U.S. patent application number 13/757792 was filed with the patent office on 2014-06-12 for ph and buffer management system for hemodialysis systems.
This patent application is currently assigned to Medtronic, Inc.. The applicant listed for this patent is Martin T. Gerber, David B. Lura, Thomas E. Meyer, Bryant J. PUDIL. Invention is credited to Martin T. Gerber, David B. Lura, Thomas E. Meyer, Bryant J. PUDIL.
Application Number | 20140158588 13/757792 |
Document ID | / |
Family ID | 50879788 |
Filed Date | 2014-06-12 |
United States Patent
Application |
20140158588 |
Kind Code |
A1 |
PUDIL; Bryant J. ; et
al. |
June 12, 2014 |
pH AND BUFFER MANAGEMENT SYSTEM FOR HEMODIALYSIS SYSTEMS
Abstract
Systems and methods for managing the pH of a dialysate fluid
during hemodialysis therapy. The systems and methods adjust
dialysate pH and buffer concentration to generate a predetermined
total bicarbonate buffer concentration in a dialysate entering a
dialyzer.
Inventors: |
PUDIL; Bryant J.; (Plymouth,
MN) ; Gerber; Martin T.; (Maple Grove, MN) ;
Lura; David B.; (Maple Grove, MN) ; Meyer; Thomas
E.; (Stillwater, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
PUDIL; Bryant J.
Gerber; Martin T.
Lura; David B.
Meyer; Thomas E. |
Plymouth
Maple Grove
Maple Grove
Stillwater |
MN
MN
MN
MN |
US
US
US
US |
|
|
Assignee: |
Medtronic, Inc.
Minneapolis
MN
|
Family ID: |
50879788 |
Appl. No.: |
13/757792 |
Filed: |
February 2, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61735380 |
Dec 10, 2012 |
|
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Current U.S.
Class: |
210/96.2 ;
210/195.2 |
Current CPC
Class: |
A61M 1/3437 20140204;
A61M 1/3413 20130101; A61M 1/165 20140204; A61M 2205/50 20130101;
A61M 1/1605 20140204; A61M 2205/3324 20130101; A61M 1/3406
20140204; A61M 1/1696 20130101; A61M 1/287 20130101; A61M 1/16
20130101; A61M 2205/33 20130101; A61M 1/34 20130101 |
Class at
Publication: |
210/96.2 ;
210/195.2 |
International
Class: |
A61M 1/16 20060101
A61M001/16 |
Claims
1. A system for infusing a buffer into a dialysate, comprising: a
dialysate flow loop for circulating a dialysate through a dialyzer,
wherein acid or base equivalents are added to the dialysate during
operation of the dialysate flow loop; a urea sensor that measures
or allows for the calculation of urea content of the dialysate in
at least one portion of the dialysate flow loop; an infusate system
configured to add a bicarbonate buffer component or unbuffered
sodium bicarbonate to the dialysate; and a controller for
controlling an amount of the bicarbonate buffer component or
unbuffered sodium bicarbonate for addition to the dialysate to
generate a predetermined total bicarbonate buffer concentration in
the dialysate entering the dialyzer.
2. The system of claim 1, wherein the system further comprises a
dialysate regeneration unit, the dialysate regeneration unit for
removing a waste species from the dialysate.
3. The system of claim 2, wherein the dialysate regeneration unit
contains urease for converting urea to ammonium carbonate.
4. The system of claim 2, wherein the dialysate regeneration unit
modifies the total bicarbonate buffer concentration of the
dialysate entering the dialysate regeneration unit or modifies the
pH of the dialysate entering the dialysate regeneration unit.
5. The system of claim 4, wherein the dialysate exiting the
dialysate regeneration unit comprises a concentration of
bicarbonate buffer that is less than the predetermined total
bicarbonate buffer concentration.
6. The system of claim 1, wherein the controller determines the
total bicarbonate buffer concentration of the dialysate in a first
portion of the dialysate flow loop based at least in part upon a
urea concentration of the dialysate in a second portion of the
dialysate flow loop.
7. The system of claim 1, wherein the controller controls a pH of
the dialysate in a first portion of the dialysate flow loop based
at least in part upon a urea concentration of the dialysate in a
second portion of the dialysate flow loop.
8. The system of claim 6, wherein the system further comprises a
dialysate regeneration unit, the dialysate regeneration unit for
removing a waste species from the dialysate and releasing a
bicarbonate buffer component, unbuffered sodium bicarbonate, carbon
dioxide or combinations thereof to the dialysate.
9. The system of claim 6, wherein the second portion of the
dialysate flow loop is between an outlet of the dialyzer and an
inlet of the dialysate regeneration unit and the first portion of
the dialysate flow loop is between an outlet of the dialysate
regeneration unit and an inlet of the dialyzer.
10. The system of claim 6, wherein the controller determines a
total buffer concentration in the first portion of the dialysate
flow loop and operates the infusate system at a rate to add a
bicarbonate buffer component or unbuffered sodium bicarbonate to
the dialysate to generate dialysate having the predetermined total
bicarbonate buffer concentration.
11. The system of claim 1, further comprising a pH-buffer sensor
for determining a bicarbonate ion concentration and a pH of the
dialysate in at least one point of the dialysate flow loop.
12. The system of claim 11, wherein information from the pH-buffer
sensor is used to determine the amount of bicarbonate buffer
component or unbuffered sodium bicarbonate added by the infusate
system.
13. A system for modifying a pH of a dialysate, comprising: a
dialysate flow loop for circulating a dialysate through a dialyzer,
wherein acid or base equivalents are added to the dialysate during
operation of the dialysate flow loop; a pH-buffer management system
for adding or generating a pH-buffer modifying solution to the
dialysate, wherein the pH-buffer management solution has a
different pH from the dialysate; and a controller for calculating
an amount of the pH-buffer modifying solution for addition to the
dialysate to adjust the dialysate to be of a predetermined pH and
bicarbonate buffer concentration.
