WO2007009496A1 - Hemodialyse ou hemodiafiltration differentielle - Google Patents

Hemodialyse ou hemodiafiltration differentielle Download PDF

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Publication number
WO2007009496A1
WO2007009496A1 PCT/EP2005/053580 EP2005053580W WO2007009496A1 WO 2007009496 A1 WO2007009496 A1 WO 2007009496A1 EP 2005053580 W EP2005053580 W EP 2005053580W WO 2007009496 A1 WO2007009496 A1 WO 2007009496A1
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Prior art keywords
blood
dialyser
patient
header
inflow
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PCT/EP2005/053580
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English (en)
Inventor
Arezki Mahiout, Ph. D.
Original Assignee
Mahiout Arezki Ph D
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Priority to PCT/EP2005/053580 priority Critical patent/WO2007009496A1/fr
Publication of WO2007009496A1 publication Critical patent/WO2007009496A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
    • B01D63/02—Hollow fibre modules
    • B01D63/033—Specific distribution of fibres within one potting or tube-sheet
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3403—Regulation parameters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3403—Regulation parameters
    • A61M1/341—Regulation parameters by measuring the filtrate rate or volume
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3601—Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit
    • A61M1/3603—Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit in the same direction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3607—Regulation parameters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3331—Pressure; Flow
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3331—Pressure; Flow
    • A61M2205/3334—Measuring or controlling the flow rate
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2313/00—Details relating to membrane modules or apparatus
    • B01D2313/10—Specific supply elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2321/00—Details relating to membrane cleaning, regeneration, sterilization or to the prevention of fouling
    • B01D2321/20—By influencing the flow
    • B01D2321/2008—By influencing the flow statically

Definitions

  • the present invention relates to a dialysis apparatus for hemodialysis or for hemodiafil- tration comprising a dialysate flow path, an extracorporeal blood flow path and a dialyser device and a method for hemodyalysis or hemodiafiltration.
  • Extracorporeal blood treatment such as hemodialysis is a process used for the removal of an excess of water, electrolytes and toxins in end stage renal disease.
  • the treatment essentially makes use of an extracorporeal apparatus, wherein via a shunt grafted in the patient, arterial blood flows on one side of a semi-permeable membrane and a physiologic solution flows on the other side of the semi-permeable membrane inducing blood toxins to move from one side to the other. After the blood passage through the device, blood is returned via the grafted shunt to the patient vein system.
  • the blood detoxication is performed through driving forces such as diffusion for small molecules (up to 1000 MW) due to a trans-membrane concentration gradient, and such as convection of water, middle and large molecules toxins (> 1000 MW) due to a trans-membrane pressure.
  • dialyser devices are designed with a semi-permeable membrane in form of hollow fibres, with a bundle of fibres being encased in a cylinder tubular housing. The bundle is bounded at the two ends of the tubular housing and a screw cap manifold is used. Blood enters the device via the manifolds that are designed to optimize both blood velocity and pressure drops at all points in the manifold, thereby ensuring an even distribution of the blood in the fibre bundle.
  • Dialysers containing membranes with low permeability with a cut off below 5000 MW achieve only the removal of toxins by diffusion.
  • Dialysers of higher permeability membranes achieve toxin removals by diffusion combined with convection.
  • US 7,776,912 discloses a new configuration of the dialysate compartment to influence the dialysate resistance.
  • US 6,843,779 discloses the use of several dialyser devices in series.
  • US 2002/0053540 A1 discloses a design specially designed for hemodiafiltration. It involves a new dialyser design which relates to a dual stage filtration module, provides redundant sterile filtration and produces physiologic fluid for infusion.
  • US 6,641 ,731 discloses a new dialyser design having a low-stress transfer of blood from the connections to the fibre bundle.
  • the present invention relates to a novel apparatus and method for treating extracorporeal blood in uraemia patients.
  • the invention particularly discloses an apparatus and a method for proceeding patients ' blood resulting in an improvement of the performance of hemodialysis on the one hand and a reduction of the dialyser membrane surface area on the other hand. It is substantially based on a novel dialyser design combined with a novel blood operation method.
