory material such as Nitinol. In the deployed position, the member or tines are imparted with sufficient curvature to define a spherical or ellipsoidal central cavity. A cage is attached to the open distal open end of the catheter tube or body to allow 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 inch). .

In some embodiments, the cage further comprises a shield or cover over a distal portion of the cage such that tissue, i.e. the distal wall of the bladder, is trapped or chewed as a result of contact with the cage or member. prevent or reduce the likelihood of 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 pinched or trapped, reduce patient discomfort, and protect the device during use. The cover can be formed, at least in part, from a porous and/or permeable biocompatible material such as a woven polymer mesh. In some examples, the cover encloses all or substantially all of the cavity. In some examples, the cover covers only about the distal two-thirds, about the distal half, or about the distal one-third portion, or any amount, of the cage 210 .

The cage and cover are transitionable from a collapsed position to a deployed position in which the members are tightly contracted together around the central portion and/or around the bladder catheter 116 to allow insertion through the catheter or sheath. For example, for cages constructed from shape memory materials, the cage can be configured to transition to the deployed position upon warming to a sufficient temperature, such as body temperature (eg, 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 catheters 112, 114 to the ureters. The open arrangement of member 212 or tines does not obstruct or occlude distal opening 248 and/or drainage port of bladder catheter 216, making manipulation of catheters 112, 114 easier to perform.

It should be appreciated 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 pump assembly 710, for example, by flexible tubing 166 that defines a fluid flow path.

Exemplary fluid sensor:
1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, in some embodiments, the system or assembly 100, 700, 1100 further includes a One or more sensors 174 are provided for monitoring physical parameters or fluid properties of the fluid or urine being collected. 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 with respect to FIG. 44, information obtained from sensors 174 is transmitted to a central data collection module or processor and external devices such as, for example, pump 710 (shown in FIG. 44). can be used to control the operation of The sensor 174 is integrally formed with one or more of the catheters 112, 114, 116, eg, embedded within the wall of the catheter body or tube and in fluid communication with the drainage lumens 124, 140. be able to. In other examples, one or more of the sensors 174 can be positioned within the internal circuitry of an external device such as a fluid collection reservoir 712 (shown in FIG. 44) or a pump 710 .

Exemplary sensors 174 that may be used with urine collection assembly 100 may comprise one or more of the following sensor types. For example, catheter assembly 100 can include a conductivity sensor or electrode that samples the conductivity of urine. The normal conductivity of human urine is about 5-10 mS/m. Urine with a conductivity outside the expected range may indicate that the patient is suffering from a physiological problem requiring further treatment or analysis. Catheter assembly 100 may also include a flow meter for measuring the flow rate of urine through catheters 112, 114, 116. FIG. Flow rate can be used to determine the total volume of fluid excreted from the body. Catheters 112, 114, 116 may also include thermometers for measuring urine temperature. Urine temperature can be used to cooperate with a conductivity sensor. Urine temperature can also be used for monitoring purposes, as a urine temperature outside the physiological normal range can indicate certain physiological conditions. In some examples, sensor 174 can be a urine analyte sensor configured to measure the concentration of creatinine and/or protein in urine. For example, various conductivity sensors and optical spectroscopy sensors may be used to determine analyte concentrations in urine. Sensors based on color changing reagent test strips may also be used for this purpose.

How to insert the system:
Having described system 100 comprising a ureteral catheter and/or ureteral stent and a bladder catheter, some examples of methods for insertion and deployment of ureteral stents or ureteral catheters and bladder catheters include: will be discussed in detail here.

In some embodiments, a method for inducing a negative pressure within a portion of a patient's urinary tract is provided, the method comprising deploying a ureteral catheter into the patient's ureter and connecting the patient's kidneys and maintaining patency of fluid flow to and from the bladder, the ureteral catheter comprising a distal portion for insertion into the patient's kidney and a proximal portion; and a bladder catheter. into 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 and applying a negative pressure to the proximal end of the bladder catheter to induce a negative pressure within a portion of the patient's urinary tract to remove fluid from the patient. including. In some embodiments, at least one of the ureteral or bladder catheter has (a) a proximal portion and (b) a distal portion and includes one or more protected drainage holes, ports. or perforations to establish an outer perimeter or protective surface area that prevents mucosal tissue from occluding one or more of the protected drainage holes, ports, or perforations in response to the application of negative pressure through the catheter. and a distal portion comprising a retention portion configured to.

Referring to FIG. 42A, an example of steps for positioning the system within a patient's body and optionally inducing a negative pressure within the patient's urinary tract, such as the bladder, ureters, and/or kidneys, is illustrated. be. As shown in box 610, a medical practitioner 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, and to the desired fluid collection location, such as the renal pelvis of the kidney, as shown in box 612 . Once the guidewire has been advanced to the desired fluid collection location, the ureteral stent or ureteral catheter of the present invention (examples of which are discussed in detail above) guides as shown in box 614. It is inserted over the wire into the fluid collection location. In some examples, the location of the ureteral stent or ureteral catheter can be confirmed by fluoroscopy, as indicated at box 616 . Once the location of the distal end of the ureteral stent or ureteral catheter is 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 completes the ureter and/or renal pelvis such that urine is allowed to pass from outside the catheter through the ureter and into the bladder. do not occlude. Moving the catheter may apply force against the urinary tract tissue, thus avoiding complete obstruction of the ureter and avoiding the application of force to the ureter sidewall, which can cause injury.

After the ureteral stent or ureteral catheter is in place and deployed, the same guidewire can be used to insert a second ureteral stent or second ureteral catheter using the same insertion and positioning methods described herein. ureteral catheters into other ureters and/or kidneys. For example, a cystoscope can be used to obtain visualization of other ureteral orifices within the bladder, with a guidewire passing through the visualized ureteral orifice to a fluid collection location within the other ureter. can be advanced. A second ureteral stent or a second ureteral 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. A cystoscope obtains visualization of the ureteral opening and advances a second guidewire into the second ureter and/or kidney to position a second ureteral stent or a second ureteral catheter. is used in the manner described above. Once the ureteral stent or catheter is in place, in some embodiments the guidewire and cystoscope are removed. In other examples, a cystoscope and/or guidewire can remain in the bladder to aid in placement of a bladder catheter.

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

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

In some examples, bladder catheters are replaced more frequently than ureteral stents or ureteral catheters. In some examples, multiple bladder catheters are placed and removed serially during the indwelling time for a single ureteral stent or catheter. For example, a doctor, nurse, caregiver, or patient can place a bladder catheter into the patient at home or in any healthcare setting. A plurality of bladder catheters are optionally included in the kit, along with instructions for placement, replacement, and optional connection or draining of the bladder catheters and the negative pressure source to a container, as needed, by medical personnel, patients, and receptacles. Or can be provided to a caregiver. In some examples, the negative pressure is applied nightly for a predetermined number of nights (such as 1 to 30 nights or more). Optionally, the bladder catheter can be changed nightly prior to application of negative pressure.

In some examples, urine is allowed to drain by gravity or peristalsis from the urethra. In another example, a negative pressure is induced within the bladder catheter to facilitate urine evacuation. Without intending to be bound by any theory, it is believed that some of the negative pressure applied to the proximal end of the bladder catheter is transmitted to the ureter, renal pelvis, or other portion of the kidney, where it is removed from the kidney. It is thought to facilitate the excretion of fluid or urine from the body.