14. The system of claim 13, wherein the controller determines the
pH and bicarbonate buffer concentration of a dialysate in a first
portion of the dialysate flow loop based at least in part upon a
urea content of the dialysate in a second portion of the dialysate
flow loop.
15. The system of claim 13, further comprising a urea sensor that
measures or allows for the calculation of urea content of the
dialysate in at least one portion of the dialysate flow loop.
16. The system of claim 13, wherein the dialysate comprises a
bicarbonate buffer component or unbuffered sodium bicarbonate.
17. The system of claim 14, wherein the pH-buffer management system
generates the pH-buffer modifying solution from a feed solution,
and the pH-buffer management system does not substantially modify
the total bicarbonate buffer concentration of the feed
solution.
18. The system of claim 11, wherein the pH-buffer management system
comprises a bipolar electrodialysis system.
19. The system of claim 18, wherein the bipolar electrodialysis
system comprises an anode, a cathode, a first flow channel and a
second flow channel, and a feed solution flowing through the first
flow channel generates the pH-buffer modifying solution.
20. The system of claim 19, further comprising a cation exchange
membrane interposed between the first flow channel and the second
flow channel, a first bipolar membrane interposed between the first
flow channel and the anode and a second bipolar membrane interposed
between the second flow channel and the cathode, wherein the first
and second bipolar membranes comprise a cation exchange membrane
and an anion exchange membrane.
21. The system of claim 20, wherein the cation exchange membrane of
the first bipolar membrane is oriented toward the first flow
channel and an anion exchange membrane of the second bipolar
membrane is oriented toward the second flow channel.
22. The system of claim 19, wherein a base concentrate is generated
from a fluid flowing through the second flow channel during
operation of the bipolar electrodialysis system.
23. The system of claim 22, wherein the base concentrate is
circulated through the second flow channel using a base concentrate
reservoir and a base concentrate pump.
24. The system of claim 13, wherein the pH-buffer management system
comprises a pump to deliver an acid solution as the pH-buffer
modifying solution with the proviso that the acid solution does not
comprise a substantial amount of a bicarbonate buffer component or
an unbuffered sodium bicarbonate.
25. The system of claim 24, wherein the acid solution comprises
hydrochloric acid, phosphoric acid, acetic acid or citric acid.
26. The system of claim 1, wherein the system is controlled
compliant.
27. The system of claim 1, wherein the system selectively meters
fluid into and out of the dialysate flow loop.
28. The system of claim 1, wherein the system selectively meters
fluid into and out of the dialysate flow loop using any one of a
control pump, a water pump, a salination pump, an acid concentrate
pump, a replacement fluid pump, and combinations thereof.
29. The system of claim 1, wherein the system provides for
bi-directional flow.
30. The system of claim 13, wherein the system is controlled
compliant.
31. The system of claim 13, wherein the system selectively meters
fluid into and out of the dialysate flow loop.
32. The system of claim 13, wherein the system selectively meters
fluid into and out of the dialysate flow loop using any one of a
control pump, a water pump, a salination pump, an acid concentrate
pump, a replacement fluid pump, and combinations thereof.
33. The system of claim 13, wherein the system provides for
bi-directional flow.
Description
FIELD OF THE INVENTION
[0001] The invention relates to systems and methods for managing
the pH of a dialysate fluid during hemodialysis therapy. The
invention adjusts dialysate pH and buffer concentration to generate
a predetermined total bicarbonate buffer concentration in a
dialysate entering a dialyzer.
BACKGROUND
[0002] During hemodialysis, the dialysate pH and buffer
concentration play a critical role in patient outcomes. The
dialysate pH and buffer concentration are specified for a patient
based on the acid-base status of the patient. Acidotic patients can
be treated by increasing their bicarbonate buffer levels and
patients with alkalosis can be treated by decreasing their
bicarbonate levels. A method to manage pH and buffer dialysate
concentration is especially important with systems that contain a
component that may change the pH level and bicarbonate
concentration to unknown values. For example, regenerative
hemodialysis systems, such as the Recirculating Dialysate System
("REDY" System), contain sorbent materials that release and/or
remove hydrogen ions and bicarbonate from the dialysate fluid. The
removal and/or addition of hydrogen ions and bicarbonate to the
dialysate fluid depend on several factors including: patient blood
urea level, patient weight, dialysate composition, sorbent
properties, etc. Because of this, it becomes difficult to predict
the changes in dialysate pH and bicarbonate concentration that will
occur during a hemodialysis session. Therefore, there is a need for
systems and methods that can control the pH and bicarbonate
concentration of the dialysate. There is also a need for systems
and methods for managing pH and bicarbonate that minimize system
size and weight and do not require large amounts of fluid.
SUMMARY OF THE INVENTION
[0003] The invention is directed toward a system having a dialysate
flow loop for circulating a dialysate through a dialyzer wherein
acid or base equivalents are added to the dialysate during
operation of the dialysate flow loop and a urea sensor that
measures or allows for the calculation of urea content of the
dialysate in at least one portion of the dialysate flow loop, and
an infusate system wherein the infusate system can be configured to
add a bicarbonate buffer component to the dialysate. In any
embodiment, the infusate system can be configured to add unbuffered
sodium bicarbonate. The system also can use a controller for
calculating an amount of the bicarbonate buffer component for
addition to the dialysate to generate a predetermined total
bicarbonate buffer concentration in the dialysate entering the
dialyzer.
[0004] In any embodiment, a urea sensor can be provided to allow
for the determination of the urea content of a dialysate flowing to
a dialysate regeneration unit. A controller can be provided having
a processor to determine the bicarbonate buffer composition of a
dialysate resulting from removal of urea content from the dialysate
by contacting or processing with the dialysate regeneration unit
and can also optionally include a sodium management system for
adjusting the sodium ion concentration of the dialysate. Moreover,
in any embodiment, the determination of the bicarbonate buffer
composition can allow for a controlled amount of bicarbonate buffer
to be added to the dialysate to form a dialysate with a
predetermined concentration of a bicarbonate buffer prior to use in
the dialyzer.
