Home Hemodialysis systems

FIELD OF INVENTION

This invention is in the field of medical instruments for processing body fluids including an instrument to perform hemodialysis treatment or peritoneal dialysis.

STATE OF THE ART

Currently, the most widely used method of kidney dialysis for treatment of end stage renal disease is hemodialysis. In hemodialysis, the patient's blood is cleansed by passing it through a filtration means (for instance a dialyzer) and the treatment may be controlled by a dialysis machine. During dialysis, venous and arterial parts of blood line convey a patient's blood to and from the filtration means. Impurities and toxins are removed from the patient's blood by diffusion or convection across a membrane in the filtration means. Hemodialysis is generally required three times a week with each dialysis requiring four to five hours in a dialysis center or at home. During the treatment, the patient is connected to a hemodialysis machine and the patient's blood is pumped through the machine. Catheters are inserted into the patient's veins and arteries so that blood can flow to and from the hemodialysis machine. A large amount of a dialysis solution, for example about 120 liters, is consumed to dialyze the blood during a single hemodialysis therapy.

Peritoneal dialysis, although used less frequently than hemodialysis, is an accepted method for treating end stage renal disease. It is becoming increasingly a more popular form of dialysis. In peritoneal dialysis, a dialysis solution is infused into a patient's peritoneal cavity using tubing and a catheter. The peritoneum, which defines the peritoneal cavity, is composed of a membrane that contains many small blood vessels and capillary beds, in such a way that the peritoneal membrane acts as a filtration means. Peritoneal dialysis uses a dialysis solution or "dialysate", which is infused into a patient's peritoneal cavity via a catheter. The dialysate contacts the peritoneal membrane of the peritoneal cavity. Waste, toxins and excess water pass from the patient's bloodstream, through the peritoneal membrane and into the dialysis solution due to diffusion and osmosis, i.e., an osmotic gradient occurs across the membrane. The spent dialysate is drained from the patient, removing waste, toxins and excess water from the patient. This cycle is repeated and uses also a large amount of a dialysis solution.

The peritoneal cavity may be compared to the filtration means used in hemodialysis. Indeed, in both cases, impurities and toxins in the blood are removed across a filtration means. Hemodialysis and peritoneal dialysis are two types of dialysis therapies used commonly to treat loss of kidney function. Although dialysis equipment for home use is available, a patient must still remain relatively immobile during the course of treatment due to the non-portable nature of such dialysis equipment. Typical home-dialysis equipment employs an amount of dialysis fluid greater than 20 liters and typically up to 120 to 200 liters. Thus the patient has to store at home a large volume of fresh dialysate and the patient hands several dialysate bags (fresh and spent) every day for treatment. Other machines allow transforming water into dialysis solution but these machines use a large amount of energy and water, while representing a potential contamination risk. In both cases, the environmental impact is important. Another drawback of these dialysis systems using the water is the need for a dedicated water treatment, which includes equipment, water connection and drainage. Installing and using those components is a difficult and cumbersome task that can require a patient's home to be modified.

The large volume of dialysate required for dialysis is in part attributable to the large quantity of solution necessary for the diffusion of waste products removed and the balancing of electrolytes within the dialysate from the blood of a dialysis patient. Regeneration of spent dialysate is one way to reduce the total volume of a dialysis system by eliminating the need for a large reserve of fresh dialysate. In order for spent dialysate to be reused, accumulated waste products and impurities must be removed from the spent dialysate, and the composition and pH of the regenerated dialysate must be regulated for physiological compatibility. Devices that regenerate spent dialysis fluid are primarily directed toward the removal of urea, ammonium ions, uric acid, creatinine, and phosphate via various sorbents. For example, the Recirculating Dialysate System ("REDY system"), which was introduced in the 1970s, employs a sorbent cartridge through which spent dialysate is recirculated and regenerated. However, the regenerated dialysate produced by REDY systems is subject to variations in pH and sodium concentrations and therefore become non-conducive to physiological norms.

The most recent machines can regenerated a dialysis solution and injects - via a dedicated pump and/or dedicated device - sodium or other components into the dialysis solution which has flowed through the sorbent. One of drawbacks of these machines is the use of a specific device or pump, so that the machines are complex, expensive and comprise several elements which use energy. Furthermore, this type of machine is large, expensive and heavy, making it inappropriate to use at home and for patient transportation.

GENERAL DESCRIPTION OF THE INVENTION

All mentioned drawbacks may be obviated by the device for dialysis system according to the invention.

In one aspect of the invention, a dialysis system has a size and weight suitable to be used at home while enabling transportation. In one aspect of the invention, a dialysis system comprises a regeneration system which is at least in part incorporated into a dialysate circuit in such a way as to simplify the dialysis system, while limiting the elements needed to regenerate a dialysis solution at lower cost. In one aspect of the invention, a dialysis system comprises a cassette comprising channels which may be used by a dialysis solution and a regeneration solution in such a way as to simplify the fluid pathway. In one aspect of the invention, a dialysis system incorporates a filtration means and a sorbent device configured to allow dialysis solution to pass through. The filtration means is adapted to remove one or more substances from the blood of a patient. The filtration means can be a peritoneal cavity of a patient or at least one dialyzer. The sorbent device is adapted to remove one or more substances from a dialysis solution. The device can be made out of one or more sorbent cartridges. Preferentially, the dialysis system is configured to blend a regenerated solution into a dialysis solution. In one embodiment, the dialysis system comprises at least one by pass in such a way as to bypass the sorbent device and/or the filtration means. The by-pass is particularly useful when a dialysis solution does not need to flow through the sorbent device or when the regeneration solution is conveyed to a bag, via part of the dialysate pathway which may bypass the sorbent device, for instance a mixing bag.