Referring to FIG. 42B, steps for using the system for induction of negative pressure within the ureter and/or kidney are illustrated. After the ureteral stent or indwelling portion of the ureteral catheter and bladder catheter have been correctly positioned and any anchoring/retaining structures, if present, have been deployed, the outer proximal portion of the bladder catheter will be removed as shown in box 624 . The end is connected to a fluid collection or pump assembly. For example, a bladder catheter can be connected to a pump for inducing negative pressure in the patient's bladder, renal pelvis, and/or kidneys.

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 . Negative pressure is intended to counteract congestion-mediated interstitial hydrostatic pressure due to increased intra-abdominal pressure and consequent or increased renal venous or renal lymphatic pressure. The applied negative pressure can thus increase the flow of filtrate through the medullary tubules and reduce water and sodium reabsorption.

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

Exemplary Fluid Collection System:
Having described an exemplary system and method for positioning such a system within a patient's body, referring now to FIG. A system 700 for doing will be described. System 700 can comprise a ureteral stent and/or ureteral catheter, bladder catheter, or system 100 as described herein above. As shown in FIG. 44, bladder catheter 116 of system 100 is connected to one or more fluid collection reservoirs 712 for collecting urine drawn from the bladder. A fluid collection container 712 connected to the bladder catheter 116 uses an external fluid pump 710 and fluid to generate a negative pressure through the bladder catheter 116 and/or the ureteral catheters 112, 114 into the bladder, ureters, and/or kidneys. can communicate. As discussed herein, such negative pressure can 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 comprises a fluid lock or fluid barrier to allow air to enter the bladder, renal pelvis, or in the event of an accidental therapeutic or non-therapeutic pressure change. It can be prevented from entering the kidney. For example, the inflow and outflow ports of the fluid container can be positioned below the fluid level within the container. Thus, air is prevented from entering the medical tubing or catheter through either the inflow or outflow port of fluid container 712 . As discussed above, the external portion of the tubing extending between the fluid collection container 712 and the pump 710 includes one or more filters to allow urine and/or particulate matter to enter the pump 710. can be prevented.

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

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

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

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

With continued reference to FIG. 44, system 700 can further comprise a feedback device 720, such as a visual display or audio system, to provide information to the user. In some examples, feedback device 720 can be integrally formed with pump 710 . Alternatively, feedback device 720 can be a separate dedicated or multipurpose electronic device such as a computer, laptop computer, tablet PC, smart phone, or other handheld electronic device. Feedback device 720 is configured to receive the calculated or determined measurements from controller 714 and present the received information to the user via feedback device 720 . For example, 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 may measure the current flow rate of urine, temperature, current conductivity of urine in mS/m, total urine volume produced during the session, voided during the session. Configured to display total sodium content, other physical parameters, or any combination thereof.

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

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

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

Non-invasive patient monitoring sensors 724 can include pulse oximetry sensors, blood pressure sensors, heart rate sensors, and respiration sensors (eg, capnography sensors). 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 still other examples, a sensor may be associated with an extracorporeal blood system or circuit and configured to measure a parameter 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 extracorporeal blood system tubing to measure parameter values of the patient's blood as it passes through the tubing. Patient monitoring sensors 724 may be in wired or wireless communication with pump 710 and/or controller 714 .

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

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

Referring to Figures 45A and 45B, an exemplary pump 710 for use with the system is illustrated. In some examples, the pump 710 is configured to draw fluid from the catheters 112, 114 (eg, shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B) to about 10 mmHg or A micropump with less sensitivity or accuracy. Desirably, the pump 710 can provide a urine flow range of 0.05 ml/min to 3 ml/min over an extended period of time, such as from about 8 hours to about 24 hours/day, 1 to about 30 days, or longer. is. At 0.2 ml/min, approximately 300 mL of urine/day is expected to be collected by system 700 . The pump 710 can be configured to provide negative pressure to the patient's bladder, where the negative pressure is between about 0.1 mmHg and about 150 mmHg, or between about 0.1 mmHg and about 50 mmHg, or between about 5 mmHg and 20 mmHg (pump gauge pressure at 710). For example, 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. A peristaltic pump can also be used with system 700 . In other examples, a piston pump, vacuum bottle, or manual vacuum source can be used to provide the negative pressure. In another embodiment, the system can be connected to a wall suction source, such as those available in hospitals, through a vacuum regulator to reduce negative pressure to therapeutically appropriate levels.

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

In some examples, the pump 710 is configured for long-term use, thus, excluding bladder catheter replacement time, for example, from about 8 hours to about 24 hours/day, or from 1 to about 30 days, or more. It is possible to maintain precise aspiration over long cycles. Additionally, in some embodiments, the pump 710 is configured to be manually operated and include a control panel 718 that allows the user to set the desired suction value. Pump 710 can also include a controller or processor, which can be the same controller that operates system 700 or a separate processor dedicated to the operation of 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 additionally, operation of pump 710 can be controlled by a processor based on feedback received from a plurality of sensors associated with the catheter.

In some examples, the processor is configured to operate the pump 710 intermittently. For example, pump 710 may be configured to pulse negative pressure followed by periods in which no negative pressure is provided. In other examples, the pump 710 can be configured to alternate between providing negative and positive pressure, resulting in alternating flush and pump effects. 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.

Percutaneous urinary catheters and system urine can also be removed from the urinary tract through a percutaneous renal fistula or urethral bypass catheter deployed via percutaneous insertion into the patient's renal pelvis and/or kidney. . In some embodiments of the invention, such urethral bypass catheters provide negative and/or positive pressure therapy to the patient's renal pelvis and/or kidney to promote urine production and to It can be adapted to drain and/or conduct urine from the kidney to an external fluid collection container. Urethral bypass catheters may be used, for example, to remove fluids (eg, urine) from the body when a portion of the urinary tract (eg, the ureter or urethra) is blocked. Generally, such urethral bypass catheters are inserted into the patient's abdomen at a percutaneous access site. Such catheters extend through the kidney and optionally into the renal pelvis. A typical percutaneous access site for accessing the abdominal cavity and kidneys is about 0.5 cm to about 1.5 cm or about 1 cm below and about 0.5 cm to about 1.5 cm below the tip of the 12th rib. Located 5 cm or about 1 cm medial. Such an access site would provide easy access to the lower pole of the kidney and avoid damaging other abdominal organs (eg, colon, liver, and/or spleen). A physician inserting a urethral bypass catheter may also select other access sites on the patient's torso based on the patient's size and/or other therapeutic considerations.

Exemplary Urinary Catheter The deployable retention structure or portion of the bypass catheter is configured to retain the distal portion and/or tip of the catheter within the kidney, renal pelvis, and/or bladder. For example, any of the coils, funnels, expandable cages, balloons, and/or sponges described herein can be placed within the urinary tract (e.g., within the renal pelvis, ureter, and/or kidney) to the desired location. It can be used as a retention portion to keep the end of the catheter in place.

52A-54, an exemplary percutaneous renal fistula or urethral bypass catheter 7010 will be discussed. However, it should be understood that any of the catheters discussed herein can be used in a similar manner as described below. The exemplary urethral bypass catheter 7010 is configured to be deployed within a patient's urinary tract 7100 (shown in FIGS. 54, 55, and 57A-57E). Catheter 7010 includes elongated tube 7018 extending from proximal end 7020 to distal end 7022 . An extension tube 7018 is configured to pass into the patient's abdomen through a percutaneous opening or access site 7110 (shown in FIG. 54), and/or a distal portion 7014 comprising a retention portion 7016 configured to be deployed within the bladder. Percutaneous access site 7110 can be formed in a conventional manner, such as by inserting the tip of a needle through the skin and into the abdomen.