  • the concept relates to a blood reperfusion of the dialyser device, and the procedure occurs in a cyclic fashion. It works like the process of blood reperfusion of a single dialyser device, wherein the reperfusion is cycled, for which frequency is the number of reperfusions that take place per minute.
  • the concept is providing a blood treatment in a more intensive extent than the standard treatment, while improving both the diffusion performances of bound and unbound blood toxins and improving the convection performance of larger molecules.
  • the term "diffential haemodialysis procedure" can used to refer to a procedure that is conversing the performance of the treatment when compared to standard treatments.
  • the present invention provides the advantage of reducing the size of the dialyser membrane if compared with standard dimensions of membranes used in standard dialysis, while also conserving the performance needed.
  • the present invention represents a novel alternative while converting diffusion transport to a higher degree.
  • it also represents an alternative to standard hemodiafiltration while improving both diffusion and convection transport.
  • the present invention discloses a new apparatus and method in the blood processing treatment.
  • the present invention relates to a technique, which is substantial in increasing the removal of free and of albumin bound toxins on one hand and in decreasing the dimension of the dialyser device on the other hand. Decreasing the membrane surface and increasing efficiency, therefore, may decrease costs and/or allow an optimal treatment for the patients.
  • the present invention discloses a new dialyser design and a method of operating the extracorporeal blood.
  • this is a concept of hemodialysis treatment which involves the process of a multiple blood reperfusion of a hemodialyser device, specified in this invention as "reperfusion cycles" of the blood through the dialyser, in comparison to a single perfusion as normally used by standard dialysis.
  • the inventive enables to use a small membrane surface area while achieving the performance of a dialyser with a larger membrane surface area.
  • the present invention relates to the amplification in the removal of toxin solutes including phosphate and of albumin bound toxins for which the physico-chemical property in their solubility in plasma is limited.
  • the present can be adapted for hemodialysis treatment as well as for hemodiafiltration, preferably in a pre-dilution mode.
  • an embodiment of an apparatus, which allows that the inflowing patient's blood perfuses the dialyser device during several cycles before entering the patient.
  • the technical concept of this embodiment is described by a combination of two primary pumps 101 and 102, which control the arterial blood inflow and the venous blood outflow blood of the patient described as primary flow, and one secondary blood pump 103 that controls the number of reperfusion cycles which circulate as shunt in relationship with the primary flow and which is defined as a secondary flow.
  • N (N+ 1) Q B (1) wherein Q B is the patient inflow blood flow rate, N is the number of reperfusions or the number of cycles N (N > 1) applied in the treatment, and N is a natural number.
  • C 1 is the concentration of a solute in the blood inlet
  • C 0n the concentration at the blood outlet after n cycles
  • K is the clearance
  • K 1 2 Q B ( (Ci + 1 *Co)/2 - C 01 VCi (3)
  • N n the final clearance of a solute is given by the formula by a recurrence calculation:
  • K n (n+1)Q B ( (Ci+ n*Con-i)/(n+1) - C on )/Ci (6) or
  • K n QB (Ci+ n*C on- i - (n+ 1 ). C on )/Ci (7)
  • the final clearance depends on the number of the reperfusion cycles. The higher the number of the reperfusion cycles is, the higher will be the clearance.
  • a configuration of blood pumps that allows the blood to flow through the device in a reperfusion-cycled fashion and to enter the patient by conserving the blood mass balance in time.
  • the first step is the control of the primary flow which is the patient blood inflow and blood outflow, thereby defined here in relation to the dialyser device.
  • the blood inflow is flowing from the patient and the blood outflow is flowing back to the patient.
  • the apparatus is processing with three pumps: For a primary flow, there are two pumps, the arterial pump and the venous pump.
  • the first pump connects the patient to the device and controls the patient's arterial flow rate
  • the second pump connects the device to the patient and controls the patient's venous blood flow rate.