In one embodiment which may not comprise a sorbent device, a by-pass may be used as a security means, for instance to convey a used dialysis solution - which is not good to use - through another pathway rather through a filtration means. It may also be useful, for example, if the dialysis solution is too hot or too cold, or non-conducive according to physiological norms. Thus, the dialysis solution may pass one more time through the dialysis machine or convey to a bag (waste bag or mixing bag) without flowing through the dialyzer. In one aspect of the invention, a hemodialysis system comprises only one pumping means (for instance only one pump, e.g. peristaltic pump,...) for moving the dialysis solution through the dialyzer. Thus, said pumping means is adapted to convey (push) the dialysis solution to the dialyzer and/or to remove (pull) the dialysis solution from the dialyzer. For instance, the pump may be adapted to move a dialysis solution from a bag to a dialyzer and/or from the dialyzer to the bag and trough a sorbent device. In one embodiment, the hemodialysis system comprises a valve so as to close a channel, for instance the channel which conveys the dialysis solution to the dialyzer. Thus when this valve is open the hemodialysis system performs diffusive clearance and convective clearance by pressurizing the fluid through the dialyzer and when this valve is closed the hemodialysis system performs only a convective clearance by sucking fluid from the dialyzer.

In one embodiment, the hemodialysis system comprises a controller adapted to control the flow, the flow rate and/or the pressure inside the channels which extends to the dialyzer and/or from the dialyzer in such a way to perform a determined percent of diffusive clearance and/or a determined percent of convective clearance. For example, the hemodialysis system may comprise at least one proportional valve located in the channel which conveys the dialysis solution to the dialyzer and/or in the channel which conveys the dialysis solution from the dialyzer. Said at least one proportional valve is commanded by a controller comprised in the hemodialysis system.

In one aspect of the invention, a method for regenerating a dialysis solution uses the same pumping means for conveying all or part of a dialysis solution as well as a regeneration solution.

LIST OF FIGURES

The present invention will be better understood at the light of the following detailed description which contains non-limiting examples illustrated by the following figures:

Figures 1 , 2 and 3 show a schematic view of three distinct possible embodiments Figure 4 illustrates the filtration means

Figure 5 and 6 shows a schematic view of two distinct possible dialysate circuits Figure 7 shows a schematic view of a blood circuit

Figures 8, 9 and 10 show a schematic view of three distinct possible embodiments Figures 11 shows a schematic view of another embodiment which can perform backfiltration mode

LIST OF ELEMENTS

1 Fluid distribution system

2 Filtration means

2' Embodiment wherein the filtration means is a peritoneal cavity

2" Embodiment wherein the filtration means is a dialyzer or multi-dialyzers

3 Bag

4 Bag

5 Bag

6 Bag

7 Heater

8 Sorption unit

9 Valve

10 Pressure sensor

1 1 Temperature sensor

12 Scale

13 Channel

14, 14' Cassette

15 Pumping means

16 First channel

17 Second channel

18 Third channel

19 Dialysate circuit

20 Other fluid circuit (Blood,...)

21 Pump

22 First bag

23 Sorbent device

24 Second bag 25 Filtration means

26 First line

27 Second line or first by-pass

28 Third line or second by-pass

30 Fluidic pathway in which a fluid flows from a filtration means to a pump

31 Fluidic pathway in which a fluid flows from a pump to a sorbent device

32 Fluidic pathway in which a fluid flows from a sorbent device to a reservoir

33 Fluidic pathway in which a fluid flows from a reservoir to a filtration means

40 Fluidic pathway in which a fluid flows from a pump to a filtration means

41 Fluidic pathway in which a fluid flows from a filtration means to a sorbent device

42 Fluidic pathway in which a fluid flows from a sorbent device to a reservoir

43 Fluidic pathway in which a fluid flows from a reservoir to a pump

50 Dializer

51 Sorbent device

52 Optional heater

53 Scale

54 Mixing bag

55 Additive bag

56 Dialysate flow

57 Blood line

58 Blood line

59 Cassette

V. Valve

S. Sensor

P. Pressure sensor

T. Temperature sensor

DETAILED DESCRIPTION OF THE INVENTION

The invention is set forth and characterized in the independent claims, while the dependent claims describe other characteristics of the invention. In the following detailed description, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration several embodiments of devices, systems and methods. It is to be understood that other embodiments are contemplated and may be made without departing from the scope or spirit of the present disclosure. The following detailed description, therefore, is not to be taken in a limiting sense.

The present application claims the benefit of the priority of PCT/IB2014/061006 filed on 25 April 2014 in the name of Debiotech S.A., the entire disclosure of which is incorporated herein by reference.

All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. The definitions provided herein are to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.

As used in this specification and the appended claims, the singular forms "a", "an", and "the" encompass embodiments having plural referents, unless the content clearly dictates otherwise.

As used in this specification and the appended claims, any direction referred to herein, such as "top", "bottom", "left", "right", "upper", "lower", and other directions or orientations are described herein for clarity in reference to the figures and are not intended to be limiting of an actual device or system. Devices and systems described herein may be used in a number of directions and orientations.

As used herein, "have", "having", "include", "including", "comprise", "comprising" or the like are used in their open ended sense, and generally mean "including, but not limited to. As used in this specification and the appended claims, the term "or" is generally employed in its sense including "and/or" unless the content clearly dictates otherwise.

As used herein, the term "cassette" refers to an element of a fluid distribution system. A cassette comprises a number of defined channels, valves and fluidic connection means. The fluidic connection means (also named connection port) are designed to make possible a fluidic connection between a channel of the cassette to an element which is located inside or outside the cassette. For instance, a pumping means may be connected to at least one channel of the cassette, the inlet and outlet of the pumping means may cooperate with the cassette in such a way as to be the fluidic connection means. Said pumping means may be outside the cassette or at least in part arranged into the cassette. The fluidic connection means may extend externally from the cassette to an element via a tube or directly so that the fluidic connection means may rigidly fix the element to the cassette. The fluidic connection means may comprise a dedicated valve.

The cassette may be a disposable element which cannot be reused after a single treatment. The cassette may be secured to a cassette holder of a dialysis machine of the dialysis system. The dialysis machine can be reused several times and reused with distinct cassettes. The fluid distribution system may include pumping means for moving the fluid through the dialysis system, sensor for monitoring the treatment and actuators for opening and closing valves. Thanks to the valve and the pumping means, the dialysis machine controls the fluid distribution system. The dialysis machine may be commanded by an electronic processor so that the treatment can be performed, at least in part, automatically.