Tubing 7018 may be made of polyurethane, polyvinyl chloride, polytetrafluoroethylene (PTFE), latex, silicone-coated latex, silicone, polyglycolide or poly(glycolic acid) (PGA), polylactic acid (PLA), poly(lactic- co-glycolic acid), polyhydroxyalkanoic acid, polycaprolactone, and/or poly(propylene fumarate), and/or may consist of one or more biocompatible polymers. Portions of extension tube 18 may also be composed of and/or impregnated with metallic materials such as copper, silver, gold, nickel-titanium alloys, stainless steel, and/or titanium. The extension tube 7018 should be of sufficient length to extend from the renal pelvis 7112 through the kidney and percutaneous access site to an external fluid collection vessel. The tubing 7018 size can range from about 1 Fr to about 9 Fr (French catheter scale) or about 2 Fr to 8 Fr, or can be about 4 Fr. In some embodiments, tube 18 has an outer diameter ranging from about 0.33 mm to about 3.0 mm, or from about 0.66 mm to 2.33 mm, or from about 1.0 mm to 2.0 mm, and a diameter of about 0.165 mm. and inner diameters ranging from to about 2.40 mm, or from about 0.33 mm to 2.0 mm, or from about 0.66 mm to about 1.66 mm. In one example, tube 7018 is 6 Fr and has an outer diameter of 2.0±0.1 mm. The length of tube 7018 can range from about 30 cm to about 120 cm, depending on the patient's age (eg, pediatric or adult) and size.

The retention portion 7016 of the bypass catheter 7010 can be integrally formed with the distal portion 7014 of the catheter 7010 or a separate portion mounted to the distal end 7022 of the extension tube 7018 by conventional fasteners or adhesives. can be a structure. A number of exemplary retention portions 7016 suitable for retaining the distal end 7022 of the elongated tube 7018 within the renal pelvis 7112 are provided in the previous exemplary embodiment of the ureteral catheter 7010 . For example, the retaining portion 7016, comprising one or more of coils, funnels, cages, balloons, and/or sponges, can be adapted for use with the bypass catheter 7010. In some cases, such a retaining portion 7016 may, for example, be inverted by inverting the retaining portion 7016 and taking into account the fact that the urethral bypass catheter 7010 enters the renal pelvis 7112 through the kidney 7102 rather than through the ureter. It can be adapted for use with a urethral bypass catheter 7010.

Regardless of the embodiment chosen, the retention portion 7016 creates an outer perimeter or protected surface area that allows the urinary tract tissue to extend between the renal units of the kidney 7102 and the lumen of the elongated tube 7018. Prevents the column from shrinking or blocking. In some examples, such retention portions 7016 are inwardly directed, comprising one or more drainage openings, perforations, and/or ports 7026 for receiving fluids, such as urine, produced by the kidneys 7102. an outwardly facing side or protected surface area 7024 and an outwardly facing side or protected surface area 7028 that may be free or substantially free of exhaust ports 7026 . Desirably, the inwardly facing side or protected surface area 7024 and the outwardly facing side or protected surface area 7028 are such that when negative pressure is applied through the elongated tube 7018, urine flows through the one or more drainage ports 7026. It is configured to be drawn into the lumen of tube 7018 while preventing mucosal tissue, such as tissue of the ureter and/or renal pelvis 7112 , from significantly obstructing one or more exit ports 7026 . As in the ureteral catheters previously described, the size and spacing between the drainage ports 7026 achieve differential distribution of negative pressure within the renal pelvis 7112 and/or kidney 7102 as disclosed herein. can vary as In some examples, the one or more exhaust ports 7026 each have a diameter of about 0.0005 mm to about 2.0 mm, or about 0.05 mm to 1.5 mm, or about 0.5 mm to about 1.0 mm. have. In some examples, the exhaust port 7026 can be non-circular, from about 0.0002 mm ² to about 100 mm ² , or from about 0.002 mm ² to about 10 mm ² , or from about 0.2 mm ² to about 1.0 mm. It can have a surface area of ² . The exhaust ports 7026 can be equidistantly spaced along the axial length of the retaining portion 7016 . In other embodiments, exhaust ports 7026 closer to the distal end 7022 of the retaining portion 7016 increase fluid flow through the more distal exhaust ports 7026 compared to embodiments in which the ports 7026 are evenly spaced. may be spaced more closely together so as to increase the

A proximal portion 7012 of the catheter 7010 generally extends from the patient's kidney 7102 through a percutaneous access site 7110 . The proximal portion 7012 of the catheter 7010 is free or substantially free of perforations, openings, or exit ports 7026 to avoid drawing fluid from the peritoneal cavity into the elongated tube 7018 . Also, the proximal end 7020 of the proximal portion 7012 can be configured to connect to a fluid collection reservoir and/or a pump, as shown in FIG.

Exemplary Retention Portion As discussed above, the retention portion 7016 can be any structure suitable for maintaining the distal end 7022 of the elongated tube 7018 at the desired location within the urinary tract 7100 . For example, the fully sized retaining portion 7016 can have an axial length L1 ranging from about 5 mm to about 100 mm, or from 20 mm to 80 mm, or about 50 mm.

In some examples, the retention portion 7016 is configured to anchor and retain the retention portion 7016 within the renal pelvis 7112 and/or kidney 7102 from a retracted state when the catheter 7010 is inserted or removed from the patient. It has an expandable structure that transitions to an expanded or expanded state. To adequately retain the catheter 7010 at the desired location within the urinary tract 7100, in some embodiments, the retaining portion 7016 is positioned between the kidney 7102 and the proximal end 7020 of the catheter 7010 when deployed. It defines a three-dimensional shape 7032 (shown in FIG. 53) that is sized and positioned to maintain patency of the flowing fluid column. Further, desirably at least a portion of the fluid produced by kidney 7102 flows through retention portion 7016 and tube 7018 rather than through the ureter. The area of a two-dimensional slice 7034 (shown in FIG. 53) of the three-dimensional shape 7032 defined by the unfolded expandable retaining portion 7016 in a plane transverse to the central axis A of the expandable retaining portion 7016 is the expandable retention The portion 7016 can taper toward the distal end 7022 to give the retaining portion 7016 a pyramidal or inverted conical shape. In some examples, the maximum cross-sectional area of the three-dimensional shape 7032 defined by the deployed expandable retaining portion 7016 in a plane transverse to the central axis A of the expandable retaining portion 7016 is less than or equal to about 500 mm ² . Equal to or less than or equal to about 350 mm ² or between 100 mm ² and 500 mm ² or between 200 mm ² and 350 mm ² .

In some examples, the retaining portion 7016 comprises a coiled retaining portion comprising a reverse helical coil. The coiled retention portion 7016 is similar to the ureteral catheter retention described in connection with FIGS. 8A-9E, except that the coil orientation is reversed as the retention portion 7016 is inserted through the kidney and into the renal pelvis. Similar to part. The coiled retaining portion 7016 is such that the outer perimeter or outer region of the helical coils 7036, 7038, 7040 contacts and supports the tissue of the kidney 7102 and/or the renal pelvis 7112, and the inward direction of the helical coils 7036, 7038, 7040. a plurality of helical coils 7036, 7038, 7040 arranged to prevent occlusion or obstruction of the protected drain hole, port 7026, or perforation positioned within the side or protected surface area facing the can be done.