  • the first pump 101 is connected to the dialyser device 104 at the inlet connection header cap and pumps the blood from the patient to the inlet connection of the dialyser device 104 at a flow rate of QB.
  • the second pump 102 is connected to the outlet connection of header cap and pumps blood from the outflow of the device to the patient at a flow rate Q B - UFR, wherein UFR is the ultrafiltration rate of the treatment.
  • the third blood pump 103 is pumping and controlling the reperfusion cycles. It is mounted in a bypass fashion to the primary flow, and is pumping the blood from the outlet part to the inlet part of the dialyser device 104.
  • a relationship is provided between Q B and Q c and the dialysate flow according to N, the number of reperfusion cycles. It is also pro- vided that for each reperfusion cycle, fresh dialysate should flow in a counter current fashion through the dialyser module. Such achievement is taking into account that the dialysate flow is at least equal to or higher as 2*(Q C + Q B ), which means twice the blood flowing trough the dialyser device 104.
  • the fresh counter-current flow keeps a maximum concentration gradient of uraemia toxins allowing for high diffusive clearance of soluble and albumin bound toxins, which is important for N > 1 for which the performances in the clearance are improved in this invention and for which also a high dialysate flow is needed.
  • a dialyser design adapted to the blood apparatus concept.
  • the dialyser includes as usual a cylindrical body having two ends and having an interior potting encasing a semi permeable membrane in form of a fibre bundle. Therefore, the module is especially characterized in that at the cylindrical blood connection header caps there are two connections for the blood inlet and two connections for the blood outlet. This characterisation is related to a design of the internal surface the connection cap header. Accordingly in the internal space of the first connection cap header located in the first end of cylinder fibre bundle and linked with the blood inflows, there is provided a double thin mixture chambers.
  • This cap head includes both the port of the patient blood inlet Q B and the port of the inflow reperfusion cycle blood Qc-
  • the two ports are directed in a tangential fashion to the end cylindrical cap header, in the way that both are orientated in the same direction.
  • the second connection cap head located at the other end of the cylinder fibre contains as usual a single thin cylindrical chamber but also includes two ports, one for the patient blood outlet Q B and the other port for the outflow reperfusion cycle blood pumped trough Qc- Similar to the first cap, both ports are also tangentially oriented to the internal surface of the cylindrical end cap.
  • the dialyser device includes a single cylindrical housing having a cylindrical hollow fibre bundle disposed therein, it also preferably includes a polyurethane potting material encasing the fibre bundle in each end of the cylindrical body which is closed at the ends with the described header caps.
  • the cylindrical housing is preferably made of a rigid and transparent synthetic material such as polycarbonate.
  • the fibre bundle consists of low permeable or high permeable membranes that are commercially available for the application of hemodialysis or hemodiafiltration. Due to a higher blood flow proceed in the device, the dialyser length is this invention is shorter as conventional the fibre bundle, whereas the diameter of the cylinder housing will be larger as usual.
  • the first header cap which is located at the blood inflow connections of the device, is composed of two spaces in communication with an orifice at the centre.
  • the form of these chambers is preferably designed like a helicoids internal surface or a helicoids-like surface.
  • This aspect allows an optimal mixture of both blood flows Q B and Qc in a first convergent chamber before entering the divergent second chamber resulting in a homogenous distribution of the mixed blood.
  • a surface has been experimentally optimized for minimal blood trauma even by high blood flow.
  • the two chambers are in communication trough an orifice located at the central point of a helicoids wall, which is located on the axis of the device cylinder.
  • the blood inflows pumped from Q B and from Q c enter the first space and thus mixed at the ratio given by the number of perfusion cycles N but by conserving a laminar flow characteristic although the flow pattern is circular. Thereafter, in the second compartment the mixed blood is distributed in a laminar flow characteristic and loosing the circular flow pattern to enter the fibres.
  • t and n are variable parameters, preferably t may vary between 1.0 and 10.0, and n may vary between 0.1 and 1.
  • a surface represents a helicoid with a helix as surface boundary along the z-axis, with two circles as boundary over the x-y surface.
