PRODUCTION OF CONCENTRATED SPENT DIALYSATE

Abstract

A concentrated spent dialysate is produced for by reducing electrolytes in a spent dialysate by electrodialysis and de-watering the spent dialysate by a forward osmosis operation.

A hemodialysis treatment apparatus has an ultrafiltration unit for exchange of solutes of a patient's blood plasma and a dialysate, resulting in a stream of cleaned blood for returning to the patient and a stream of spent dialysate. An electrodialysis device reduces electrolytes in the spent dialysate. A forward osmosis unit with a membrane having a feed side and a draw side that is allows only water to permeate. A stream of spent dialysate from the ultrafiltration unit is in fluid communication with the feed side and a stream of concentrated dialysate is in fluid communication with the draw side. A stream of dialysate results. Blood plasma is pumped from the patient to the ultrafiltration unit.

Claims

1. A method for producing a concentrated spent dialysate comprising the steps of; reducing the amount of electrolytes in a spent dialysate by electrodialysis and de-watering the spent dialysate by a forward osmosis operation, in which the spend dialysate is passed through the feed side of a first forward osmosis unit, whereas a concentrated dialysate is passed through the draw side of the first forward osmosis unit producing a diluted concentrated dialysate, which is delivered to a hemodialysis treatment apparatus comprising a dialyzer, optionally after adjustment of the concentration of the components.

2. The method according to claim 1, wherein the amount of electrolytes in the spent dialysate is reduced by at least 20% by the electrodialysis.

3-5. (canceled)

6. The method according to claim 1, wherein the first forward osmosis unit is a first hollow fiber module, which is connected with second or further hollow fiber module(s), such that the partly de-watered spent dialysate solution exiting the feed side of the first hollow fiber module is further de-watered in the feed side of the second or further hollow fiber modules.

7. The method according to claim 6, wherein the concentrated dialysate prior to dilution in the first hollow fiber module has been diluted in second or further hollow fiber module(s).

8. The method according to claim 6, wherein the membrane area of the first membrane module is larger than the membrane area of the second or further membrane module.

9. The method according to claim 8, wherein the first forward osmosis module has a membrane area twice as large as the second or further membrane module(s).

10. The method according to claim 1, wherein the spent dialysate is treated by forward osmosis at a temperature of 30° C. or above.

11. The method according to claim 6, wherein the transmembrane pressure is 1 bar or above.

12. The method according to claim 6, wherein a sodium bicarbonate solution is added to the partly diluted dialysate between the first hollow fiber module and the second or the further hollow fiber module(s), or between the second hollow fiber module and the further hollow fiber module(s).

13. The method according to claim 1, wherein the membrane of the forward osmosis unit comprises aquaporin water channels.

14. Hemodialysis treatment apparatus comprising: a) an ultrafiltration unit allowing for exchange of solutes of a patient's blood plasma and a dialysate, resulting in a stream of cleaned blood for returning to the patient and a stream of spent dialysate; b) an electrodialysis device capable of reducing the amount of electrolytes in the spent dialysate, c) a first forward osmosis unit comprising a membrane having a feed side and a draw side, the membrane being substantially impervious to solutes and essentially allowing only water to permeate, wherein a stream of spent dialysate from the ultrafiltration unit, is in fluid communication with the feed side and a stream of concentrated dialysate is in fluid communication with the draw side, resulting in a stream of dialysate, optionally after adjustment of the concentration of the solutes, for use in the ultrafiltration unit and a stream of concentrated spent dialysate; and d) a pump for pumping blood plasma from the patient to the ultrafiltration unit.

15. Hemodialysis treatment apparatus according to claim 14, wherein the forward osmosis unit is a hollow fiber module.

16. Hemodialysis treatment apparatus according to claim 14, wherein the feed side of the first forward osmosis unit is connected to the feed side of a second or further forward osmosis units, such that the partly de-watered spent dialysate solution exiting the first forward osmosis unit is further de-watered in the feed side of the second or further hollow fiber modules.

17. The hemodialysis treatment apparatus according to claim 1, wherein the first forward osmosis unit has a membrane area twice as large as the second or further membrane module(s).

18. The hemodialysis treatment apparatus according claim 14, further comprising a heater capable of heating the spent dialysate prior to treatment in the forward osmosis unit.