As used herein, the term "channel" of a cassette refers to a fluid passageway which is arranged into the cassette and defined by the fluidic connection means. In case when two distinct channels are connected there between by a valve, the limit of said channels is said valve so that said valve may be understood as a fluidic connection means. As used herein, the term "line" refers to a fluid passageway in which a fluid flows. A line may comprise elements which can change the physical and/or chemical characteristics of the solution. For example, a dialysate circuit comprises at least one line in which a dialysate solution flows, such line may comprise a sorbent device or filtration means.

As used herein, the term "fluidic pathway" refers to a fluid passageway which allows conveying a fluid from an element to another element, said element acting on the fluid (pumping, filtering, storing...). For example: a solution line comprises a pump, a dialyzer and a sorbent, all elements being connected there between. In one embodiment, three distinct fluidic pathways can be distinctively defined:

- a first fluidic pathway between the pump and the dialyzer,

- a second fluidic pathway between the pump and the sorbent device (or sorption unit) and

- a third fluidic pathway between the sorbent device and the dialyzer.

One of said fluidic pathway may comprise a reservoir or a heater which may be used as a mixing bag or a buffer bag. A fluidic pathway may comprise valves or connection means but said valves and connection means do not define nor limit the fluidic pathway.

In other terms, a fluid distribution system comprises a line in which a solution flows. Different elements (bag, pump, filtration means, heater ...) are in fluid communication through said line with, in-between each element, defines fluidic pathways. If the fluid distribution system comprises a cassette, then a fluidic pathway may pass through a channel of the cassette. Thus, a channel may be a part of a fluidic pathway, and a fluidic pathway and a channel are a part of the line.

THE FLUID DISTRIBUTION SYSTEM In a haemodialysis treatment system, the fluid distribution system comprises at least two distinct circuits which are the blood circuit and the dialysate circuit. The blood circuit comprises a single line in which the blood flows, a filtration means (a dialyzer) which divides in two part the line: venous part of line and arterial part of line. The blood circuit further comprises a pump which removes the blood of the patient by the arterial part of line, convey the blood trough filtration means (to remove impurity, water,...) and re-injects the blood to the patient by the venous part of line. The blood circuit may comprise a physiologic priming solution (saline) with an infusion set and/or an anticoagulant, such as heparin or sodium citrate and calcium. Typically, at least a part blood circuit is disposable, in particular, the elements, which have been in contact with the blood, have to be discarded after use. The figure 7 shows a schematic view of the blood circuit. During the treatment, a pump of the blood circuit is pumping continuously. An interruption of the blood flow increase the risk of blood clotting, therefore a continuous flow is recommended. The blood circuit may comprise two valves, (access and return) which remain opened during the treatment. For example, these valves can close in order to protect the patient in case of a risk (e.g. blood leak from the set or to avoid air injection). The blood circuit may comprise three sensors for monitoring the pressure: at the patient access, at the patient return and at the outlet of the pump before the filter if the blood is pumped through the filter at positive pressure (or at the inlet of the pump in case the blood is sucked from the filter at negative pressure). These sensors can detect abnormal pressures that can result from an occlusion or a bad connection. An air trap may be placed after the filter for collecting the air before the blood returns to the patient. If some air however escapes from the air trap, an air sensor detects it and the flow can be stopped before this air reaches the patient. The blood circuit may comprise an infusion set of anticoagulant (e.g. heparin) which may be placed as close as possible of the patient access. Alternatively, sodium citrate can also be injected as close as possible to the patient access, in order to prevent coagulation, in which event calcium will need to be injected in the blood flowing back to the patient after the filter to neutralize the citrate anti-coagulation effect. The figures 1 , 2 and 3 show schematic views of different embodiments of the dialysate circuit. The dialysate circuit comprises at least one valve (9), at least one line (16, 17, 18) and a pump (15). The fluid distribution system include at least one bag (3, 4, 5, 6) which may comprise:

- a dialysis solution:

o fresh (i.e. new dialysate ready for the treatment), or

o spent (i.e. a dialysate which is already used, for instance after having passed through the filtration means), or

o regenerated (i.e. a spent dialysate which has flowed through a sorption unit blended, or not, with a regeneration solution), or - a regeneration solution, or

- other solution (e.g. heparin, ...).

Said dialysate circuit is connected to a filtration means. As showed in figure 4, said filtration means may be a peritoneal cavity of a patient (if the treatment is a peritoneal dialysis) or a dialyzer (single or multi dialyzer) for performing a hemodialysis treatment (for instance). Multiple dialyzers may be used for different purposes (e.g. one dialyzer for blood purification, one for toxin adsorbtion, one for oxygenation, etc .). The dialysate circuit further comprises a sorbent device and the dialysate circuit is adapted to:

- pass a dialysate solution through the filtration means (so that remove from the blood of patient impurity, water, waste...),

- remove the spent dialysate solution from the filtration means,

- pass the spent dialysate solution through the sorbent device (to remove from the spent dialysate solution the impurities, waste...).

Thanks to this circuit, a dialysate solution can be reused several times at least during one multiple hours treatment. Nevertheless, the drawback of a sorbent device is that it removes too much components of the dialysate solution (for instance calcium, magnesium,...) which makes the dialysate solution non ideal for use through further cycles. Therefore, a regeneration solution has to be injected into the dialysate circuit to regenerate a dialysate solution which can be used again for the treatment. The use of a conductivity sensor helps ensuring the proper electrical conductivity of the regenerated solution, such conductivity being representative of the mixing.