  • the dialyser device of this invention has been adapted to operate with the blood treatment and vice versa.
  • the blood is guided from patient to the dialyser blood inflow connection via a bloodline.
  • the reperfusion cycling process is guiding a volume of blood through the second blood inflow connection, whereas in the starting conditions the first step or reperfusion medium is saline.
  • the method provides that blood passes through the dialyser at a flow rate that is higher as the flow rate of the patient incoming blood.
  • the method also provides that during the process of hemodialysis and of the reperfusion cycles through the dialyser device, the volume of the patient incoming blood part minus the ultrafiltrate volume is pumped back to the patient at the same time frequency as the patient incoming blood.
  • Figures 1a-b are schematic diagrams illustrating the blood flow in an apparatus according to preferred embodiments of the invention.
  • Figure 1c is a schematic cross-sectional view of a dialyser according to a preferred embodiment of the invention.
  • Figures 2a-c are different views of a cap header used in a dialyser as shown in Figure 1c;
  • Figure 2d shows a blood flow stream configuration in a 3-dimension scope from the top level of the cap header of Figure 2c;
  • Figures 3a-b show the dependence of the physical factor affecting blood trauma at the level of the hollow fibres (Figure 3a) and of the header cap (Figure 3b), represented by the wall shear ⁇ and the exposition time t, in dependence of the number N of cycles for a dialysis apparatus according to the present invention.
  • Figures 4-10 show the dependence of several clearance-characteristics on the number N of cycles for a dialysis apparatus according to the present invention.
  • Figure 1a illustrates according to a preferred embodiment of the invention the concept of a blood apparatus providing blood reperfusion cycles through a dialyser device 104 in a hemodialysis mode.
  • the blood reperfusion cycles are provided by an arrangement of blood pumps allowing blood to pass through the dialyser, to be pumped in a bypass fashion to pass again the same dialyser device for one or multiple cycles, and returning to the patient.
  • the combination of two primary blood pumps 101 and 102 controlling the arterial inflow and the venous outflow, QB, of the blood of the patient, and a reperfusion cycle blood pump 103 controlling the flow Qc, the latter being determined by the number of reperfusion cycles N via the formula Qc N Q B , with N being a natural number which may have a variation step of 0.1.
  • the two pumps 101 and 102 provide both inflow and outflow Q B during reperfusion cycle process of the device 104 and control the arterial- venous pressure gradient. Both Q B inflow and Q B outflow are synchronized; while inflow Q B is pumping the blood from the patient, outflow Q B is returning the blood to the patient.
  • the ultra filtration rate is taking into consideration the mass balance of the patient inflow and outflow blood circulation during the treatment.
  • the Qc blood pump 103 controls the number of reperfusion cycles N.
  • the dialysate system which is described trough the flow 105 and 106 should be related to the conventional state of the art of standard dialysis concept. However, the dialysate should be able to produce flow rates between 800 ml/min and 2000 ml/min.
  • Figure 1 b illustrates a blood system concept for an apparatus as previously described with reference to Figure 1a, which is providing the cycling of the blood through the dialyser 104, but for hemodiafiltration application.
  • Figure 1 b illustrates the blood system in a dialysis apparatus for hemodiafiltration mode that is characterised by four blood pumps. The system is similar to the previous description, with the difference that an infusion pump has been added for hemodiafiltration mode.
  • this embodiment includes an additional pump system 107, which controls the flow rate of infusion solution, in a pre-dilution hemodialfiltration mode.
  • Figure 1c illustrates a dialyser design in accordance with the present invention.
  • the device has been adapted to operate with the previous example of blood operating system. It is a dialyser including a cylindrical housing made of a rigid and transparent synthetic material such as a medical grade Polycarbonate. A housing is filled with a bundle of low permeable or high permeable fibres 205, which are commercially available for the application field of hemodialysis. The fibre bundle and the cylinder may vary between 12 and 21 cm, but in the present invention preferably between 12 and 17 cm according to the surface area.