19. The hemodialysis treatment apparatus according to claim 14 comprising a pump configured for providing a transmembrane pressure in the forward osmosis unit of 1 bar or more.

20. The hemodialysis treatment apparatus according to claim 16, wherein a conduit between the first forward osmosis and the second or further osmosis unit(s) is supplemented with a further conduit, which is connected to a source of sodium bicarbonate.

21. The hemodialysis treatment apparatus according to claim 14, further comprising a pump for pumping the concentrated dialysate to the forward osmosis unit, or a pump for suction of the diluted dialysate from the forward osmosis unit.

22. The hemodialysis treatment apparatus according to claim 14, further comprising a mixing device for adjusting the dialysate from the forward osmosis unit with a sodium carbonate solution.

23. The hemodialysis treatment apparatus according to claim 22, further comprising a conductivity sensor after the mixing device for feed-back regulation of the adjustment of the dialysate from the forward osmosis unit with the sodium carbonate solution.

24-33. (canceled)

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0070] In the following detailed portion of the present disclosure, the aspects, embodiments and implementations will be explained in more detail with reference to the example embodiments shown in the drawings, in which:

[0071] FIG. 1 is a schematic representation of the recirculation of water from the spent dialysate to the dialysate.

[0072] FIG. 2 illustrate the experimental setup

[0073] FIG. 3 shows an embodiment of the forward osmosis operation using two modules in series.

[0074] FIG. 4 shows an embodiment of the forward osmosis operation using three modules in series.

[0075] FIG. 5 discloses the provision of the pump at the feed side for providing a transmembrane pressure of the embodiment shown in FIG. 4.

[0076] FIG. 6 discloses the supplementing of the partly diluted draw solution with a sodium bicarbonate solution between the first and the second module of the embodiment shown in FIG. 5

[0077] FIG. 7 shows the provision of a pretreatment of the feed solution to reduce the solute concentration prior to being fed into the first module.

[0078] FIG. 8 shows a flow chart of currently used RO process.

[0079] FIG. 9 discloses a schematic representation of the use of tap water to produce the dialysate.

[0080] FIG. 10 shows a general setup for the use tap water in the production of dialysate.

[0081] FIG. 11 shows a specific setup for the use tap water in the production of dialysate.

[0082] FIG. 12 shows a flow chart of the experiment reported in the examples.

[0083] FIG. 13 shows the experimental results obtained at 60% recovery.

[0084] FIG. 14 shows the feed flow over time for obtaining 60% recovery.

[0085] FIG. 15 shows the permeation and dilution factor over time for obtaining 60% recovery.

[0086] FIG. 16 shows the recovery over time for obtaining 60% recovery.

[0087] FIG. 17 shows the conductivity over time for obtaining 60% recovery.

[0088] FIG. 18 shows the temperature over time for obtaining 60% recovery.

[0089] FIG. 19 shows the conductivity at various dilutions for obtaining 60% recovery.

[0090] FIG. 20 shows the feed flow versus the recovery.

DETAILED DESCRIPTION

[0091] The overall purpose of this present disclosure is to explore the possibility for reducing the amount of water consumption during hemodialysis treatment. Besides saving water being a desired purpose, the reduced usage of water also makes it possible to produce a mobile dialysis treatment apparatus, which will create a better life for the patients.

[0092] The experiments presented herein have shown that it is possible to obtain a reduction of water usage of at least 50% or more, such as at least 60% or more, suitably at least 70% or more, preferably at least 80% or more, and more preferably at least 90% or more. Initial experiments have been conducted on a sodium chloride solution designed to have the same osmotic pressure as real spent dialysate. Subsequent experiments have been performed at a hospital (Rigshospitalet in Denmark) using real spent dialysate. In both instances the water recovery rate was examined. The experiments were conducted on different patients, on patients with different days of rest between treatments and on spent dialysate with different concentrations of waste compounds. Surprisingly, the results obtained based on spent dialysate from patients correlated well with the results obtained for the sodium chloride solution, i.e. the water recovery rates were essentially the same for spent dialysate from patients and the sodium chloride solution.