Coiled retaining portion 7016 includes at least a first coil 7036 having a first diameter D1 (see FIG. 52B), at least a second coil 7038 having a second diameter D2, and a third diameter D3. and at least a third coil 7040 having. The diameter D3 of the distal-most or third coil 7040 can be smaller than the diameter of either the first coil 7036 or the second coil 7038 so that the retaining portion 7016 fits within the renal pelvis 7112 . Thus, the diameter of coils 7036, 7038, 7040 and/or the step distance or height between adjacent coils 7036, 7038, 7040 may vary in a regular or irregular manner. In some examples, the plurality of coils 7036, 7038, 7040 can form a tapered or inverted pyramid shape with D1>D2>D3. In some examples, the coiled retaining portion 7016 can comprise a plurality of similarly sized coils, or, for example, a plurality of proximal similarly sized coils and a plurality of coils. and a distal-most coil having a smaller diameter than the other coils.

The diameters of the coils 7036, 7038, 7040 and the step distance or height between adjacent coils are selected such that the retaining portion 7016 remains within the renal pelvis and/or kidney for the desired period of time. In particular, the coiled retention portion 7016 desirably remains within the renal pelvis 7112 and does not pass either into the urethra or back into the kidney 7102 until the catheter 7010 is ready to be removed. , is sufficiently large. For example, outer diameter D1 of proximal-most or first coil 7036 can range from about 10 mm to 30 mm, or from about 15 mm to 25 mm, or about 20 mm. The second coil 38 can have a diameter of about 5 mm to 25 mm, or about 10 mm to 20 mm, or can be about 15 mm. The distal-most or third coil 40 can have a diameter D3 ranging from about 1 mm to 20 mm, or from about 5 mm to 15 mm, or can be about 10 mm.

Additional Exemplary Retaining Portions Another example of a ureteral catheter 7410 configured for percutaneous insertion into a patient's renal pelvis is shown in FIGS. 58A and 58B. As in the previous embodiment, the ureteral catheter 7410 is formed from an elongated tube 7418 and includes a proximal portion 7412 and a distal portion 7414 with a retention portion 7416 . Retention portion 7416 is a coiled retention portion comprising a plurality of coils wrapped around a generally linear or straight section or portion 7430 of extension tube 7418 .

Coiled retention portion 416 further comprises a distal-most coil 7432 formed from approximately a 90-180 degree bend 7434 at the distal end of a straight segment or portion 7430 of retention portion 7416 . The retaining portion 7416 further comprises one or more additional coils such as a second or central coil 7436 and a third or proximal coil 7438 wrapped around the straight portion 7430 of the tube 7418 . Extension tube 7418 further comprises distal end 7440 following proximal-most coil 7438 . The distal end 7440 can be closed or open to receive urine from the patient's urinary tract.

As in the previous embodiment, the size and orientation of coils 7432, 7436, 7438 are selected such that retention portion 7416 remains within the renal pelvis and does not pass into the ureter or retract back into the kidney. be done. For example, the largest or most proximal coil 7438 can be about 10 mm to 30 mm in diameter, or about 15 mm to 25 mm in diameter, or about 20 mm in diameter. Coils 7436 and 7438 can have a smaller diameter, for example, 5 mm to 25 mm, or about 10 mm to 20 mm, or about 15 mm. As in the previous example, the coiled retaining portion 7416 can have a tapered appearance with the coils 7432, 7436, 7438 becoming progressively narrower, giving the retaining portion 7416 an inverted pyramidal or inverted conical appearance. .

Also, as in the previous embodiment, the retaining portion 7416 further comprises an opening or exit port 7442 positioned on the radially inward side or protected surface area of the coiled retaining portion 7416 . Coils 7432, 7436, 7438 extend around the straight portion 7430 to prevent tissue of the renal pelvis and/or kidney from contacting the straight portion 7430 through openings or drain ports 7442 (shown in FIG. 54B). ) can also be positioned on the straight portion 7430 of the retaining portion 7416 . As in the previous example, the retention portion 7416 is inserted through the kidney and renal pelvis in a linear orientation over the guidewire. When the guidewire is removed, retention portion 7416 adopts a coiled or deployed configuration.

Urine Collection Systems with Percutaneous Catheters Urethral bypass catheters 7010, 7410 can be used in conjunction with systems for inducing negative pressure within a portion of the urinary tract 7100 of a patient. As shown in FIG. 55, an exemplary system 7200 comprises a urethral bypass catheter 7010 deployed within an individual renal pelvis 7112 of each individual kidney 7102 of a patient. A proximal end 7020 of catheter 7010 is connected directly or indirectly to pump 7210 . For example, the proximal end 7020 of catheter 7010 can be connected to the fluid inflow port of rigid fluid collection container 7212 . A pump 7210 can be connected to another port of the fluid collection container 7212 to induce a negative pressure within the fluid collection container 7212 and catheter 7010 connected thereto. The pump 7210 can be similar to the pumps in the previously described embodiments, and can be specifically configured to deliver a gentle negative pressure to the patient's urinary tract 7100 . Pump 7210 can be an external pump. In other examples, the pump 7210 may be, for example, a pump as described in Orr et al. can be an indwelling pump as described in PCT Application No. PCT/IB2018/056444. Generally, the negative pressure applied is a moderate negative pressure, such as a negative pressure of less than 50 mmHg. In other examples, the negative pressure can be from 2 mmHg to 100 mmHg or more, depending on the therapeutic needs of a particular patient. Pump 7210 desirably has a sensitivity of 10 mmHg or less.

In some examples, the system 7200 further comprises a bladder catheter 7216 that is deployed within the patient's bladder 7104 . Bladder catheter 7216 can be any suitable bladder catheter as described in the previous examples. Bladder catheter 7216 comprises elongated tube 7218 with proximal portion 7220 extending from the patient through urethra 7106 . A proximal end 7222 of the proximal portion 7220 of the bladder catheter 7216 can be connected to the fluid collection reservoir 7212 . In other examples, the bladder catheter 7216 can be connected to a separate fluid collection container 7224 that is not connected to the pump 7210 for inducing negative pressure. Fluid may then pass from the patient's bladder 7104 through the bladder catheter 7216 by gravity.

In some examples, the system 7200 further comprises a controller 7214 electrically connected to the pump 7210 configured to operate the pump 7210 and to control pump operating parameters. As in previous examples, controller 7214 may be the microprocessor of pump 7210 or a separate electronic device configured to provide operating instructions and/or operating parameters for pump 7210 . For example, controller 7214 can be associated with a computer, laptop, tablet, smart phone, or similar electronic device.

The system can further comprise one or more physiological sensors 7226 associated with the patient, fluid collection container 7212, or catheter 710,7216. Physiological sensor 7226 can be configured to provide information to controller 7214 representative of at least one physical parameter of the patient. In that case, the controller 7214 can be configured to activate or deactivate operation of the pump based on at least one physical parameter.