[0005] In any embodiment, the system for infusing a buffer into a
dialysate can be controlled compliant. In any embodiment, the
system for infusing a buffer into a dialysate can selectively
meters fluid into and out of the dialysate flow loop. In any
embodiment, the system for infusing a buffer into a dialysate can
selectively meters fluid into and out of the dialysate flow loop
using any one of a control pump, a water pump, a salination pump,
an acid concentrate pump, a replacement fluid pump, and
combinations thereof. In any embodiment the system for infusing a
buffer into a dialysate can provide for bi-directional flow.
[0006] A system for modifying a pH of a dialysate is also provided
having a dialysate flow loop for circulating a dialysate through a
dialyzer wherein acid or base equivalents can be added to the
dialysate during operation of the dialysate flow loop. The system
also can optionally utilize a urea sensor that measures or allows
for the calculation of urea content of the dialysate in at least
one portion of the dialysate flow loop; a pH-buffer management
system for adding or generating a pH-buffer modifying solution to
the dialysate wherein the pH-buffer management solution has a
different pH from the dialysate; and a controller for calculating
an amount of the pH-buffer modifying solution for addition to the
dialysate to adjust the dialysate to a predetermined pH
[0007] In any embodiment, a controller can receive data from a pH
sensor for the pH of a dialysate in a first portion of the
dialysate flow loop. In other embodiments, a controller can receive
data from a urea sensor based at least in part upon a urea content
of the dialysate in a second portion of the dialysate flow loop. In
certain embodiments, the controller can receive data from both the
pH and urea sensor. Having received information on the pH and urea
concentration from either or both of the pH and/or urea sensors,
the controller can provide instructions to the pH-buffer management
system or the infusion system for any necessary adjustments to the
dialysate bicarbonate concentration.
[0008] In any embodiment, a system for modifying a pH of a
dialysate can utilize a dialysate flow loop for circulating a
dialysate through a dialyzer, wherein acid or base equivalents are
added to the dialysate during operation of the dialysate flow loop.
A urea sensor measures or allows for the calculation of urea
content of the dialysate in at least one portion of the dialysate
flow loop. A pH-buffer management system adds or generates a
pH-buffer modifying solution to the dialysate, wherein the
pH-buffer modifying solution has a different pH from the dialysate,
and a controller for calculates an amount of the pH-buffer
modifying solution for addition to the dialysate to adjust the
dialysate to a predetermined pH and bicarbonate concentration.
[0009] In any embodiment, a controller controls the bicarbonate
concentration of a dialysate in a first portion of the dialysate
flow loop based at least in part upon a urea content of the
dialysate in a second portion of the dialysate flow loop.
[0010] In any embodiment, the system for modifying a pH of a
dialysate can be controlled compliant. In any embodiment, the
system for modifying a pH of a dialsyate can selectively meters
fluid into and out of the dialysate flow loop. In any embodiment,
the system for modifying a pH of a dialysate can selectively meters
fluid into and out of the dialysate flow loop using any one of a
control pump, water pump, a salination pump, an acid concentrate
pump, a replacement fluid pump and combinations thereof. In any
embodiment the system for modifying a pH of a dialysate can Provide
for bi-directional flow.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a flow diagram of a dialysate regeneration system
with a controlled compliant dialysate circuit and a pH and buffer
management system.
[0012] FIG. 2 is a flow diagram of a dialysate regeneration system
with a controlled compliant dialysate circuit and a pH and buffer
management system with a by-pass.
[0013] FIG. 3 is a flow diagram of a dialysate regeneration system
with an open, non-fixed volume dialysate circuit and a pH and
buffer management system.
[0014] FIG. 4 is a flow diagram of a dialysate regeneration system
with a controlled compliant dialysate circuit and a pH and buffer
management system utilizing ultrafiltrate waste to generate a pH
and buffer modifying fluid delivered before a dialysate
regeneration unit.
[0015] FIG. 5 is a flow diagram of a dialysate regeneration system
with a controlled compliant dialysate circuit and a pH and buffer
management system utilizing ultrafiltrate waste to generate a pH
and buffer modifying fluid delivered after a dialysate regeneration
unit.
[0016] FIG. 6 is a flow diagram of a dialysate regeneration system
with an open, non-fixed volume dialysate circuit and a pH and
buffer management system utilizing dialysate from a dialysate
reservoir to generate a pH and buffer modifying fluid delivered
after a dialysate regeneration unit.
[0017] FIG. 7 is a flow diagram of a pH and buffer management
system consisting of a bipolar electrodialysis cell with base
concentrate and electrode rinse flow loops and dialysate or
ultrafiltrate waste inlet and outlet diluate acid streams.
[0018] FIG. 8 is a flow diagram of a two-compartment, single unit
bipolar electrodialysis cell containing bipolar membranes and a
cation exchange membrane.
[0019] FIG. 9A is a flow diagram of a pH and buffer management
system consisting of two bipolar electrodialysis cells in series,
one with base concentrate and electrode rinse flow loops and one
with acid concentrate and electrode rinse flow loops and dialysate
or ultrafiltrate waste inlet and outlet streams.
[0020] FIG. 9B is a flow diagram of a pH and buffer management
system consisting of two bipolar electrodialysis cells in series
with a shared concentrate flow loop, individual electrode rinse
flow loops, and dialysate or ultrafiltrate waste inlet and outlet
streams.
[0021] FIG. 10 is a flow diagram of a two-compartment, single unit
bipolar electrodialysis cell containing bipolar membranes and an
anion exchange membrane.
[0022] FIG. 11 is a flow diagram of a pH and buffer management
system consisting of a three-compartment bipolar electrodialysis
cell with acid concentrate, base concentrate and electrode rinse
flow loops and dialysate or ultrafiltrate waste inlet and outlet
streams.