[0093] By building a setup with three different sized modules, addition of 3 bar transmembrane pressure (TMP) and the addition of sodium bicarbonate during the process, a water recovery of 74% was reached on the sodium chloride solution whereas a recovery rate of 76% was reached at for spent dialysate from patients. A simulated pre-treated spent dialysate experiment reached a recovery on 95%. A water recovery rate above 90% is generally regarded as desirable for a portable solution.

[0094] A mobile or portable hemodialysis treatment apparatus is devised by the present disclosure and the principle is shown in FIG. 1. The portable or mobile system comprises a dialyzer, a forward osmosis unit, and one or more pumps for circulating the fluids. Unless the elements of the portable or mobile system are fully integrated, the system also comprises tubes or hoses for connecting the elements. Notably, the patient's blood is connected through a tube or hose to the inlet of the dialyzer, i.e. the inlet of the ultrafiltration unit. After being dialyzed, the cleaned blood leaves the outlet of the dialyzer and is transported through a tube for delivery to the patent. The dialysate enters the inlet of the dialyzer and exchanges with the blood and the spent dialysate exits the dialyzer at the outlet as spent dialysate. The spent dialysate is transported through a tube from the outlet of the dialyzer to the inlet of a feed compartment of a forward osmosis module in a forward osmosis operation, optionally assisted by a pump. At the outlet of forward osmosis operation, the concentrated spent dialysate exits for further treatment or discharge. An aqueous solution of concentrated dialysate is delivered to the inlet of the draw compartment of the forward osmosis unit. In the forward osmosis unit water is transported over the membrane, thereby concentrating the spent dialysate and diluting the concentrated dialysate. The diluted dialysate exits the forward osmosis operation at an outlet and may be fed directly to the inlet of the dialyzer. However, usually, the diluted dialysate needs to be adjusted by addition of a sodium bicarbonate solution before entering the dialyzer.

[0095] Various types of forward osmosis operations are disclosed in FIGS. 3 to 7. In FIG. 3, the forward osmosis operation comprises two forward osmosis modules arranged in series, i.e. the spent dialysate enters at the left arrow into the feed compartment of a first module. After partly dewatering the partly concentrated spent dialysate is transported to the feed compartment of a second module. In a preferred embodiment. Hollow fiber modules are used in the forward osmosis operation. While hollow fiber modules of the same size may be used, it is not necessary that the second module is of a similar size as a part of the water has been removed. The arrow at the right-handed side of the figure illustrates the introduction of a concentrated dialysate to the shell side of the second hollow fiber module. After the concentrated dialysate has been diluted in the second hollow fiber module, the partly diluted concentrated dialysate leaves at an outlet. The partly diluted concentrated dialysate is transported to the inlet of the first module for further dilution and the diluted dialysate exits at an outlet in the other end of the module.

[0096] FIG. 4 shows a further development of the embodiment shown in FIG. 3. In the further development, a third forward osmosis module has been provided in series, such that the partly concentrated spent dialysate leaving the second module is transported to the feed side inlet of the second module. After being treated in the third forward osmosis module, the concentrated spent dialysate is discharged. The draw solution, i.e. the concentrated dialysate, enters at the inlet of the third module at the arrow on the right-handed side of the figure. The partly diluted dialysate is, after treatment in the third forward osmosis module, transported to the inlet of the second module and treated as indicated above.

[0097] FIG. 5 shows a further development of the embodiment of FIG. 4, in which a pump is supplying the spent dialysate with a hydrostatic pressure before the spent dialysate enters the inlet of the first module.

[0098] FIG. 6 illustrates a further development of the embodiment of FIG. 5, in which a solution of sodium bicarbonate and optional further salts are added to the partly diluted dialysate before entering the inlet of the first module.

[0099] FIG. 7 illustrates a further development of the embodiment of FIG. 6, in which the spent dialysate prior to being pumped into the feed compartment of the first osmosis unit is subjected to a pretreatment to remove a part of the electrolytes. The pretreatment may be conducted in an electrodialysis device.