The figure 5 shows a schematic view of a fluid distribution system comprising a dialysate circuit in which the pump (21 ) conveys a dialysate solution through the first line (26). The dialysate solution passes through the filtration means (25) then through the sorbent device (23). The fluid distribution system comprises at least one bag (22, 24) for storing a dialysate solution, a regeneration solution or a priming solution. Preferentially, the fluid distribution system comprises a first bag in which is stored a regeneration solution and the fluid distribution system (1 ) is adapted to use the same pump (21 ) for conveying the regeneration solution from the first bag (22) to the dialysate circuit.

In one embodiment, the pump (21 ) is located between the filtration means (25) and the sorbent device (23) in such a way that a dialysate solution flows from filtration means (25), passes by the pump and then reaches the sorbent device (23).

In one embodiment, the regeneration bag (22) may be optional or replaced by a fresh dialysate solution bag.

In a preferred embodiment, the dialysate circuit comprises a second line (27) (so named first by-pass) adapted to bypass the sorbent device. Thus, a solution can:

- flow through the sorbent device (23) or

- reach the first line (26) after the sorbent device so that the solution does not pass through the sorbent device (23) so that it content is not modified. If the dialysate device comprises a second bag (24), the solution, which flows through the first by-pass (27) can directly reach the second bag (i.e. without passing through the sorbent device).

In one embodiment, the second bag (24) is a mixing bag in which a dialysate solution may be blended with a solution (for instance a regeneration solution). Nevertheless, the dialysate circuit can also be used without this second bag. In this case, the first by-pass (27) may be connected to the first line (26) (after the sorbent device (23) or directly to the filtration means (25).

In a preferred embodiment, the dialysate circuit comprises a third line (28) (so named second by-pass) adapted to bypass the filtration means. Thus, a solution can:

- flow through the filtration means (25) or

- reach first line (26) after the filtration means so that the solution does not pass through the filtration means (25).

It's particularly useful for different reasons, for instance, if the solution is too hoot or not good to used, this solution may be deviated from the filtration means. Furthermore, if a regeneration solution is not homogeneously blended with a dialysis solution, the second by-pass may be used to improve the mixing. In one embodiment, part of the dialysate circuit is arranged into a cassette, in particular a part of the first, second and/or third line.

The pump may be a unidirectional pump which may be a peristaltic pump. In a preferred embodiment, the pump (21 ) is adapted to pump solely or in combination the dialysate solution and the regeneration solution. Thus, the fluid distribution system comprises at least one valve to select the solution to be moved. Said at least one valve may be a proportional valve so that the system can pump at same time both solutions and the proportional valve commands the ratio dialysate / regeneration. The fluid distribution system shown in figure 6 may be adapted to use a proportional valve (or any other device having the same effect). Indeed, the spent dialysate solution which comes back from the filtration means can be pulled by the pump in such a way as to reach the sorbent device (23) then to reach the pump which may pump at same time a regeneration solution (in a proportional way) so that the mixed solution (regenerated dialysate solution) can be pushed by the pump (21 ) and reach the filtration means (25) via the first line. The second bag may be placed between the pump and the filtration means. In other embodiment, the system shown at the figure 6 may comprise a second bag (24) (not shown in the fig. 6) between the sorbent device (23) and the pump (21 ), preferably connected to the end of the second line (27). The first bag (22) may be optional.

In one embodiment, the fluid distribution system may be used to perform two distinct operating modes. A first operating mode in which the pump (21 ) pulls a dialysate solution from the filtration means (25) (for instance a dialyzer) and then pushes said dialysate solution to the sorbent device (23) in order to produce a negative pressure in the dialysate side of the filtration means (compare to the blood side of the filtration means). A second operating mode in which the pump (21 ) pulls a dialysate solution from a bag (24) and then pushes said dialysate solution to the filtration means (25) (for instance a dialyzer) in order to produce a positive pressure in the dialysate side of the filtration means (compare to the blood side of the filtration means). An optional third operating mode may be used to regenerate a dialysate solution as disclose in this document.

CONTROLLER

In a preferred embodiment, the dialysate circuit may flow through a machine which comprises pumping means (1 5) and a fluid distribution system (1 ) having valves (9), in such a way as to convey a dialysis solution from point "A" to point "B". A machine comprising an electronic processor may control automatically all or particular valves and pumping means to perform automatically the treatment without help from a patient. It's particularly useful when the treatment is performed at home.

In one embodiment, the controller may control the first and second by-pass as disclosed above. Said controller may be automatic and is adapted to command the by-pass depending on the solution which is moved by the pump (21 ). If the pumped solution is a dialysis solution which has passed by the filtration means, the controller may command to convey this solution through the sorbent device (23) before to reach the second bag (24) or filtration means (25). If the pumped solution is a regeneration solution, the controller may command that this solution bypasses the sorbent device (23). If the dialysis solution cannot be used for the treatment, the controller may command to bypass the filtration means (25).

EMBODIMENTS SHOWN IN FIGURES 1 , 2 AND 3 A dialysis solution flows from a bag to the filtration means and/or vice versa. In figure 1 , the bag 3, 5 or 6 may store a fresh dialysate before starting the treatment or a saline solution. After a priming phase, the treatment can start. As a first step, a dialysis solution is taken in a bag, the pumping means (15) moves the dialysis solution to a filtration means (2). Then, the dialysis solution is removed from the filtration means (2), this dialysis solution is spent and can be named spent dialysis solution. The spent dialysis solution flows into the dialysate circuit to a sorption unit (8). Thanks to the sorption unit (8), the spent dialysis solution is converted into a semi-regenerated dialysis solution and it may be stored in the bag (3). The semi-regenerated dialysis solution may be used immediately so the dialysis solution of the bag 3 is conveyed a second time to the filtration means (2). Some time, the semi-regenerated dialysis solution needs to be blended with a volume fraction of a regeneration solution. Said regeneration solution may be calcium, magnesium and/or potassium (or other components). Thus, a volume fraction of the regeneration solution is pumped (via the pump used to move the dialysate) from the bag (4) as necessary to replenish ions that are removed via the sorption unit. This volume fraction is infused in the dialysate circuit; preferably the volume fraction is blended with the regenerated dialysate into the bag (3).