[0023] FIG. 12 is a flow diagram of a three-compartment, single
unit bipolar electrodialysis cell having bipolar membranes, cation
exchange membranes and anion exchange membranes.
[0024] FIG. 13 is a flow diagram of a hemofiltration regeneration
system with a closed, fixed-volume filtration circuit and a pH and
buffer management system.
[0025] FIG. 14 is a flow diagram of a hemodiafiltration
regeneration system with a closed, fixed-volume diafiltration
circuit and a pH and buffer management system.
[0026] FIG. 15 is a flow diagram of a peritoneal dialysate
regeneration system and a pH and buffer management system.
[0027] Throughout the figures and the specification, components
with the same numbers in the FIG.'s refer to the same
components.
DETAILED DESCRIPTION
Definitions
[0028] Unless defined otherwise, all technical and scientific terms
used herein generally have the same meaning as commonly understood
by one of ordinary skill in the relevant art. The definitions
provided herein should not be rigidly construed without taking into
account the context and other ascribed meanings provided, or by
their use, in other parts of the specification, claims, and
drawings.
[0029] The articles "a" and "an" are used herein to refer to one or
to more than one (i.e., to at least one) of the grammatical object
of the article. By way of example, "an element" means one element
or more than one element.
[0030] The term "acid or base equivalents" refers to an equivalent
acid or base donating or accepting an equal number of moles of
hydrogen or hydronium ions per mole of the acid to which the
equivalent acid is being equated, or mole of hydroxide ions to
which the equivalent base is being equated.
[0031] The term "cation infusate pump" historically known as an
"acid concentrate pump" in dialysis systems refers to a pump that
serves the function to move or control the flow of a fluid to
and/or from a reservoir having a substance that contains at least
one cation species, such as calcium, magnesium and potassium ions.
In the present invention, the historically used term of "acid
concentrate pump" is used.
[0032] The term "acid feed" refers a state of fluid communication
that enables an acid solution to be obtained from an acid source
and connected or feed into a receiving source or flow path.
[0033] An "acid" can be either an Arrhenius acid, a Bronsted-Lowry
acid, or a Lewis acid. The Arrhenius acids are substances or fluids
which increase the concentration of hydronium ions (H3O+) in
solution. The Bronsted-Lowry acid is a substance which can act as a
proton donor. Lewis acids are electron-pair acceptors.
[0034] The term "activated carbon" may refer to a porous carbon
material having a surface area greater than 500 m.sup.2 per gram.
Activated carbon can be capable of absorbing several species
including heavy metals such as lead, mercury, arsenic, cadmium,
chromium and thallium among others, oxidants such as chlorine and
chloramines, fluoride ions, and waste species such as phosphate and
certain nitrogen-containing waste species such as creatinine and
uric acid.
[0035] The terms "administering," "administer," "delivering,"
"deliver," "introducing," and "introduce" can be used, in context,
interchangeably to indicate the introduction of water or a
dialysate having an altered concentration of at least one
component, including electrolytes and alkali and/or alkali earth
ions, to a patient in need thereof, and can further mean the
introduction of water, any agent or alkali and/or alkali earth ions
to a dialysate or dialysis circuit where such water, agent or
alkali and/or alkali earth ion will enter the blood of the patient
by diffusion, transversal of a diffusion membrane or other
means.
[0036] The term "air trap" refers to a structure for separating a
gas from a mixture of a gas and a liquid or any other separation
means known in the art. An air trap can include a hydrophobic
membrane for allowing gases to pass and for preventing the passage
of water.
[0037] The term "albumin sieving coefficient" can be used to
describe the amount of albumin that will cross a membrane.
[0038] The terms "ammonia sensing module" and "ammonia detector"
refer to a unit that performs all or part of the function to detect
a predetermined level of, or measure a concentration of, ammonia
and/or ammonium ions in a fluid.
[0039] The term "anion exchange membrane" refers to a positively
charged membrane, which allows negatively charged ions (anions) to
pass through.
[0040] The term "anticoagulant" is a substance that prevents or
delays the clotting of blood, such as heparin, Fragmin.RTM., and
sodium citrate.
[0041] The term "atmospheric pressure" refers to the local pressure
of air in the environment in proximity to the system at the time
that the system is operating.
[0042] The term "base concentrate pump" refers to a device that
performs work on a fluid solution to cause fluid flow to control
the volume transfer of a basic or alkaline solution into a
circuit.
[0043] The term "base concentrate reservoir" refers to a vessel or
container, optionally accessible by a pump that contains a variable
amount of a basic or alkaline fluid solution.
[0044] The term "base module" refers to a basic unit of an
apparatus for hemodialysis, hemodiafiltration, or hemofiltration
that incorporates one or more fluid pathways. Exemplary,
non-limiting components that can be included in the base module
include conduits, valves, pumps, fluid connection ports, sensing
devices, a controller and a user interface. The base module can be
configured to interface with reusable or disposable modules of the
apparatus for hemodialysis, hemodiafiltration, or hemofiltration to
form at least one complete fluid circuit, such as a dialysis,
cleaning, disinfection, priming or blood rinse back circuit.
[0045] A "base" can be either a substance that can accept hydrogen
cations (protons) or more generally, donate a pair of valence
electrons. A soluble base is referred to as an alkali if it
contains and releases hydroxide ions (OH--) quantitatively. The
Bronsted-Lowry theory defines bases as proton (hydrogen ion)
acceptors, while the more general Lewis theory defines bases as
electron pair donors, allowing other Lewis acids than protons to be
included. [1] The Arrhenius bases act as hydroxide anions, which is
strictly applicable only to alkali.
[0046] The term "base feed" refers a state of fluid communication
that enables a base solution to be obtained from a base source and
connected or feed into a receiving source or flow path.