  • a cap header 204 which is referred to as the arterial cap header has a cylindrical form and is mounted at the end of the cylinder containing the fibre bundle. As usually, the cap header is screwed and fixed with a glue composed as usual with the same polycarbonate chemistry.
  • An internal space 203 of the cap header 204 has the function of receiving the blood inflow 201 of the patient and the blood inflow 202 of the reperfusion cycles blood.
  • This space 203 is directly communicating with the interior of the fibres 205 and it is isolated from the external part of the fibre and from the housing cylinder by a potting 206 compound made of a thermoplastic poly- urethane.
  • the circular end of the potting is sealed with the internal space of the header cap with an O-ring 213.
  • Two blood inlet ports 201 and 202 are contained in the header cap and directed in a tangential of the circular internal part of the cap 204 for which detailed description is represented below.
  • a second header cap 212 that is mounted at the end of the fibre cylinder has been designed as usual through a cylinder.
  • Dialysate ports 207, 211 defined as Hansen port type are contained in the external part of the fibre cylinder as usual known in the art. According the known principle of a counter-current flow to the blood, port 211 is the dialysate inflow port and 207 is the dialysate outflow port. Both ports 207 and 211 are located as usual at the end of the fibre bundle.
  • Figure 2a, 2b, 2c, and 2d illustrate the shape of the preferred embodiment specifying the inner header as an internal surface of a helicoids function R(x,y)/R(z) in its general term.
  • Figure 2a illustrates the surface in the view of the y- axis, whereas the z-axis represents the longitudinal direction of the cylinder bundle and the x-axis represents the other horizontal axis of the cylinder bundle
  • Figure 2b illustrates the internal surface in a 3-dimensional scope
  • Figure 2c illustrates the surface from the view of the z-axis which the longitudinal view of the cylinder bundle;
  • the first space closed is specified as the convergent part, and it has the function of providing the mixing of both blood inflows having different concentrations of toxins.
  • Figure 2d illustrates the streamlines of the flow distribution.
  • Figure 2d shows a blood flow stream configuration in a 3-dimension scope from the top level the cap header of Figure 2c. The imaging was performed with the help of Doppler laser velocimetry measurement using a transparent Newton medium with a viscosity equal to a blood with a hemo- tocrit of 32%.
  • Another aspect of the invention seeks to provide no blood damage resulting in an increase of the blood shear rate at the level of the connections and at the level of the hollow fibre. During the flow process at the level of the header it is necessary to conserve a laminar flow characteristic with a low wall shear rate combined with a exposition time of the blood.
  • the placement of the two blood inflow connectors 201 and 202 should be placed at the opposite side given by an angle of 180 °.
  • the positions of both connections relative to the z-axis which is the axis of the cylinder in the vertical view are different.
  • the connector 202 is between 0,1 cm to 1.0 cm displaced in the axis of the flow to connector 101.
  • the blood flow characteristics and blood shear forces as illustrated in Figure 3a and 3b are in this sense optimized.
  • Figures 3a illustrates the physical factor affecting blood trauma at the level of the hollow fibres represented by the wall shear ⁇ and the exposition time t.
  • the effective length of the fibres was 17 cm;
  • Figures 3b illustrates the physical factor affecting blood trauma at the level of the header cap represented by the wall shear ⁇ and the exposition time t.
  • the wall shear rate has been calculated according to the Navier-Stokes differential equation, for the case of exact solutions in a for a 3-dimensional rotation symmetric flow conditions in a convergent and wall.
  • the critical shear stress level of red blood cells and platelets are known to be related to the exposure time and to the wall shear stress at any level of the system.
  • the blood trauma as the amount of hemoglobin released from blood red cells induced through a physical factor: ⁇ *t 1/2 (10) ⁇ is the shear rate and t is the exposition time of the red blood cell in the fibres.
  • ⁇ *t 1/2 10
  • N the physical factor ⁇ *t 1/2 influencing blood cell trauma.