Deployment Method Having described aspects of the urethral bypass catheter 7010 and system 7200 for applying negative pressure to a patient, a method for insertion and/or deployment of the urethral bypass catheter will now relate to the flowchart of FIG. will be explained. Schematic diagrams showing different aspects of catheter deployment methods are shown in FIGS. 57A-57E. First, at box 7510, needle 7312 (shown in FIGS. 57A-57C) of cone tip catheter 7310 (shown in FIGS. 57A-57E) is inserted into the patient's abdominal region, thereby providing percutaneous generate a target access site. Catheter 7310 and needle 7312 should be of sufficient size to allow passage of a urethral bypass catheter through catheter 7310 . For example, the catheter 7310 can be about 3 Fr to about 10 Fr (French catheter scale), or about 5 Fr to about 8 Fr, or about 6 Fr. In some examples, the catheter 7310 can have an outer diameter ranging from about 0.5 mm to about 4 mm and an inner diameter ranging from about 0.2 mm to about 3.5 mm. The needle 7312 can be about 10-30 gauge, or about 20-25 gauge, and can have an outer diameter of 0.3 mm-3.5 mm, or about 0.5 mm-1.0 mm. Needle 7312 may be of any suitable length, such as 10 mm to 50 mm or about 30 mm.

Once needle 7312 is inserted through the patient's skin at 7512 , needle 7312 is advanced through the abdominal cavity and into kidney 7102 . At 7514, needle 7312 is advanced through kidney 7102 and into renal pelvis 7112, as shown in FIG. 57B. Once the needle 7312 is advanced to the renal pelvis 7112 at box 7516, a guidewire 7314 can be advanced through the needle 7312 to the renal pelvis 7112, as shown in FIG. 57C. Once guidewire 7314 is in place, needle 7312 can be retracted back through catheter 7310 . Next, at 7518, the extension tube 7318 of the catheter 7310 is inserted through the percutaneous access site into the patient's abdominal cavity and advanced over the guidewire 7314 and/or needle 7312 to the renal pelvis, as shown in FIG. 57D. can At 7520, once the distal end 7320 of the extension tube 7318 and the retention portion 7322 reach the renal pelvis, the retention portion 7322 can transition from its retracted state to its expanded or deployed state, as shown in FIG. 57E. Desirably, when deployed in the renal pelvis 7112, the retaining portion 7322 allows fluid flow into a lumen extending from the kidney 7102 through at least a portion of the elongated tube 7318, as described herein. Maintain patency.

In some examples, deploying the retaining portion 7322 can include retracting the outer tube or sheath proximally away from the retaining portion 7322 . Once the outer tube or sheath is removed, the retaining portion 7322 will automatically expand and return to its unconstrained shape. In other embodiments, such as when retaining portion 7322 comprises a coiled retaining portion, retracting guidewire 7314 causes retaining portion 7322 to adopt a coiled or deployed configuration. Deploying the retention portion can also include, for example, inflating a balloon or releasing a cage-like structure to protect the distal end of extension tube 7318 .

In some examples, as shown in box 7522, negative pressure is applied by directly or indirectly attaching the proximal end of extension tube 7318 to a fluid pump and activating the pump to generate negative pressure. It can be applied to the renal pelvis. For example, negative pressure can be applied continuously for a predetermined period of time. In other embodiments, the negative pressure can be applied as pressure pulses provided for short durations at predetermined intervals. In some examples, the pump can alternate between providing negative and positive pressure. It is believed that such alternating pressure therapy may also stimulate the kidneys resulting in increased urine production. In other embodiments, the negative pressure results from a pressure distribution or pressure gradient induced in tube 7318, but is extended without the use of a pump or negative pressure source, as described in more detail above. It may be delivered to the renal pelvis through tube 7318 . For example, a negative pressure sufficient to draw fluid, such as urine, into tube 7318 may be generated within the distal portion of tube 7318 in response to fluid flow through tube 7318 due to gravity. While not intending to be bound by theory, it is believed that the suction force generated depends on the vertical distance between the retention portion of the catheter and the proximal end of the catheter. Thus, the negative pressure generated can be increased by increasing the vertical distance between the retention portion of the deployed catheter and the fluid collection reservoir and/or proximal end of the catheter.

Exemplary Treatment Methods for Removing Excess Fluid Steps for removing excess fluid from a patient using the devices and systems described herein are illustrated in FIG. As shown in FIG. 49, the method of treatment includes inserting a urinary catheter, such as a ureteral stent or a ureteral catheter, into the patient's urine such that urine flows from the ureter and/or kidney, as shown in box 910 . Deploying within a duct and/or kidney. The catheter may be placed to avoid obstructing the ureters and/or kidneys. 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, a ureteral stent or ureteral catheter may be positioned within each of the patient's kidneys. In other examples, a 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, a ureteral catheter can comprise a tube defining a drainage lumen comprising a helical retention portion and a plurality of drainage ports. In other examples, the catheter can include a funnel-shaped fluid collection and retention portion or pigtail coil. Alternatively, a ureteral stent, for example with pigtail coils, can be deployed.

As indicated in box 912, the method further includes applying negative pressure to at least one of the bladder, ureter, and/or kidney through the bladder catheter to induce or induce fluid or urine production within the kidney. facilitating and extracting 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 embodiments, patient status may be monitored to determine when adequate therapy has been provided. For example, as indicated at box 914, the method may further include monitoring the patient to determine 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 hematocrit values. In other embodiments, blood samples may be taken periodically to measure hematocrit directly. In some examples, the concentration and/or volume of urine exiting the body through the bladder catheter may also be monitored to determine the rate at which urine is being produced by the kidneys. Similarly, voided urine may also be monitored to determine protein concentration and/or creatinine clearance rate for the patient. Reduced creatinine and protein concentrations in urine may indicate overdilution and/or decreased renal function. The measured values can be compared to predetermined thresholds to assess whether negative pressure therapy improves patient 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 other examples, patient weight may be measured and compared to dry weight as described herein. A measured change in patient weight demonstrates that fluid is being removed from the body. A return to dry weight therefore indicates that hemodilution is being adequately controlled and that the patient is not overdiluted.

As indicated in box 916, the user may cause the pump to stop providing negative pressure therapy upon identification of a positive result. Similarly, patient blood parameters may be monitored to assess the effectiveness of negative pressure being applied to the patient's kidneys. For example, a capacitance or analyte sensor may be placed in fluid communication with tubing of the extracorporeal blood management system. Sensors may be used to measure information indicative of blood protein, oxygen, creatinine, and/or hematocrit levels. Measured blood parameter values may be continuously or periodically measured and compared to various thresholds or clinically acceptable values. Negative pressure may continue to be applied to the patient's bladder, kidney, or ureter until the measured parameter value is within a clinically acceptable range. Once the measured value is within a threshold or clinically acceptable range, the application of negative pressure may cease, as indicated by box 916 .

In some embodiments, methods are 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 resuscitation infusion procedures such as coronary artery graft bypass surgery by removing excess fluid from the patient. During resuscitation infusion, solutions such as saline and/or starch solutions are introduced into the patient's bloodstream by a suitable fluid delivery process such as intravenous infusion. For example, in some surgical procedures, a patient may be supplied with a normal fluid intake 5-10 times a day. Fluid replacement or resuscitation fluids may be provided to replace fluids lost through sweating, bleeding, dehydration, and similar processes. For surgical procedures such as coronary artery graft bypass, resuscitation fluids are provided to help maintain the patient's fluid balance and blood pressure within appropriate rates. Acute kidney injury (AKI) is a known complication of coronary artery graft bypass surgery. AKI is associated with prolonged hospitalization and increased morbidity and mortality, even in patients who do not progress to renal failure. Kim, et al. , Relationship between a perioperative intravenous fluid administration strategy and acute kidney injury following off-pump coronary artery bypass surgery study: an observatory
See 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 block natural fluid management processes. Appropriate monitoring and control of renal function may therefore produce improved outcomes, particularly reducing postoperative cases of AKI.