[0047] The term "bicarbonate buffer component" refers to any
composition contain bicarbonate (HCO3-) ion or a conjugate acid of
bicarbonate ion in any amount, proportion or pH of the composition.
The bicarbonate buffering system is an important buffer system in
the acid-base homeostasis of living things, including humans. As a
buffer, it tends to maintain a relatively constant plasma pH and
counteract any force that would alter it. In this system, carbon
dioxide (CO2) combines with water to form carbonic acid (H2CO3),
which in turn rapidly dissociates to form hydrogen ions and
bicarbonate (HCO3-) as shown in the reactions below. The carbon
dioxide-carbonic acid equilibrium is catalyzed by the enzyme
carbonic anhydrase; the carbonic acid-bicarbonate equilibrium is
simple proton dissociation/association and needs no catalyst.
CO.sub.2+H.sub.2O.revreaction.H.sub.2CO.sub.3.revreaction.HCO.sub.3.sup.-
-+H.sup.+
[0048] Any disturbance of the system will be compensated by a shift
in the chemical equilibrium according to Le Chatelier's principle.
For example, if one attempted to acidify the blood by dumping in an
excess of hydrogen ions (acidemia), some of those hydrogen ions
will associate with bicarbonate, forming carbonic acid, resulting
in a smaller net increase of acidity than otherwise.
[0049] The term "bicarbonate buffer concentrate" refers to a
bicarbonate (HCO.sub.3.sup.-) buffer component composition at a
higher concentration than found at normal physiological levels that
can be used to for instants to readjusted the pH of the dialysate
(see also definition of bicarbonate buffer component relating to
its use).
[0050] The term "bicarbonate cartridge" refers to a container that
can be a stand-alone container or alternatively can be integrally
formed with an apparatus for hemodialysis, hemodiafiltration, or
hemofiltration. The bicarbonate cartridge can store a source of
buffering material, such as sodium bicarbonate, and can be
configured to interface with at least one other functional module
found in systems for hemodialysis, hemodiafiltration, or
hemofiltration. For example, the bicarbonate cartridge can contain
at least one fluid pathway and include components such as conduits,
valves, filters or fluid connection ports. The bicarbonate
cartridge can be disposable or be consumable wherein the cartridge
is recharged upon depletion. Specifically, the term "bicarbonate
consumables container" refers to an object or apparatus having or
holding a material in solid and/or solution form that is a source
of bicarbonate, such as sodium bicarbonate, that is depleted during
operation of the system. The object or apparatus may be single use,
or may be replenished and used multiple times, for example, by
refilling the object to replace the consumed material.
[0051] The term "bicarbonate feed" refers to fluid solution
introduced into part of the dialysis or ultrafiltrate system. For
example a "bicarbonate feed" is a conduit that contains a
bicarbonate buffer concentrate that is used to readjust the pH of
the dialysate.
[0052] The term "bidirectional pump" refers to a device configured
to perform work on a fluid to cause the fluid to flow alternatively
in either of two opposing directions.
[0053] A "biocompatible material" is a material that has the
ability to interface with living biological tissues with an
acceptable host response in any of specific medical systems,
methods of treatment or delivery contemplated herein. The
biocompatible material can consist of synthetic, natural or
modified natural polymers intended to contact or interact with the
biological systems during application of any of the inventions
contained herein.
[0054] The term "blood access connection" refers to a junction or
aperture through which the blood of a subject is conveyed to or
from an extracorporeal circuit. Commonly, the blood access
connection is made between a terminal end of a conduit of an
extracorporeal circuit and the terminal end of a catheter or
fistula needle that is distal to the subject receiving therapy. A
subject may have more than one blood access connection when
receiving therapy. In the case of two blood access connections they
can be referred to as an arterial blood access connection and a
venous blood access connection.
[0055] The term "blood solute" refers to a substance dissolved,
suspended, or present in blood or dialysate.
[0056] The term "bolus" refers to an increase (or at times a
decrease) of limited duration in an amount or concentration of one
or more solutes, for example sodium, glucose and potassium, or a
solvent, for example water, such that the concentration of a
solution is changed. The term "bolus" includes delivery of solute
and/or solvent to the dialysate fluid path such that it is
delivered to the blood of a subject via diffusion and/or convection
across a dialysis membrane such that the amount or concentration in
the subject is increased or decreased. A "bolus" may also be
delivered directly to the extracorporeal flow path or the blood of
a subject without first passing through the dialysis membrane.
[0057] The term "buffer conduit flow path" refers to a fluid flow
path in fluid communication with a stored source of a buffering
material, such as bicarbonate.
[0058] The term "buffer source" refers to a stored material, such
as bicarbonate, acetate or lactate that provides buffering.
[0059] The terms "buffer source container" and "buffer source
cartridge" refer to objects that have or hold one or more
materials, in solid and/or solution form, that are a source of
buffering, for example a bicarbonate, a lactate, or acetate; and
the object further having at least one port or opening to allow at
least a portion of the buffering material to be released from the
object during operation of the system.
[0060] The term "blood based solute monitoring system" refers to a
system for monitoring a substance dissolved or suspended or present
in blood or dialysate.
[0061] The term "blood rinse back" refers to returning the blood
from a dialyzer and/or extracorporeal circuit to a subject,
normally at conclusion of a therapy session and prior to
disconnecting or removing the subject's blood access connection or
connections. The procedure can include conveying a physiologically
compatible solution through the extracorporeal circuit to push or
flush the blood from the extracorporeal circuit to the subject via
the subject's blood access connection or connections.
[0062] The terms "bypass circuit" "bypass conduit," "bypass flow
path," "bypass conduit flow path" and "bypass" refer to a component
or collection of components configured or operable to create an
alternate fluid pathway to convey a fluid around one or more other
components of a fluid circuit such that at least a portion of the
fluid does not contact or pass through the one or more other
components. At times the term "shunt" may be used interchangeable
with the term "bypass." When any of the above "bypass" terms listed
in this paragraph are used in context as being part of a controlled
compliant system, then the relevant referenced "bypass" has the
proper characteristics as to operate within a controlled compliant
system as defined herein.