The figures 1 , 2 and 3, show three distinct embodiments but having the same first fluidic pathway (16) and the same third fluidic pathway. Indeed, the filtration means (2), the bag 4 and the pumping means (15) are fluidly connected via a fluidic pathway (16), optionally the bag (5) may be also fluidly connected to the same fluidic pathway (16). The bag 4 and 5 may store a dialysis solution or a regeneration solution or other fluid. One or more valves may be located in the fluidic pathway in such a way as to open or close the fluid communication between the elements (filtration, means, bag (s), pump...). The third fluidic pathway (18) fluidly connects the bag 3 to the filtration means (2). Preferably, the outlet of the bag (3) is fluidly connected to the inlet of the filtration means (2). A valve (9) may be located between the filtration mans (2) and the bag 3.

Optionally, the third fluidic pathway (18) and the first fluidic pathway (16) are connected via a valve (9) (i.e. a single valve or an additional fluidic pathway comprising a valve) named recirculation valve. It's particularly useful for different reasons, for instance if the solution (which flows in the third channel) is too hoot or not good to be used, this solution may be deviated into the first fluidic pathway. Furthermore, if a regenerated solution is not homogeneously blended with a dialysis solution, the recirculation valve may be used to improve the mixing (e.g. if the conductivity measured is not appropriate). Furthermore, if too much regeneration solution has been injected into the bag 3, a volume fraction of the regenerated solution (of bag 3) can flow through the sorbent device in order to improve the mixing. Referring now to figure 1 , the second fluidic pathway fluidly connects the pumping means and the sorption unit (e.g. sorbent cartridge). The bag (3) is connected to the pump (15) directly (i.e. via a fluidic pathway, in particular the second fluidic pathway) or via the sorption unit. Thus, the pumped fluid can flow through the sorption unit (8) until the bag (3) or reach directly the bag without passing through the sorption unit (8). The controller may command the valve (9) in such a way to convey the fluid directly to the bag (3) or via the sorption unit (8).

The second fluidic pathway may also extend to an additional bag (6) in which a solution (for example the Ultra filtrate) may be stored during the treatment. The system may comprise a scale (not shown) in order to measure, compute and/or estimate the volume of removed ultrafiltration which is store in the bag 6 and/or 3.

Referring now to figure 2, the additional bag (6) is withdrawn; the second fluidic pathway is connected from the pump (15) to the sorption unit (8), optionally to the bag (3) and/or optionally to the third fluidic pathway (18). Thus, the fluid can:

- flow through the sorption unit (8) to remove some impurity and then reach the bag (3). The bag (3) being connected to the filtration means via the third fluidic pathway, the fluid, which is stored in the bag (3) can reach the filtration means (2).

- reach directly the bag (3) without passing by the sorption unit (18) as disclosed above in the figure 1 . Thus the sorption unit is bypassed. For example, if the bag (5) stores a fresh dialysate, the fresh dialysate can flow from the bag (5) to the bag (3). Indeed, the sorption unit (8) can alter, in whole or in part, the dialysate so it would be preferable to bypass the sorption unit (8).

- reach directly the third fluidic pathway (18) without passing through the sorption unit (18) nor by the bag (3). For example for priming or cleaning...

Referring now to figure 3, the fluid distribution system comprises a heater (7) to heat the fluid. The second fluidic pathway (17) conveys the fluid from the pump to the sorption unit (8), optionally directly to the heater (7) or optionally directly to the bag (3). An additional fluidic pathway may connect an outlet of the sorption unit (8) to an inlet of the heater (7) or to the second fluidic pathway between an inlet of the heater and a valve (the valve of the second fluidic pathway which connects the second fluidic pathway to the heater (7)). Another additional fluidic pathway may connect an outlet of the heater (7) to an inlet of the bag (3) or to the second fluidic pathway between an inlet of the bag (3) and a valve (the valve of the second fluidic pathway which connects the second fluidic pathway to the bag (3)).

The heater can be located upstream of the sorption unit or downstream of the bag (3) or can be arranged in a cassette (if the fluid distribution system comprises a cassette) or in the bag (3).

The embodiment of the figures 1 , 2 and 3 may convey a dialysate solution from the filtration means to a bag or from a bag to the filtration means. In other terms, the pumping means may generate a negative pressure or a positive pressure in the filtration means (compared to the blood pressure in the filtration means (blood and dialysate solution being separated by a membrane in the filtration means)). PHASES OF USE

During treatment a succession of phases may be performed:

- Diffusion phase

- Ultrafiltration phase

- Dialysate recombination phase

These are described below.

Although we distinguish the different phases of essentialy Diffusion and Ultrafiltration, it is to be noted that Diffusion may also comprise some part of hemofiltration and/or ultrafiltration and Ultrafiltration phase may also comprise some part of Diffusion.

The figures 8, 9 and 1 0 are different embodiments a part of a dialysis system of which the dialysate circuit which comprises a cassette (14) or a larger cassette (14').

Each embodiment comprises a cassette (14, 14') having valves (9) and at least one connection port intended to be connected to a filtration means (2), a first supply bag (4) for storing a regeneration solution, a single pumping means (1 5) which may convey a dialysis solution, a sorption unit (8) and a second bag (3).

The cassette (14, 14') may comprise:

A first channel having two connection ports (which may externally extending from the cassette), of which one connection port intended to be connected to the first supply bag, and one connection port intended to be connected to the filtration means,

A second channel having a connection port (which may externally extending from the cassette) intended to be connected to the sorption unit (8), and

A third channel having two connection ports (which may externally extending from the cassette), of which one connection port intended to be connected to the second bag (3) and one connection port intended to be connected to the filtration means (2). Preferentially, the first channel and the second channel are connected to said single pumping means (15) and the single pumping means (15) is operable to convey the dialysis solution from the filtration means to the sorption unit and the regeneration solution from the first bag (4) to the second bag (3). The pumping means (15) may be arranged into the cassette (14, 14'). The system may comprise a heater to heat a dialysate solution. Said heater may be arranged inside the cassette. If the heater is outside of the cassette, the cassette may comprises at least one connection port which externally extends from the cassette, said connection port may be intended to be connected to an inlet and/or outlet of the heater. The heater may be arranged into the bag (3).