A method of treating a patient to remove excess fluid is illustrated in FIG. As shown in box 1010, the method includes placing a ureteral stent or catheter into the patient's urine such that flow of urine from the ureter and/or kidney is not blocked by obstruction of the ureter and/or kidney. Deploying within a duct and/or kidney. For example, the distal end of the ureteral stent or fluid collecting 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 can comprise one or more of the ureteral catheters described herein. For example, a catheter can comprise a tube defining a drainage lumen and comprising a helical retaining portion and a plurality of drainage ports. In other examples, the catheter can include a pigtail coil.

As shown in box 1012, a bladder catheter can be deployed within the patient's bladder. For example, a bladder catheter may be positioned to at least partially seal the urethral opening and prevent passage of urine through the urethra from the body. A bladder catheter, for example, can include an anchor to maintain the distal end of the catheter within the bladder. As described herein, other arrangements such as coils and helices, funnels, etc. may be used to obtain proper positioning of the bladder catheter. Bladder catheters are designed to collect not only fluids that have entered the patient's bladder prior to placement of the ureteral catheter, but also fluids collected from the ureters, ureteral stents, and/or ureteral catheters during treatment. can be configured to The bladder catheter may also collect urine that flows over the fluid collection portion of the ureteral catheter and enters the bladder. In some examples, the proximal portion of the ureteral catheter may be positioned within the drainage lumen of the bladder catheter. Similarly, a bladder catheter may be advanced into the bladder using the same guidewire used to position the ureteral catheter. In some examples, negative pressure may be provided to the bladder through the drainage lumen of the bladder catheter. In other examples, negative pressure may be applied to the bladder catheter only. The ureteral catheter then drains into the bladder by gravity.

Following deployment of the ureteral stent and/or ureteral catheter and bladder catheter, negative pressure is applied through the bladder catheter to the bladder, ureters, and/or kidneys, as shown in box 1014 . For example, negative pressure can be applied for a period of time sufficient to extract urine containing some of the fluids provided to the patient during a resuscitation infusion procedure. As described herein, negative pressure can be provided by an external pump connected to the proximal end or port of the bladder catheter. The pump can be operated continuously or periodically, depending on the patient's therapeutic requirements. In some cases, the pump may alternate between applying negative pressure and applying 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 embodiments, patient status may be monitored to determine when a sufficient amount of fluid has been drawn from the patient. For example, as shown in box 1016, fluid discharged from the body may be collected and the total volume of fluid obtained may be monitored. The pump can then continue to operate until a predetermined volume of fluid has been collected from the ureteral and/or bladder catheter. The predetermined fluid volume may be based, for example, on the volume of fluid provided to the patient prior to and during a surgical procedure. As indicated by box 1018, application of negative pressure to the bladder, ureters, and/or kidneys is discontinued when the total volume of fluid collected exceeds a predetermined fluid volume.

In other examples, operation of the pump can be determined based on a measured physiological parameter of the patient, such as 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 capacitive sensor, an analyte sensor, an optical sensor, or similar device configured to measure urine analyte concentration. Similarly, as indicated in box 1022, the patient's blood creatinine or hematocrit level may be analyzed based on information obtained from the patient monitoring sensors discussed hereinabove. For example, a capacitive sensor may be installed within an existing extracorporeal blood system. Information obtained by the capacitive 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 ureters and/or kidneys until a measured value within a therapeutically acceptable range is obtained. Once a therapeutically acceptable value is obtained, application of negative pressure may be discontinued, as indicated in box 1018 .

In another example, as indicated in box 2024, patient weight may be measured to assess whether fluid is being removed from the patient by negative pressure therapy. For example, the patient's measured body weight (including fluids introduced during a resuscitation infusion procedure) can be compared to the patient's dry weight. As used herein, dry weight is defined as the normal weight measured when the patient is not overdiluted. For example, comfortably breathing patients who do not suffer from one or more of the following: elevated blood pressure, lightheadedness or muscle cramps, swelling around the legs, feet, arms, hands, or eyes Most likely it does not have fluid. Weight measured when the patient is not suffering from such symptoms may be dry weight. Patient weight can be measured periodically until the measured weight approaches the dry weight. As indicated by box 1018, when the measured body weight is approached (eg, within 5%-10% of dry body weight), the application of negative pressure can be stopped.

The foregoing details of treatment using the system of the present invention can be used to treat various medical conditions that may benefit from increased urine or fluid output or removal. For example, to preserve renal function through the application of negative pressure, reduce interstitial pressure within the renal tubules of the medullary region, facilitate voiding, and prevent venous congestion-induced renal unit hypoxia within the renal medulla. A method is provided. The method includes the steps of deploying a ureteral stent or ureteral catheter into the patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder; Deploying into the bladder, the bladder catheter having a distal end and a proximal end configured to be positioned within the patient's bladder and a drainage lumen portion extending therebetween. , a sidewall, 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 to remove fluid from the patient's urinary tract. step.

In another embodiment, a method is provided for treatment of acute renal injury due to venous stasis. The method comprises the steps of deploying a ureteral stent or ureteral catheter into the patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder; Deploying into the bladder, the bladder catheter having a distal end and a proximal end configured to be positioned within the patient's bladder and a drainage lumen portion extending therebetween. a side wall; and applying a negative pressure to the proximal end of the catheter to induce the negative pressure within a portion of the patient's urinary tract for a predetermined period of time to remove fluid from the patient's urinary tract. , thereby reducing venous congestion in the kidney and treating acute renal 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 intrarenal venous congestion. The method includes the steps of deploying a ureteral stent or ureteral catheter into the patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder; Deploying into the bladder, the bladder catheter having a distal end and a proximal end configured to be positioned within the patient's bladder and a drainage lumen portion extending therebetween. a side wall; and applying a negative pressure to the proximal end of the catheter to induce the negative pressure within a portion of the patient's urinary tract for a predetermined period of time to remove fluid from the patient's urinary tract. , treating fluid overload in NYHA Class III and/or Class IV heart failure.

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

In some examples, 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 comprises a ureteral stent or catheter with a drainage channel for facilitating fluid flow from the ureter and/or kidney through the drainage channel of the ureteral stent or catheter and toward the patient's bladder; A pump comprising a controller configured to induce pressure within at least one of a patient's ureter, kidney, or bladder and draw urine through a drainage lumen of a catheter deployed within the patient's bladder. and In some examples, the kit further comprises at least one bladder catheter. In some embodiments, the kit further performs one or more of the following: inserting/deploying a ureteral stent and/or ureteral catheter; inserting/deploying a bladder catheter; and operating a pump. and to draw urine through the drainage lumen of a bladder catheter deployed in the patient's bladder.

In some examples, another kit is a plurality of disposable bladder catheters, each bladder catheter having a proximal end, a distal end configured to be positioned within a patient's bladder, and a distal end configured to be positioned within a patient's bladder. and a sidewall extending radially outward from a portion of the distal end of the evacuation lumen portion, the retention portion having a diameter greater than the diameter of the evacuation lumen portion. a plurality of disposable bladder catheters, comprising: a retention portion configured to extend into a deployed position; instructions for inserting/deploying the bladder catheters; and instructions to operate the pump and draw urine through the drainage lumen of the bladder catheter, for example by applying a negative pressure to the proximal end of the bladder catheter.