[0063] The term "bypass regulator" refers to a component such as
valve that can determine the amount of fluid that can pass through
a by-pass portion of a fluid circuit.
[0064] The term "cartridge" refers to a compartment or collection
of compartments that contains at least one material used for
operation of the system of the present invention.
[0065] The term "cassette" refers to a grouping of components that
are arranged together for attachment to, or use with the device,
apparatus, or system. One or more components in a cassette can be
any combination of single use, disposable, consumable, replaceable,
or durable items or materials.
[0066] The term "cation exchange membrane" refers to a negatively
charged membrane, which allows positively charged ions (cations) to
pass. By convention, electrical current flows from the anode to the
cathode when a potential is applied to an electrodialysis cell.
Negatively charged anions such as chloride ions are drawn towards
the anode, and positively charged cations such as sodium ions are
drawn towards the cathode.
[0067] The term "cation infusate source" refers to a source from
which cations can be obtained. Examples of cations include, but are
not limited to, calcium, magnesium and potassium. The source can be
a solution containing cations or a dry composition that is hydrated
by the system. The cation infusate source is not limited to cations
and may optionally include other substances to be infused into a
dialysate or replacement fluid, non-limiting examples can be
glucose, dextrose, acetic acid and citric acid.
[0068] The term "cation concentrate reservoir" refers to an object
having or holding a substance that is comprised of at least one
cation, for example calcium, magnesium, or potassium ions.
[0069] The terms "communicate" and "communication" include, but are
not limited to, the connection of system electrical elements,
either directly or remotely, for data transmission among and
between said elements. The terms also include, but are not limited,
to the connection of system fluid elements enabling fluid interface
among and between said elements.
[0070] The terms "conduit," "conduit" or "flow path" refer to a
vessel or passageway having a void volume through which a fluid can
travel or move. A conduit can have a dimension parallel to the
direction of travel of the fluid that is significantly longer than
a dimension orthogonal to the direction of travel of the fluid.
[0071] The term "chronic kidney disease" (CKD) refers to a
condition characterized by the slow loss of kidney function over
time. The most common causes of CKD are high blood pressure,
diabetes, heart disease, and diseases that cause inflammation in
the kidneys. CKD can also be caused by infections or urinary
blockages. If CKD progresses, it can lead to end-stage renal
disease (ESRD), where the kidneys fail to function at a sufficient
level.
[0072] The term "citric acid" refers to an organic acid having the
chemical formula C.sub.6H.sub.80.sub.7, and may include anhydrous
and hydrous forms of the molecule, and aqueous solutions containing
the molecule.
[0073] The term "cleaning and/or disinfection concentrate" refers
to a dry substance, or concentrated solutions containing at least
one material for use in cleaning and/or disinfection of an
apparatus.
[0074] The term "cleaning and/or disinfection solution" refers to a
fluid that is used for the purpose of removing, destroying or
impairing at least a portion of at least one contaminant. The
contaminant may be organic, inorganic or an organism. The fluid may
accomplish the purpose by transmission of thermal energy, by
chemical means, flow friction or any combination thereof.
[0075] The terms "cleaning manifold" and "cleaning and disinfection
manifold" refer to an apparatus that has fluid connection ports and
one or more fluid pathways, or fluid port jumpers, that, when
connected to jumpered ports of a base module, create one or more
pathways for fluid to be conveyed between the jumpered ports of the
base module. A cleaning manifold may be further comprised of
additional elements, for example valves and reservoirs.
[0076] The term "container" as used herein is a receptacle that may
be flexible or inflexible for holding fluid or solid, such as for
example a spent dialysate fluid, or a sodium chloride or sodium
bicarbonate solution or solid.
[0077] The terms "common container," "common cartridge," or "common
reservoir," and the like refer to an object or apparatus that can
hold more than one material; however, the time of holding more than
one material may or may not necessarily be at the same time. The
material(s) may be in solid and/or solution forms and may be held
in separate compartments within the object or apparatus.
[0078] The term "common fluid inlet port" refers to an opening or
aperture through which all fluid first passes to enter an object,
apparatus or assembly.
[0079] The term "common fluid outlet port" refers to an opening or
aperture through which all fluid passes to exit an object,
apparatus or assembly.
[0080] The terms "communicate" and "communication" include, but are
not limited to, the connection of system electrical elements,
either directly or remotely, for data transmission among and
between said elements. The terms also include, but are not limited,
to the connection of system fluid elements enabling fluid interface
among and between said elements.
[0081] The terms "component" and "components" refer to a part or
element of a larger set or system. As used herein, a component may
be an individual element, or it may itself be a grouping of
components that are configured as a set, for example, as a cassette
or a cleaning and/or disinfection manifold.
[0082] The term "comprising" includes, but is not limited to,
whatever follows the word "comprising." Thus, use of the term
indicates that the listed elements are required or mandatory but
that other elements are optional and may or may not be present.
[0083] The term "concentrate pump" refers to a device that can
perform work on a fluid solution to cause the fluid flow and can
actively control the transfer of fluid volume such as an infusate
or an acid concentrate, base concentrate, or buffer concentrate
into a circuit.
[0084] The terms "concentrate flow channel," "concentrate flow
loop," "concentrate stream," refer to a fluid line in which ion
concentration is increased during electrodialysis.
[0085] The terms "conditioning conduit flow path" and "conditioning
flow path" refer to a fluid pathway, circuit or flow loop that
incorporates a source of a conditioning material, for example a
sodium salt or bicarbonate.
[0086] The term "conditioning flow path inlet" refers to a location
on a conditioning flow path where fluid enters the conditioning
flow path
[0087] The term "conditioning flow path outlet" refers to a
location on a conditioning flow path where fluid exits the
conditioning flow path.