  • the bundle of hollow fibres 205 which is preferably provided with spacer is placed in the housing tube for which diameter may vary between 5 and 12 cm. Potting material such as the thermoplastic polyurethane is injected in a fluid form trough both dialysate connectors 207 and 211 into the end of each fibre bundle. After centrifugation and solidification of the potting at the end of the fibre bundle, the potting- fibre end is cut to a smooth surface. Thereafter, the 0-rings 213 are placed prior the fixing of both header caps, which preferably screwed and glued according to the CE-market guidelines.
  • the operation of treatment is described as follows:
  • the blood first is guided from patient with the help of the blood pump 101 at a flow rate of Q B via a blood line and enter through the connection 201 of the device.
  • the patient incoming blood is mixed with cycled and cleaned blood in 3 the internal space of the first header at a ratio of one volume to N volume.
  • the blood passes through the dialyser at a flow rate of (N+1)*Q B in a counter- current to dialysate flow in which toxins are removed from the blood by convection and diffusion.
  • one volume part minus ultrafiltrate volume is pumped through to the patient via port 209 at a flow rate Q B minus ultrafiltration rate Q UF and N volume is recycled via port 208 at of flow rate of N*Q B .
  • Example of dialysers with different surface area have been tested especially for their performances in respect to clearances of urea (illustrated in Figure 4) representative for small molecules and of vitamin B12 (illustrated in Figure 5) representative for middle molecule.
  • the example of dialysers have also been tested for phosphate clearance when varying N. As it can be seen from Figure 6, increasing N is also related to a significant increase of phosphate clearances, when comparing with standard dialysis.
  • Another particularity of the present invention is also the improved removal of the protein bound toxins as shown in Figure 7 and which is not improved by standard dialysis even when using high flux dialysers. When using high performance membranes, the improvements are significantly higher as illustrated.
  • the clinical importance of albumin bound toxins has been established, since the toxins are related to the uraemia syndrome, which has to be improved in future developments.
  • the present embodiment also can be applied for acute liver system while removing such classes of toxins in a simple way.
  • Another aspect is the improvement in eliminating a middle molecules such as the insulin marker and ⁇ 2-microglobuline as shown in Figure 8 and 9.
  • Figure 4 shows Urea in vitro clearances as a function of n cycles and membrane surface areas for a blood flow of 200 ml/min, the dialysate flow was 800 ml/min and a ultrafiltration rate of 10 ml/min.
  • the cycling number N was between 0 and 5, the membrane surface area of the dialyser prototypes were between 0.5 m 2 and 1.5 m 2 .
  • the testing has been performed in vitro using a solution as medium.
  • the membrane used was low performance polyethersulphone (Membrana).
  • the dialyser and apparatus embodiment were as described in example 1 ;
  • the test in vitro experiments were performed as follows: an open loop-dialysis circuit was mounted in a prototype of a dialysis machine as described in figure 1.
  • Figure 5 shows Vitamin B12 in vitro clearances as a function of n cycles and membrane surface areas.
  • the membrane used was low performance polyethersulphone (Mem- brana).
  • the dialyser and apparatus embodiment were as described in example 1. The experiences were assessed according to figure 4, except that the concentration of vitamin B12 was 35 ⁇ mol/l, whereas vitamin B12 measurements were performed photo metrically at 550 nm.
  • Figure 6 shows Phosphate in vitro clearances as a function of n cycles and membrane surface areas.
  • the membrane used was low performance polyethersulphone (Mem- brana).
  • the dialyser and apparatus embodiment were as described in example 1.
  • the experiences were assessed according to Figure 4, except that the concentration of phosphate was 50 mg/l.
  • the phosphate clearance has been performed using the molybdate method (Dr Lange LCK 349, Berlin Germany).
  • Figure 7 shows Indoxyl sulphate clearances as a function of n cycles and membrane surface areas.
  • the membrane used was high performance polyethersulphone (Membrana).
  • the dialyser and apparatus embodiment were as described in example 1 , except that the medium was pooled ureamic plasma.
  • the indoxyl sulphate clearance has been performed by the HPLC by reverse phase chromatography after protein precipitation.
  • Figure 8 shows Insulin clearances as a function of n cycles and membrane surface areas.