The system may comprise sensors (air sensor, pressure sensor, ammonia sensor, scale...) to monitor the treatment. At least one sensor may co-operate with the cassette. In particular the system may comprise a conductivity sensor for monitoring the dialysis solution which flows through the system.

The embodiment of the figure 9 discloses two by-pass means. The first one is the by-pass which allows bypassing the sorption unit and/or the heater. Said by-pass means is arranged in the second channel and comprises valves which allow or not the communication to the sorption unit (8), heater (7) and/or the bag (3). The second by-pass means is represented by a fluid passageway between the first channel and the third channel. Said fluid passageway is commanded by the recirculation valve, which may limit the channels.

Diffusion phase

Referring now to figures 8 and 9, during this phase the patient is actually treated based on a principle of diffusion (hemodialysis and/or hemofiltration). The dialysate circulates through the filtration means (2) pumped by the pump (15) from the mixing bag (so called second bag (3)). The dialysate may also be pulled from the filtration means (2) in such a way as to perform in part a convective clearance at the same time (hemofiltration). The used dialysate is pushed into the sorption unit (8) that will remove toxins but also some components of the dialysate (such as Calcium and Magnesium). The fluid may go then into a heater (7) to maintain the temperature of the dialysate in order to warm-up the blood when passing through the dialyser. A temperature of the dialysate near the body temperature prevents the cooling of the blood in the extra-corporal system. A solution (e.g. a regeneration solution) may be then added in the mixing bag (3) that contains already a certain amount of dialysate. To create this circuit, the valve 1 , 5 and 7 are opened (and 9 for the figure 9). Typically the regeneration solution contains Calcium, Magnesium and other components.

The pressures may be monitored with sensors (10) before and after the pump (15) and also between the mixing bag (3) and the filtration means (2). These pressure sensors are used to detect occlusion.

The fluid temperature may be measured before and after the heater (2) for regulation. Like the dialysate that flows into the filter from the mixing bag (2), the temperature of the dialysate in this mixing bag (3) is measured by two distinct temperature sensors. Both measurements ensure the required safety in case of failure of one sensor.

In one embodiment, with an adequate arrangement of the tubes or channels, the mixing bag (3) can serve as a mean to accumulate any amount of circulating air (including the air coming from the priming). If some air escapes from the bag because, for instance, not enough dialysate is present inside the bag, the air sensor placed after the bag can detect it. A rupture of the fibers inside the filter may also be considered. In this case some blood will enter in the dialysate fluidic pathway and a blood sensor may be placed after the pump to detect this failure (e.g. a colour sensor).

An ammonia sensor may be placed after the sorption unit to control the proper functioning of the sorption unit (8). In the event the sorption unit is exhausted and cannot filter dialysate anymore it will release ammonia. This sensor can therefore also be used in order to detect the end of use of the sorbent unit. A conductivity sensor may be placed after the mixing bag (3) to control the electrolyte level of the dialysate. The accuracy of the electrolytes concentration of the dialysate is however generally based on the accuracy of the pump (15) and on the accuracy of an optional scale (12) rather than on the conductivity sensor which serves only as a security means.

During this phase, the scale (12) may monitor the mixing bag (3) weight and measures the ultra-filtrate (UF) extracted. The UF is extracted by the diffusion process, but also by the pressure difference through the membrane of the filter (transmembrane pressure) by principle of convection (hemofiltration). This pressure is created by the flow resulting from the pressure differential between the dialysate side and of the blood side. Ultrafiltration is used therefore to define the amount of fluid extracted from the patient by both diffusion and convection.

Ultrafiltration phase

The UF obtained during the diffusion phases is maybe not sufficient to reach the required value. To obtain the required volume, another phase, dedicated more specifically to the UF extraction can optionally be performed. The principle used in this phase is convection by creating negative pressure with the pump on the dialysate side of the filter (e.g. by sucking with the pump from the dialysate outlet of the filter, applying a negative pressure on the dialysate side of the filter).

During this phase, the flow of dialysate through the filtration means (8) is interrupted, blocked by closing the valve 7. Only the valves 1 and 5 (and 9 for the figure 9) are opened and the pump (15) extracts the UF from the filtration means (8) by applying a negative pressure on the filter dialysate side. The extracted volume can be measured by the scale (12). The pressures may be monitored with sensors before and after the pump. The ammonia sensor may control the proper functioning of the sorbent. The temperatures may be measured by the same way than during the diffusion phase but with an adapted heating control according to the extracted volume considered. li is to be noted that, in most of the cases, a combination of both Diffusion and Convection can be obtained in each of the Diffusion and Convection modes, although the proportion of each may be different.

Dialysate recombination phase

During the filtration phase, the solution coming from the mixing bag (3) may not be regenerated in an ideal way (lack of certain electrolytes because of the sorption process). This may not represent a problem as long as the concentration is not excessively effected (the larger the amount of fluid in the mixing bag, the lesser the problem). When such concentration may not be sufficient, a regeneration cycle shall be implemented.

During this regeneration phase, the flow of dialysate through the filtration means (2) is interrupted. The valve 2 and 6 are opened, a solution (regeneration solution) that contains the required electrolytes at a high concentration level is pumped to the heater (7) and then in the mixing bag (3). According to the figure 9, the regeneration solution may bypass the heater to increase the accuracy of the injected regeneration solution, in which case the valves 2 and 8 are opened. The resulting concentration of the dialysate electrolyte is driven by the volume of depleted dialysate pumped in the mixing bag (3) (measured by the dialysate pump during the diffusion phase), by the volume of concentrate (measured by the scale during this present phase) and by the accuracy of the concentration of the electrolytes in the initial dialysate and in the concentrate. During the next phase following this recombination phase, a small amount of fluid may be pumped with the valve 6 opened and the valve 5 closed to flush the concentrate and prevent the concentrate to enter in the sorption unit.