[0088] The terms "conductivity meter," "conductivity sensor,"
"conductivity detector," conductivity electrode or the like, refer,
in context, to a device for measuring the electrical conductance of
a solution and/or the ion, such as a sodium ion, concentration of a
solution. In specific examples, the conductivity sensor, meter, or
conductor can be directed to a specific ion such as sodium and be
referred to as a "sodium electrode," "sodium sensor," "sodium
detector," or "sodium meter."
[0089] The term "conductive species" refers to a material's ability
to conduct an electric current. Electrolytes are an example of a
conductive species in dialysate fluids, such as, but not limited to
the presence sodium, potassium, magnesium, phosphate, and chloride
ions. A fluid's ability to conduct an electrical current is due in
large part to the ions present in the solution. A fluid's ability
to conduct an electrical current is due in large part to the ions
present in the solution.
[0090] The terms "conduit," "circuit," and "flow path" refer to a
vessel or passageway having a void volume through which a fluid can
travel or move. A conduit can have a dimension parallel to the
direction of travel of the fluid that is significantly longer than
a dimension orthogonal to the direction of travel of the fluid.
[0091] The term "connectable" refers to being able to be joined
together for purposes including but not limited to maintaining a
position, allowing a flow of fluid, performing a measurement,
transmitting power, and transmitting electrical signals. The term
"connectable" can refer to being able to be joined together
temporarily or permanently.
[0092] The term "consisting of" includes and is limited to whatever
follows the phrase "consisting of." Thus, the phrase indicates that
the limited elements are required or mandatory and that no other
elements may be present.
[0093] The term "consisting essentially of" includes whatever
follows the term "consisting essentially of" and additional
elements, structures, acts or features that do not affect the basic
operation of the apparatus, structure or method described.
[0094] The term "consumables" refers to components that are
dissipated, wasted, spent or used up during the performance of any
function in the present invention. Examples include a quantity of
sodium, bicarbonate, electrolytes, infusates, sorbents, cleaning
and disinfecting ingredients, anticoagulants, and components for
one or more concentrate solutions.
[0095] The terms "consumables cartridge" and "consumables
container" refer to an object or apparatus having or holding one or
more materials that are depleted during operation of the system.
The one or more materials may be in solid and/or solution form and
can be in separate compartments of the object or apparatus. The
object or apparatus may be single use, or may be replenished and
used multiple times, for example, by refilling the object to
replace the consumed material.
[0096] The terms "contact," "contacted," and "contacting" refers,
in context, to (1) a coming together or touching of objects,
fluids, or surfaces; (2) the state or condition of touching or of
immediate proximity; (3) connection or interaction. For example, in
reference to a "dialysate contacting a sorbent material" refers to
dialysate that has come together, has touched, or is in immediate
proximity to connect or interact with any material or material
layer of a sorbent container, system or cartridge.
[0097] The term "container" as used herein is a receptacle that may
be flexible or inflexible for holding fluid or solid, such as for
example a spent dialysate fluid, or a sodium chloride or sodium
bicarbonate solution or solid, or the like.
[0098] The term "contaminant" refers to an undesirable or unwanted
substance or organism that may cause impairment of the health of a
subject receiving a treatment or of the operation of the
system.
[0099] The term "control pump," such as for example an
"ultrafiltrate pump," refers to a pump that is operable to pump
fluid bi-directionally to actively control the transfer of fluid
volume into or out of a compartment or circuit.
[0100] The terms "control reservoir," "ultrafiltrate reservoir,"
"solution reservoir," "therapy solution reservoir," and "waste
reservoir," as the case may be, refers, in context, to a vessel or
container, optionally accessible by a control pump that contains a
variable amount of fluid, including fluid that can be referred to
as an ultrafiltrate. These reservoirs can function as a common
reservoir to store fluid volume from multiple sources in a system.
Other fluids that can be contained by these reservoirs include, for
example, water, priming fluids, waste fluids, dialysate, including
spent dialysate, and mixtures thereof. In certain embodiments, the
reservoirs can be substantially inflexible, or non-flexible. In
other embodiments, the reservoirs can be flexible containers such
as a polymer bag.
[0101] The term "control signals" refers to energy that is provided
from one element of a system to another element of a system to
convey information from one element to another or to cause an
action. For example, a control signal can energize a valve actuator
to cause a valve to open or close. In another example a switch on a
valve can convey the open or close state of a valve to a
controller.
[0102] A "control system" consists of combinations of components
that act together to maintain a system to a desired set of
performance specifications. The control system can use processors,
memory and computer components configured to interoperate to
maintain the desired performance specifications. It can also
include fluid control components, and solute control components as
known within the art to maintain the performance
specifications.
[0103] The terms "control valve" and "valve" refer to a device that
can be operated to regulate the flow of fluid through a conduit or
flow path by selectively permitting fluid flow, preventing fluid
flow, modifying the rate of fluid flow, or selectively guiding a
fluid flow to pass from one conduit or flow path to one or more
other conduits or flow paths.
[0104] The terms "controlled compliant flow path," "controlled
compliant dialysate flow path" and "controlled compliant solution
flow path" refer to flow paths operating within a controlled
compliant system having the characteristic of controlled
compliance, or of being controlled compliant as defined herein.
[0105] A "controller," "control unit," "processor," or
"microprocessor" is a device which monitors and affects the
operational conditions of a given system. The operational
conditions are typically referred to as output variables of the
system wherein the output variables can be affected by adjusting
certain input variables.