  • the membrane used was high performance polyethersulphone (Membrana).
  • the dialyser and apparatus embodiment were as described in example 1 , except that insulin concentration was 2% w/v. Insulin was assessed enzymatically using the hexokinase/phosphoglucose-isomerase method (Behringer, Mannheim, Germany)
  • Figure 9 shows ⁇ 2-microglobulin clearances as a function of n cycles and membrane surface areas.
  • the membrane used was high performance polyethersulphone (Membrana) .
  • the dialyser and apparatus embodiment were as described in example 1 , except that the medium was pooled uraemia plasma.
  • ⁇ 2.microglobuline was measured via a sandwich ELISA.
  • the essay employed 96-well Maxsorb plate (Nunk, Denmark) coated with a rabbit polyclonal anti-human ⁇ 2-microglobulin antibody (DAKO, Hamburg, Germany).
  • ⁇ 2-microglobulin in standards (DRG, Marburg, Germany) and samples was detected by incubation with a secondary rabbit polyclonal anti-human ⁇ 2-microglobulin antibody (DAKO) coupled to horseradish peroxidase, followed by colour development.
  • DAKO secondary rabbit polyclonal anti-human ⁇ 2-microglobulin antibody
  • Figure 10 shows ⁇ 2-microglobulin elimination during 4 hours as a function of n cycles and membrane surface areas in a hemodiafiltration with a post dilution of 12 litres substitution.
  • the membrane used was high performance polyethersulphone (Membrana).
  • the dialyser and detection method were as described in example 1 , except that the apparatus embodiment was as described in example 2.

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Abstract

La présente invention concerne un appareil de dialyse utile pour l'hémodialyse ou l'hémodiafiltration, qui comprend un chemin d'écoulement du dialysat, un chemin d'écoulement du sang extracorporel et un dispositif de dialyseur (104), ledit appareil comprenant un/des moyens permettant d'effecteur des cycles de reperfusion dans lesquels le sang est recyclé plus d'une fois dans ledit dispositif de dialyseur (104).
PCT/EP2005/053580 2005-07-22 2005-07-22 Hemodialyse ou hemodiafiltration differentielle WO2007009496A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200164122A1 (en) * 2017-06-08 2020-05-28 Case Western Reserve University Devices and methods for nitrosylation of blood

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5588959A (en) * 1994-08-09 1996-12-31 University Of Washington Hemodialysis recirculation measuring method
WO2000064510A1 (fr) * 1999-04-23 2000-11-02 Nephros Therapeutics, Inc. Circuit extra-corporel et methodes correspondantes
EP1170023A2 (fr) * 2000-07-04 2002-01-09 BELLCO S.p.A. Machine de dialyse
US6641731B1 (en) * 1998-12-15 2003-11-04 Fresenius Medical Care Deutschland Filter device
US20040017201A1 (en) * 1992-09-30 2004-01-29 Brugger James M. Differential fluid parameter determination
EP1466657A1 (fr) * 2003-04-11 2004-10-13 Gambro Lundia AB Dispositif de filtration avec plus d'une chambre à filtration

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040017201A1 (en) * 1992-09-30 2004-01-29 Brugger James M. Differential fluid parameter determination
US5588959A (en) * 1994-08-09 1996-12-31 University Of Washington Hemodialysis recirculation measuring method
US6641731B1 (en) * 1998-12-15 2003-11-04 Fresenius Medical Care Deutschland Filter device
WO2000064510A1 (fr) * 1999-04-23 2000-11-02 Nephros Therapeutics, Inc. Circuit extra-corporel et methodes correspondantes
EP1170023A2 (fr) * 2000-07-04 2002-01-09 BELLCO S.p.A. Machine de dialyse
EP1466657A1 (fr) * 2003-04-11 2004-10-13 Gambro Lundia AB Dispositif de filtration avec plus d'une chambre à filtration

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200164122A1 (en) * 2017-06-08 2020-05-28 Case Western Reserve University Devices and methods for nitrosylation of blood

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