EXAMPLES

Example 1 (Comparative)

[0100] An experimental test set up was prepared as indicated in WO 2015/124716. A HFFO2 forward osmosis module (membrane area: 2.3 m.sup.2) available from Aquaporin A/S was used to concentrate spent dialysate by pumping the solution at a velocity of 500 ml/min to the lumen side of the module as illustrated on FIG. 2. The model spent dialysate was prepared by dissolving 228 g sodium chloride in 25 l water corresponding to an osmolarity of 0.27 osmol/kg. Water was drawn by forward osmosis through the membrane by a concentrated electrolyte solution entering the shell side of the module at a velocity of 11 ml/min. The concentrated electrolyte solution was diluted by the water drawn through the membrane and exits as diluted electrolyte solution. The spent dialysate is concentrated by the water being drawn through the membrane and leaves the other side of the fiber of the module as a concentrated dialysate.

[0101] The recovery rate is the percentage of water recovered from the spent dialysate. It is calculated as the permeation or volumetric flux of water drawn though the membrane (ml/min) divided by the volumetric flow of feed (ml/min), i.e. spent dialysate. For practical reasons, the data for calculating the recovery rate was gathered after a certain amount of time has elapsed or a certain amount of spent dialysate was treated in the module.

[0102] At a temperature of 18° C. the recovery rate for the HFFO2 membrane module was calculated as 29.5% as an average of 2 runs.

[0103] By increasing the temperature to 37° C. the recovery rate increased to 36% as an average of 2 runs.

Example 2

[0104] As illustrated in FIG. 3 two modules were used in series as the FO operation in a setup otherwise similar to example 1. Thus, the HFFO2 module and a HFFO.6 module (membrane area 0.6 m.sup.2) available from Aquaporin A/S were positioned in series so that the spent dialysate first enters the lumen side of the HFFO2 module and then directly is fed to the lumen side of the HFFO.6 module.

[0105] The concentrated electrolyte solution, i.e. draw solution, was delivered to the shell side of the modules in counter-current with the feed solution. Thus, the concentrated electrolyte solution was first entered into the shell side of the HFFO.6 module for partial dilution and then into the shell side of the HFFO2 module to obtain the diluted electrolyte solution.

[0106] As the average of two runs, the recovery rate was calculated as 32%. The experiments were run at a temperature of 18.5° C.

Example 3

[0107] As illustrated in FIG. 4 three hollow fiber modules were used in series in a set up otherwise similar to example 1. Thus, a HFFO2 module, a HFFO.6 module, and a HFFO.3 module (membrane area: 0.6 m.sup.2) available from Aquaporin A/S were positioned in series so that the spent dialysate first enters the lumen side of the HFFO2 module, then directly is fed to the lumen side of the HFFO.6 module, and finally conveyed to the lumen side of the HFFO.3 module.

[0108] The concentrated electrolyte solution, i.e. draw solution, was delivered to the shell side of the modules in counter-current with the feed solution. Thus, the concentrated electrolyte solution was first entered into the shell side of the HFFO.3 module for partial dilution, and then into the shell side of the HFFO.6 module for further dilution, and then finally into the HFFO2 module to obtain the diluted electrolyte solution.

[0109] As the average of two runs, the recovery rate was calculated as 37%. The experiments were run at a temperature of 18.5° C.

[0110] As the average of two runs, the recovery rate was calculated as 37%. The experiments were run at a temperature of 18.5° C.

[0111] By increasing the temperature to 37° C. the recovery rate increased to 43% as an average of 2 runs.

[0112] The model spent dialysate solution was exchanged with spent dialysate from real patients. At a temperature of 34° C. spent dialysate from 3 patients were tested. In average the recovery rate was 45%, i.e. in agreement with the results obtained for the model spent dialysate solution.

Example 4

[0113] The set up using 3 modules in series applied in example 3, was provided with a transmembrane pressure (TMP) to investigate the possible effect on the recovery rate. The system is illustrated in FIG. 5.

[0114] Based on 2 runs, a recovery rate of 51% was obtained when a transmembrane pressure of 1 bar was applied at a temperature of 37° C. When the transmembrane pressure was increased to 3 bar the recovery rate increased to 66%.

[0115] The model spent dialysate solution was exchanged with spent dialysate from real patients. At a temperature of 34 degrees Celsius spent dialysate from 3 patients were tested, applying a transmembrane pressure of 3 bar. In average the recovery rate was 66%, i.e. in agreement with the results obtained for the model spent dialysate solution.