In some embodiments, a kit is provided, the kit comprising a plurality of disposable bladder catheters, each bladder catheter comprising (a) a proximal portion and (b) a distal portion, one protected vents, ports, or perforations to prevent mucosal tissue from occluding one or more of the protected vents, ports, or perforations in response to application of negative pressure through the catheter; a plurality of disposable bladder catheters comprising: a distal portion comprising a retaining portion configured to establish an outer perimeter or protective surface area to establish an outer perimeter or protective surface area for the bladder catheter; instructions for deploying the bladder catheter; and instructions for connecting the end 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 within the renal pelvis of domestic pigs was performed for the purpose of evaluating the effect of negative pressure therapy on intrarenal renal stasis. The purpose of these studies was to demonstrate whether negative pressure delivered into the renal pelvis significantly increases voiding in a porcine model of renal stasis. In Example 1, a pediatric Fogarty catheter, commonly used in embolectomy or bronchoscopy applications, was used in a porcine model solely for proof of principle of inducing negative pressure in the renal pelvis. The Fogarty catheter is not suggested for human use in a clinical setting to avoid injury to urinary tract tissue. In Example 2, a ureteral catheter 112 was used, shown in FIGS. 2A and 2B and including a helical 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 intrarenal renal congestion. Pediatric Fogarty catheters 812, 814 were inserted into the renal pelvic regions 820, 821 of each kidney 802, 804 of four pigs 800, as shown in FIG. Catheters 812, 814 were deployed within the renal pelvis area by inflating the expandable balloon to a size sufficient to seal the renal pelvis and maintain the balloon's position within the renal pelvis. Catheters 812, 814 extend from the renal pelvis 802, 804 through the bladder 810 and urethra 816 to a fluid collection container external to the pig.

Voids of two animals were collected over 15 minute cycles to establish a baseline for voided volume and rate. Right kidney 802 and left kidney 804 voiding were measured individually and found to vary significantly. Creatinine clearance values were also determined.

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

One kidney of each animal 800 was untreated 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 for determining fluid levels. One kidney of each animal (the "treatment kidney 804") is connected to a ureteral catheter 814, in combination with a negative pressure source (e.g., a regulator designed to more precisely control small magnitude negative pressures). was treated with negative pressure from the therapy pump 818). Pump 818 was an Air Cadet Vacuum Pump manufactured by Cole-Parmer Instrument Company (model number EW-07530-85). A pump 818 was connected in series with the regulator. The regulator is from Airtrol Components Inc. V-800 Series Miniature Precision Vacuum Regulator-1/8 NPT Ports (model number V-800-10-W/K).

Pump 818 was actuated to induce negative pressure within the renal pelvis 820, 821 of the treated kidney according to the following protocol. First, the effect of negative pressure was investigated under normal conditions (eg, without inflating the IVC balloon). Four different pressure levels (-2, -10, -15, and -20 mmHg) were applied for 15 minutes each and the rate of urine produced and creatinine clearance was determined. Pressure levels were controlled and determined in regulators. Following the -20 mmHg therapy, the IVC balloon was inflated to increase pressure by 15-20 mmHg. The same four negative pressure levels were applied. Urinary output and creatinine clearance rates for the stagnant control kidney 802 and the treated kidney 804 were obtained. Animal 800 was held by partial occlusion of the IVC for 90 minutes. Treatment was provided for 60 minutes of a 90-minute stasis cycle.

Following collection of voiding 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, 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 micrograph images of sampled tissues were obtained at low (20x original magnification) and high (100x original magnification) magnification. Acquired images underwent histological evaluation. The purpose of the evaluation was to histologically examine the tissues and qualitatively characterize retention and tubular degeneration on the samples obtained.

Surface mapping analysis was also performed on acquired slides of kidney tissue. Specifically, samples were stained and analyzed to assess differences in tubule size for treated and untreated kidneys. Image processing techniques calculated the number and/or relative percentages of pixels with different coloration within the stained image. The calculated measurement data were used to determine the volume of different anatomical structures.

result
Urination and creatinine clearance
Urine output was highly variable. Three sources of variation in urine output were observed during the study. Inter-individual and hemodynamic variability were the expected sources of variability known in the art. A third source of variability in urination was identified in the experiments discussed herein, based on information and ideas believed to be previously unknown, namely contralateral intra-individual variability in urination. .

Baseline urine output was 0.79 ml/min for one kidney and 1.07 ml/min for the other kidney (eg, 26% difference). Urination 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 voided volume, the relative increase in treatment renal voiding compared to control renal voiding 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%

Therefore, the relative increase in therapeutic renal output was 180.6% compared to controls. The results show a greater reduction in urine production caused by stasis on the control side compared to the treated side. Presenting results as relative percentage differences in voiding controls for differences in voiding between kidneys.

Creatinine clearance measurements for baseline, retention, 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 treatment kidney (left kidney), it was determined that the control kidney had a uniformly dark brown color, which was compared to the treatment kidney. corresponding to more stasis in the control kidney. Qualitative evaluation of enlarged section images also focused on increased congestion in control kidneys compared to treated kidneys. Specifically, as shown in Table 1, treated kidneys exhibited lower levels of congestion and tubular degeneration compared to control kidneys. The following qualitative scale was used for evaluation of the slides obtained.

As shown in Table 1, the treated kidney (left kidney) exhibited only low-grade congestion and tubular degeneration. In contrast, the control kidney (right kidney) exhibited moderate 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 animal's left kidney (treated with negative pressure). Based on histological examination, a low degree of vascular congestion at the corticomedullary junction was identified as indicated by the arrow. As shown in Figure 48B, a single tubule (as identified by an asterisk) with a hyaline cast was identified.

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

Surface mapping analysis provided the following results. Treated kidneys were determined to have 1.5 times greater fluid volume in Bowman's space and 2 times greater fluid volume in the tubular lumen. Bowman's space and increased fluid volume within the tubular lumen correspond to increased urination. In addition, treated kidneys were determined to have 5-fold less blood volume in the capillaries compared to control kidneys. The increased volume within the treated kidney was associated with (1) a decrease in individual capillary size compared to the control and (2) an increase in the number of capillaries without visible red blood cells within the treated kidney compared to the control kidney, i.e., Resulting in an indicator of less congestion in the treated organ.

Summary These results showed that control kidneys had more tubules with more stasis and intraluminal hyaline casts, representing protein-rich intraluminal material compared to treated kidneys. indicates that Thus, treated kidneys exhibit a lower degree of loss of renal function. Without intending to be bound by theory, it is believed that as severe congestion develops within the kidney, organ hypoxemia follows. Hypoxemia interferes with oxidative phosphorylation (eg ATP production) within the organ. A loss of ATP and/or a decrease in ATP production blocks active transport of proteins and increases intraluminal protein content, which manifests as hyaline casts. The number of renal tubules with intraluminal hyaline casts correlates with the degree of loss of renal function. Therefore, the reduced number of renal tubules in the treated left kidney is considered physiologically significant. Without intending to be bound by theory, these results suggest that damage to the kidney is prevented or prevented by applying negative pressure to a ureteral catheter inserted into the renal pelvis to facilitate voiding. It is considered to indicate that it can be blocked.