The pressures may be monitored with sensors before and after the pump to detect occlusion. The temperatures may be measured by the same way than during the diffusion phase but with an adapted heating control according to the recombination volume considered. Alternating phases

The end of the treatment may be depending on the amount of removed ultra- filtrate. Thus, the aim of the system may be to reach a required amount of ultra- filtrate which may be determined by a caregiver over the therapy.

As disclosed above, during the diffusion phase the system removes some ultra- filtrate, but sometime this phase cannot reach the required value. Thus, the system may be adapted to switch between at least one diffusion phase and at least one ultrafiltration phase in such a way as to reach the determined amount of ultra-filtrate. One or more regeneration phase may be also performed during this treatment. This method of alternating phases is due to the design of the system which comprises only one pump for conveying a dialysate solution and the ultra- filtrate. It is also preferably to remove the ultra-filtrate progressively, to avoid patient blood pressure drop, during the entire treatment time.

Thus, the hemodialysis system is adapted to start a diffusion phase and after a determined time or depending on the amount of removed ultra-filtrate, the system stops the diffusion phase (prevents the dialysate solution to reach the dialyzer, for example, closing the valve 7) in such a way to perform an ultrafiltration phase (which may also include hemofiltration). The system may switch between this both phases on a determined frequency. The frequency may be computed or suggested by the system or determined by a caregiver. The frequency may depend on the determined amount of removed ultra-filtrate and maybe the duration of the treatment as well as the patient blood pressure which may be monitored during the treatment.

In one embodiment, to know the amount of the removed ultra-filtrate, the system comprises a scale which measures the solution amount contained in the mixing bag (3). The scale may be wirelessly connected to the system. During the diffusion phase, the mixing bag stores a dialysate solution and the removed ultra- filtrate. While during the ultrafiltration phase, the removed solution is substantially the ultra-filtrate which may be stored in the mixing bag. The system is adapted to compute the ultra-filtrate during both phases. The system measures the solution stored in the mixing bag and computes the total amount of removed ultra-filtrate. When the total amount of removed ultra-filtrate is equal to the required value at a certain time of the therapy, the system may stop the process.

OTHERS EMBODIMENTS

In certain circumstances, it may be preferable to combine convection and hemodialysis, as well as hemo-diafiltration, in order to improve the elimination of certain toxins from the blood (such combination today requires at least two pumps to be operated). In such a case, it may be necessary to compensate for the excess of ultra-filtration (or water removal) obtained through such procedure. In case the dialysate fluid cannot be directly administered to the patient, the best is to apply a back-filtration, meaning that fluid will be re-administered to the patient through the dialysis filter by applying a positive pressure on the dialysate side of the filter through the sequence described above. By combining both, a negative pressure on the dialysate side of the filter (to perform hemo-diafiltration) followed by a positive pressure on the dialysate side of the filter (to perform a back- filtration), the system according to the invention improves the performance of the dialysis while only using one pumping system and a more accurate balancing. In addition, using the dialyzer as a filtration means during the back-filtration helps preventing potential contamination on the patient side (bacteria cannot flow through the membrane of the filter which acts like a sterilization filter).

The embodiments disclosed above can be used to perform a diffusion clearance and/or a convective clearance. In cases where the UF obtained during the treatment also exceeds the required value, it would be essential to provide a determined amount of a solution (for instance water or dialysate solution) back to the patient. During the treatment, too much water may be removed from the blood of the patient. Indeed, according to the embodiment shown at figures 5, 8, 9 and 10, the pumping means is located just after an outlet of the filtration means so the pumping means pulls the dialysate solution. This arrangement of the pumping means produces a negative pressure in the dialysate side of the filtration means (for instance a dialyzer) compared to the blood side of the filtration means. In other terms, during the diffusion phase, a convection clearance may be performed. Especially as shown by the figure 7, the blood is pushed by the pump into the blood part of the filtration means and the dialysate solution is pulled from the dialysate part of the filtration means by the dialysate pump causing a pressure differential.

In one embodiment which is not show by the figures, a determined amount of a dialysate solution may also be injected into the blood line directly before or after the filtration means, named respectively pre and post dilution. In this embodiment, a second pump may be located between the blood line and the dialysate line. Said pump is operable to inject dialysate solution into the blood line before and/or after the filtration means during a specific phase or during the diffusion phase or during the ultrafiltration phase. This is usually called CRRT, although in the embodiment of the invention this can be done with only 2 pumps on the dialysate side, versus 3 pumps in conventional systems. Such a system is particularly used in Intensive Care where the treatment can be maintained for a longer period of time or even continuously for several days. The advantage of using a sorbent unit and a mixing bag is particularly interesting since only a small amount of fluid is needed (e.g. 5 liters instead of 60 to120 liters).

Referring now to figure 1 1 , this embodiment is designed to perform a back- filtration mode. The back-filtration mode allows pushing dialysate solution into the dialyzer so that water and potentially a part of elements of the dialysate solution passes through the membrane from the dialysate part to the blood part. In this embodiment, the cassette (59) comprises fluidic pathways of dialysate which may be at least in part a closed fluid path.

The blood of the patient flows into the blood line (57, 58) and through the dialyzer (50). The blood may be conveyed by a blood pump from the blood line 57 to the blood line 58. The blood line may flow in the same cassette of dialysate cassette (59). The dialysate solution is conveyed by a single pumping means (60) (for instance a single peristaltic pump). The dialysis system may comprise a pump actuator (not show) designed to cooperate with the cassette (59) and the pumping means (60). The system comprises several fluidic pathways and valves so that the pumping means may be a unidirectional pump. The system may comprise a regeneration system as disclosed above, said regeneration system comprises an additive bag (55), a dedicated valve V2' and may use the same single pumping means of the dialysate solution. The system may comprise several sensor (temperature sensor, ...), for example the sensor S1 may be a blood sensor, S2 an air sensor, S3 a ammonia sensor, S4 a conductivity sensor, a scale (53). Some pressure sensors may be arranged in the system so that control the pressure of the dialysate solution into the different elements and/or into the fluid pathways.