Example 5

[0116] The setup used in examples 3 and 4 was further changed by supplementing the system with addition of 15 ml/min sodium bicarbonate as shown in FIG. 6. Thus, the tube between the HFFO.6 and the HFFO2 module was interrupted by a valve allowing for the addition of the sodium bicarbonate solution.

[0117] The experiments showed a recovery rate of 74% as the average of 2 runs conducted at a temperature of 37° C. and a TMP of 3 bar.

[0118] The model spent dialysate solution was exchanged with spent dialysate from real patients. At a temperature of 34 degrees Celsius spent dialysate from 3 patients were tested, applying a transmembrane pressure of 3 bar and addition of sodium bicarbonate (15 mg/min). In average the recovery rate was 75%, i.e. in agreement with the results obtained for the model spent dialysate solution.

Example 6

[0119] A pretreatment was performed on the model spent dialysate using electrodialysis as illustrated in FIG. 7. By the pretreatment, the amount of electrolytes was reduced around 50%, i.e. to an osmolarity of 0.133 osmol/kg.

[0120] The pretreated spent dialysate was used in the set up of example 5 at a temperature of 36.5° C., applying a transmembrane pressure of 3 bar and addition of sodium bicarbonate (15 mg/min). The experiments showed a recovery rate of 95% as the average of 2 runs.

Example 7

[0121] The experiment of example 6 was repeated using a simulated spent dialysate pretreated with electrodialysis. The simulated spent dialysate was obtained by mixing 10 liter of real spent dialysate from Rigshospitalet with 10 liter of warm RO water.

[0122] An experimental setup similar to example 5 and 6 was applied using a temperature of the spent dialysate of 35° C. to 42° C. and a feed rate of 500 ml/min. The feed and draw pumps were turned on and the valve was adjusted to create a TMP on 3 bar. The addition of sodium bicarbonate was performed at a flow rate of 15 mg/min. The experiments showed a recovery rate of 90%±2% as the average of 2 runs.

Example 8

[0123] The general experimental setup for using tap water as a water source is shown in FIG. 10 and FIG. 11.

[0124] Experiments on 500 ppm and 2000 ppm NaCl solutions were conducted with a recovery of 60% and 80% and a theoretical feed flow of 790 ml/min and 592.5 ml/min feed flow rate, respectively. The 500 ppm NaCl solution consists of 15 g NaCl and 30 l RO water; the 2000 ppm NaCl solution consists of 60 g NaCl in 30 l RO water.

[0125] Screening for precipitation was performed on tap water to determine how recovery, conductivity and dilution rate affects complete hemodialysis sessions.

[0126] The purity of the diluted dialysate with a dilution ratio of 1:35 and 1:45 for the first and second solutions, respectively, before mixing with the pure sodium bicarbonate concentration is checked by using a conductivity meter. Standard dialysate conductivity of the concentrated acid should be between 12-16 mS/cm at 37° C. and 500 ml/min flow rate.

[0127] The experimental conductivity is measured (FIGS. 19 and 20) and a theoretical conductivity is calculated for the two dilutions of 1:35 and 1:45 (as explained above) and RO water.

[0128] A ppm validation was performed to test the quality of tap water in Kongens Lyngby and compared with the RO water used. The theoretical ppm of spent dialysate and the pre-treated spent dialysate was found by converting the concentration used for the simulated spent dialysate solutions to ppm.

[0129] The ppm validation results as well as comparisons of the osmolalities and concentrations of different solutions used is summarized in Table 1.

TABLE-US-00001 TABLE 1 The ppm validation as well as comparison of the osmolalities and concentrations of the different solutions used. Theoretical Experimental Osmolality Concentration Solution ppm ppm [osm/L] [g/L] Spent 9300 9760 0.270 9.3 dialysate Pretreated 4650 5030 0.143 4.65 spent dialysate Simulated 2000 1940 0.062 2.0 tap water 500 456 0.016 0.5 Tap water — 308 0.010 — DK RO water — 40 −0.002 —

[0130] By comparing the experimental and theoretical conductivity it is realized that there has been a negligible diffusion between the salts in the feed and draw solution.

Example 9

[0131] Experiments on 500 ppm NaCl and 2000 ppm NaCl solutions and tap water with a recovery of 60% and 80% were conducted to identify the ideal TMP values and the feed pump RPMs for the experiments.