(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 FIGS. 2A and 2B, was deployed within 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 is 54±2 cm long and does not include a distal retention portion. The retention portion was 16±2 mm long. As shown in catheter 112 in FIGS. 2A and 2B, the retention portion included two full coils and one proximal half-coil. The outer diameter of the complete coil indicated by line D1 in FIGS. 2A and 2B was 18±2 mm. The half coil diameter D2 was about 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 discharge openings was 0.83±0.01 mm. The distance between adjacent discharge openings 132, specifically the linear distance between discharge 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 each pig's external fluid collection container. Following placement of the ureteral catheter, a pressure sensor was placed within the IVC at a location distal to the renal vein to measure IVC pressure. Inflatable balloon catheters, specifically NuMED Inc. (Hopkinton, NY) PTS® percutaneous balloon catheter (30 mm diameter x 5 cm length) was dilated within the IVC at a location proximal to the renal vein. Thermodilution catheters, specifically Edwards Lifesciences Corp. (Irvine, CA) Swan-Ganz thermodilution pulmonary artery catheter was then placed in the pulmonary artery for the purpose of measuring cardiac output.

Initially, baseline voiding was measured over 30 minutes and blood and urine samples were collected for biochemical analysis. Following a 30 minute baseline cycle, 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 along with corresponding blood and urine analyzes over 30 minutes.

At the end of the stasis cycle, 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 number EW-07530-85). The pump was connected in series with the regulator. The regulator is from Airtrol Components Inc. V-800 Series Miniature Precision Vacuum Regulator-1/8NPT Ports (model number V-800-10-W/K). Pigs were observed as treatment was provided for 120 minutes. Blood and urine collections were performed every 30 minutes during the treatment cycle. 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) and two pigs (B, D) received negative pressure diuretic therapy. means that you did not receive

Following collection of voiding and creatinine clearance data over a 120 minute treatment cycle, animals were sacrificed and kidneys from each animal were macroscopically examined. Following macroscopic examination, tissue sections were obtained and examined, and magnified images of the sections were captured.

加えて、好中球ゼラチナーゼ結合性リポカリン（ＮＧＡＬ）値が、時間周期毎に取得された血清サンプルから測定され、腎臓傷害分子１（ＫＩＭ－１）値が、時間周期毎に取得された尿サンプルから測定された。取得された組織切片の精査から判定された定質的組織学的見解もまた、表２に含まれる。

Results Baseline, retention, and measurements collected during the treatment cycle are provided in Table 2. Specifically, micturition, serum creatinine, and urine creatinine measurements were obtained for each time period. These values allow the calculation of the measured creatinine clearance as follows.

Additionally, neutrophil gelatinase-binding lipocalin (NGAL) values were measured from serum samples obtained at each time period, and kidney injury molecule 1 (KIM-1) values were measured from urine samples obtained at each time period. measured from Also included in Table 2 are the qualitative histological findings determined from inspection of the tissue sections obtained.

Animal A: Animal weighed 50.6 kg, had a baseline voided volume of 3.01 ml/min, a 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 elevated compared to other animals studied. Stasis was associated with a 98% reduction in voided volume (0.06 ml/min) and a >99% reduction in CrCl (1.0 ml/min). Treatment with negative pressure applied through a ureteral catheter was associated with micturition and CrCl 17% and 12% of baseline values, respectively, and 9- and >10-fold stasis values, respectively. Levels of NGAL varied throughout the experiment, ranging from 68% of baseline during stasis to 258% of baseline after 90 minutes of therapy. The final value was 130% of baseline. Levels of KIM-1 increased to 68-fold, 52-fold, and 63-fold above baseline values over the last three collection cycles, respectively, before the first two 30-minute intervals after baseline assessment. 6- and 4-fold baseline over the time frame. Two-hour serum creatinine was 1.3 mg/dl. Histological examination revealed an overall stasis level of 2.4% as measured by blood volume within the capillary space. Histological examination also noted several tubules with intraluminal hyaline casts and some degree of tubular epithelial degeneration, found consistent with cellular damage.

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

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

Animal D: The animal weighed 38.2 kg, had a baseline micturition of 0.98 ml/min, a baseline serum creatinine of 1.0 mg/dl, and measured CrCl of 46.8 ml/min. rice field. Stasis was associated with a 75% reduction in voided 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. Levels of NGAL varied throughout the experiment, ranging from 127% of baseline during stasis to a final value of 209% of baseline. Levels of KIM-1 increased to 190-, 219-, and 201-fold over baseline values over the last three 30-minute cycles in the first two 30-minute time windows after baseline assessment. remained 1-2 times baseline over time. The 2-hour serum creatinine level was 1.7 mg/dl. Histological examination revealed that overall stasis levels were 2.44-fold greater than those observed in tissue samples for treated animals (A, C), and mean capillary size was observed in any of the treated animals. 2.33 times higher than the original. Histological evaluation also noted several tubules with intraluminal hyaline casts as well as tubular epithelial degeneration, showing substantial cellular damage.

Summary While not intending to be bound by theory, the collected data appear to support the hypothesis that venous stasis has a physiologically significant effect on renal function. Specifically, increased renal vein pressure was observed to reduce voiding by 75% to 98% within seconds. The association between elevations in biomarkers of tubular injury and histological damage is consistent with the extent to which venous stasis develops, both in terms of magnitude and duration of injury.

The data are also found to support the hypothesis that venous stasis reduces the filtration gradient within the medullary renal unit by altering interstitial pressure. The alterations are found to contribute directly to hypoxia and cell injury within the medullary renal unit. Although this model does not mimic the clinical condition of AKI, it does provide insight into mechanical sustained injury.

The data also appear to support the hypothesis that applying negative pressure to the renal pelvis through a ureteral catheter can increase voiding in a model of venous stasis. In particular, negative pressure therapy was associated with increased voiding and creatinine clearance, which may be clinically significant. A physiologically significant decrease in medullary capillary volume and a smaller increase in biomarkers of tubular injury were also observed. Thus, it can be seen that by increasing urine output and decreasing interstitial pressure within the medullary renal unit, negative pressure therapy can directly reduce congestion. Without intending to be bound by theory, it can be concluded that, by reducing congestion, negative pressure therapy reduces intrarenal hypoxia and its downstream effects in venous congestion-mediated AKI.

Experimental results are found to support the hypothesis that the degree of stasis, both in terms of pressure magnitude and duration, is related to the degree of observed cellular injury. Specifically, an association between reduced voiding and degree of histological damage was observed. For example, treated pig A, which had a 98% reduction in urination, suffered more injury than treated pig C, which had a 75% reduction in urination. As might be expected, control pig D, which suffered a 75% reduction in micturition without benefit from therapy over 2½ hours, exhibited the most histological damage. These observations are broadly consistent with human data demonstrating an increased risk of developing AKI with more venous congestion. For example, Legrand, M.; et al. , Association between systemic 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 within the renal pelvis of domestic pigs using a ureteral catheter was performed for the purpose of evaluating the effect of negative pressure therapy on blood hemodilution. The purpose of these studies was to demonstrate whether negative pressure delivered into the renal pelvis significantly increases voiding in a porcine model of resuscitation infusion.

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 a control (#6566). Following placement of the ureteral catheter, animals were transferred to a bed and monitored for 24 hours.

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

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

Summary Without intending to be bound by theory, the data collected support the hypothesis that volume overload induces clinically significant effects on renal function and, consequently, hemodilution. Conceivable. In particular, it has been observed that administration of large amounts of intravenous saline cannot be effectively cleared even by healthy kidneys. The resulting fluid accumulation leads to hemodilution. The data also show that applying negative pressure diuretic therapy to volume-overweight animals using a ureteral catheter increases voiding, improves net fluid balance, and reduces the effect of resuscitation fluids on the development of hemodilution. This seems to support the hypothesis that it is possible to

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

Claims (1)

The inventions described herein.

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