In the embodiment of the figure 1 1 , the cassette (59) is arranged to pull or push a dialysate solution from or to the dialyzer (50) so that the system can perform diffusion and/or convective clearance as well as a back-filtration. In other terms, the system is able to produce a positive or a negative pressure in the dialysate side of the dialyzer compare to the blood side in such a way to improve the quality of the treatment by ensuring a proper fluid balance on the patient side. The pressure in the dialysate part of the dialyzer may be determined depending on the operating mode (push or pull the dialysate solution to or from the dialyzer), the flow rate of the pumping means and the fluidic resistance of the sorbent device, the dialyzer and/or a proportional valve. In a preferred embodiment, the pressure is monitored at various places in the system to ensure a proper functioning of each phase. An essential component of the invention to perform such back- filtration results from the use of the sorbent device which creates a significant fluidic resistance necessary to create the positive pressure needed on the dialysate side of the filter.

During a hemodialysis treatment, the system removes a determined amount of ultrafiltration and/or hemofiltration but some elements (such as water) should not be removed beyond a certain speed. Thus, the system is designed to control the treatment and perform different operating mode: ultrafiltration mode (or convective mode), diffusion mode and back-filtration mode. During the treatment the system can change the mode in such a way to perform one or more phases which may be ultrafiltration phase, diffusion phase, back-filtration phase or regeneration phase. Preferably each of such phases shall be alternated in order to maintain a physiological blood pressure on the patient side (so as to avoid modifying the patient blood water content too rapidly over time). The goal, however, remains to eliminate a certain amount of water from the patient over the entire treatment time, as much as possible on a regular or pre-determined basis.

To perform a haemodialysis phase, the valves V1 ', Ml' and V8' are open and the valves V2', V3', A', V5', V6' and V9' are closed (may be automatically controlled by a processor of the system). The dialysate is conveyed by the pump optionally through a closed fluid path. The pump pulls the dialysate solution from the mixing bag (54) and through the dialyzer (50) and pushes against the sorbent device (51 ), flows through an optional heater (52) and reaches the mixing bag (54).

To perform an ultrafiltration phase, the valves V1 ' and MT are open and the valves V2', V3', MA', V5', V6', V8" (optionally) and V9" are closed (may be automatically controlled by a processor of the system). The dialysate is conveyed by the pump, from the dialyzer (50), through the sorbent device (51 ) until the mixing bag (54).

To perform a back-filtration phase, the valves V4', V3' and V5' are open and the valves V1 ', V2', V9', V8', V7' and V6' are closed (may be automatically controlled by a processor of the system). The dialysate is conveyed by the pump optionally through a closed fluid path. The pump pulls the dialysate solution from the mixing bag (54) (without passing through the dialyzer (50)) and pushes against the dialyzer (50), flows through the sorbent device (51 ) which acts as a flow restriction device, through an optional heater (52) and reaches the mixing bag (54). To perform a regeneration phase, the valves V2' and V6' are open and the valves V1 ', V2', V3', MA', V5', MT, V8" and V9" are closed (may be automatically controlled by a processor of the system). The additive is conveyed by the pump form the additive bag (55) to the mixing bag (54) (optionally trough an optional heater (52)). After adding a determined amount of additive in the mixing bag (54), a residual amount of additive may be stored in the fluidic pathway. If this residual amount of additive is conveyed directly to the dialyzer, for example if a back- filtration is performed just after the regeneration phase, the patient may receive too much additive solution. So after a regeneration phase, the system performs a recirculation phase in which the solution is conveyed in a closed fluid path by the pump without passing though the dialyzer (50).

It is also part of the invention to apply the back-filtration in order to sterilize the liquid which is re-injected into the patient by using the filtration properties of the dialyzer.

WATER CONTENT OF THE PATIENT During the treatment, the system has to monitor the water content of the patient because an excessive amount of water should not be removed from the patient. Furthermore, the speed at which the water is removed may be also monitored. Thus, the system comprises means for controlling the removed water and the speed at which it is removed or has been removed.

The devices of the prior art use two distinct bags with dedicated scale, the first bag contains the fresh dialysate and the second bag contains the ultrafiltration and/or hemofiltration. Thus, for monitoring the water content of the patient this device compares the amounts of each bags (first bag before the treatment and second bag after the treatment). Two major drawbacks appear: both scales have to be correctly calibrated and need to have a very good accuracy (but it is very difficult when each bag weighs more than 60 kg). In some cases, both bags are on the same scale, but the total weight is too high to ensure an accurate measurement for small quantities which need to be corrected in the patient fluid balance. Our device uses only one bag in which the fresh dialysate and the ultrafiltration and/or hemofiltration are stored. Indeed, since the system works in a closed loop, a single scale can be used to monitor the water content of the patient. If at the beginning of the treatment, the bag weighs 1 kg and after the treatment the bag weighs 1 .2kg, then the device has removed 0.2 kg of water. In such event, a certain amount of water can be re-injected into the patient via back-filtration and/or pre and/or post filtration (such as in a CRRT mode). The device of the invention has not the drawback of scale calibration because the system just monitors the differential of amount over time during the treatment so that the exact weight is not necessary (as in conventional systems with two scales). Furthermore, our device does not need a lot of fresh dialysate because the dialysate solution is regenerated during the treatment, and our scale can therefore be more accuracy. After a regeneration phase, if the system has injected 0.1 kg of additive in the bag, the new reference measurement is the last reference measurement to which the 0.1 kg will be added. In other terms, since the system works in a closed loop, where the same fluid is regenerated, it is easy to balance the fluid in and out from the patient while limiting the risk of patient over or under fill which would require sophisticated method to prevent harmful potential circumstances. The system preferably monitors the variation of the water content of the patient during the entire treatment and ensures a progressive removal of ultrafiltrate and/or hemofiltrate from the patient. Last, but not least, since the system is a closed loop it is more secured against high variations of body fluid on the patient side (thanks to the weight scale), while reducing the septic contamination risks.