[0132] The ideal settings for the feed pump RMP and the TMPs are tabulated in Table 2.

TABLE-US-00002 TABLE 2 The settings of the feed pump and the addition of TMP during each of the experiments, which has been found through screenings. Pump flow 60% recovery Pump flow 80% recovery Feed pump RPM TMP Feed pump RPM TMP Solution [min.sup.−1] [bar] [min.sup.−1] [bar]  500 ppm 1285 1 1235 1.8 2000 ppm 1593 3 1528 3.9 Tap water 1675 3.4 1580 4

[0133] The data in the table shows that the permeation target and the recovery target of the 500 ppm and 2000 ppm NaCl solutions are very close to the desired permeation of 474 ml/min for the 60% recovery and the 474 ml/min for the 80% recovery.

Example 10

[0134] An experiment was conducted to determine if the permeation of 474 ml/min and the desired dilution rate of 1:45 for tap water with up to 2000 ppm of NaCl is observed during an FO process with a target recovery of 60%.

[0135] The results are tabulated in Table 3.

TABLE-US-00003 TABLE 3 The results of the experiments conducted on 500 ppm and 2000 ppm NaCl solutions with a 60% recovery, n = 2. Exp. Theo. Feed in Draw out Permeation Recovery Conduc. Conduc. Dilution Solution [ml/min] [ml/min] [ml/min] [%] [mS/cm] [mS/cm] rate  500 ppm 792.5 ± 0.5 480 ± 1 468.5 ± 1.5 59 ± 0 13.55 ± 0.05 12.23 1:45 2000 ppm 784.5 ± 1.5 492.5 ± 2.5 481 ± 3 61.5 ± 0.5 13.55 ± 0.15 11.56 1:46 Target 790 485 474 60 12-18 12-18 1:45

[0136] A additional experiment was conducted to determine if the permeation of 474 ml/min and the desired dilution rate of 1:45 for tap water with up to 2000 ppm of NaCl is observed during an FO process with a target recovery of 80%.

[0137] The results are tabulated in Table 4.

TABLE-US-00004 TABLE 4 The results of the experiments conducted on 500 ppm and 2000 ppm NaCl solutions with a 80% recovery, n = 2. Exp. Theo. Feed in Draw out Permeation Recovery Conduc. Conduc. Dilution Solution [ml/min] [ml/min] [ml/min] [%] [mS/cm] [mS/cm] rate  500 ppm 593.5 ± 0.5 485.5 ± 3.5 473.5 ± 3.5 80.5 ± 0.5 13.7 ± 0.1 11.94 1:46 2000 ppm 589.5 ± 0.5 492 ± 3 470 ± 3 82 ± 1 13.55 ± 0.15 11.59 1:46 Target 592.5 485 474 80 12-18 12-18 1:45

[0138] The results for both 60% and 80% are within a reasonable range of the target value.

Example 11

[0139] A range of recovery values were tested from 20% to 90% recovery using tap water over 5 mins of running time for each recovery values and the results are tabulated FIG. 20.

[0140] The data shows no scaling or plugging of the membrane during the screening; hence it is concluded that experiments can be run at all recoveries.

Example 12

[0141] Experiments on tap water were conducted with a continuous flow of tap water through the system to determine the possibility of running a FO process for a complete hemodialysis treatment session without precipitation (FIG. 13 to FIG. 18).

[0142] Measurements were taken in 10 mins intervals over 210 minutes of running time. The experimental results are a bit lower than the desired 60% recovery (FIG. 13), however, within the accepted the target range and proves the viability of using an FO process during the entire duration of a hemodialysis treatment. The conductivity (FIG. 17) and temperature (FIG. 18) of the experiments stayed within the accepted target rang throughout the duration of the experiments.

[0143] The feed flow (FIG. 14) was also measured at 3.4 bar pressure and it was concluded that the targeted feed flow is slightly lower than the target feed flow of 11 ml/min. Permeation and dilution factor study results (FIG. 15) over time show that while the permeation is not high enough to obtain a dilution ratio of 1:45, it is still within the recommended range of ratio of 1:35 to 1:45. Hence, while the permeation and recovery (FIG. 16) is lower than desired, the FO process is still viable for use for hemodialysis treatment.