[0106] The terms "controlled compliance" and "controlled compliant"
describe the ability to actively control the transfer of fluid
volume into or out of a compartment, flow path or circuit. In
certain embodiments, the variable volume of fluid in a dialysate
circuit or controlled compliant flow path expands and contracts via
the control of one or more pumps in conjunction with one or more
reservoirs. The volume of fluid in the system is generally constant
(unless additional fluids are added to a reservoir from outside of
the system) once the system is in operation if the patient fluid
volume(s), flow paths, and reservoirs are considered part of the
total volume of the system (each individual volume may sometimes be
referred to as a fluid compartment). The attached reservoirs allow
the system to adjust the patient fluid volume by withdrawing fluid
and storing the desired amount in an attached control reservoir
and/or by providing purified and/or rebalanced fluids to the
patient and optionally removing waste products. The terms
"controlled compliance" and "controlled compliant" are not to be
confused with the term "noncompliant volume," which simply refers
to a vessel, conduit, container, flow path, conditioning flow path
or cartridge that resists the introduction of a volume of fluid
after air has been removed from a defined space such as a vessel,
conduit, container, flow path, conditioning flow path or cartridge.
In one embodiment, and as discussed herein and shown in the
drawings is that the controlled compliant system can move fluids
bi-directionally. In certain cases, the bi-directional fluid
movement is across a semi-permeable membrane either inside or
outside a dialyzer. The bi-directional fluid flow can also occur
across, through, or between vessels, conduits, containers, flow
paths, conditioning flow paths or cartridges of the invention in
selected modes of operation. The term "moving fluid
bi-directionally" as used in connection with a barrier, such as a
semi-permeable membrane, refers to the ability to move a fluid
across the barrier in either direction. "Moving fluid
bi-directionally" also can apply to the ability to move fluid in
both directions in the flow path or between a flow path and
reservoir in a controlled compliant system.
[0107] The terms "controlled compliant flow path," "controlled
compliant dialysate flow path" and "controlled compliant solution
flow path" refer to flow paths operating within a controlled
compliant system having the characteristic of controlled
compliance, or of being controlled compliant as defined herein.
[0108] The term "convective clearance" refers to the movement of
solute molecules or ions across a semi-permeable barrier due to
force created by solvent molecules moving across the semi-permeable
barrier.
[0109] The terms "controller," "control unit," "processor," and
"microprocessor" refers, in context, to a device which monitors and
affects the operational conditions of a given system. The
operational conditions are typically referred to as output
variables of the system wherein the output variables can be
affected by adjusting certain input variables.
[0110] The terms "coordinately operates" and "coordinately
operating" refer to controlling the function of two or more
elements or devices so that the combined functioning of the two or
more elements or devices accomplishes a desired result. The term
does not exclusively imply that all such elements or devices are
simultaneously energized.
[0111] The term "deaeration" refers to removing some or all of the
air contained in a liquid including both dissolved and
non-dissolved air contained in the liquid.
[0112] The terms "de-aeration flow path" and "de-aeration flow
path" refer to a set of elements that are configured in fluid
communication along a fluid flow pathway such that a liquid can be
passed through the fluid flow pathway to accomplish removal of some
or all of the air or gas contained in the liquid, including removal
of air or gas that is dissolved in the liquid.
[0113] The terms "degas module" and "degassing module" refer to a
component that separates and removes any portion of one or more
dissolved or undissolved gas from a liquid. A degas module can
include a hydrophobic membrane for allowing ingress or egress of
gases through a surface of the module while preventing the passage
of liquid through that surface of the module.
[0114] The term "deionization resin" refers to any type of resin or
material that can exchange one type of ion for another. In one
specific case, the term can refer to the removal of ions such as
potassium, magnesium, sodium and calcium in exchange for hydrogen
and/or hydroxide ions.
[0115] The term "detachable" refers to a characteristic of an
object or apparatus that permits it to be removed and/or
disconnected from another object or apparatus.
The term "dialysate" describes a fluid into or out of which solutes
from a fluid to be dialyzed diffuse through a membrane. A dialysate
typically contains electrolytes that are close in concentration to
the physiological concentration of electrolytes found in blood. A
common sodium level for dialysate is .about.140 mEq/L. Normal blood
sodium levels range from approximately 135 mEq/L to 145 mEq/L. The
REDY system typically uses dialysate ranging from 120 mEq/L to 160
mEq/L. In certain embodiment, a "predetermined limit" or
"predetermined concentration" of sodium values can be based off the
common sodium levels for dialysate and normal blood sodium levels.
"Normal" saline at 0/9% by weight and commonly used for priming
dialyzers and extracorporeal circuits is 154 mEq/L.
[0116] The terms "dialysate flow loop," "dialysate flow path," and
"dialysate conduit flow path" refers, in context, to a fluid
pathway that conveys a dialysate and is configured to form at least
part of a fluid circuit for hemodialysis, hemofiltration,
hemodiafiltration or ultrafiltration.
[0117] The terms "dialysate regeneration unit" and "dialysate
regeneration system" refer to a system for removing certain
electrolytes and waste species including urea from a dialysate
after contact with a dialyzer. In certain instances, the component
contained within the "dialysate regeneration unit" or "dialysate
regeneration system" can decrease the concentration or conductivity
of at least one ionic species, or release and/or absorb at least
one solute from a dialysate.
[0118] "Dialysis" is a type of filtration, or a process of
selective diffusion through a membrane. Dialysis removes solutes of
a specific range of molecular weights via diffusion through a
membrane from a fluid to be dialyzed into a dialysate. During
dialysis, a fluid to be dialyzed is passed over a filter membrane,
while dialysate is passed over the other side of that membrane.
Dissolved solutes are transported across the filter membrane by
diffusion between the fluids. The dialysate is used to remove
solutes from the fluid to be dialyzed. The dialysate can also
provide enrichment to the other fluid.
[0119] The terms "dialysis membrane," "hemodialysis membrane,"
"hemofiltration membrane," "hemodiafiltration membrane,"
"ultrafiltration membrane," and generally "membrane," refer, in
context, to a semi-permeable barrier selective to allow diffusion
and convection of solutes of a specific range of molecular weights
through the barrier that separates blood and dialysate, or blood
and filtrate, while allowing diffusive and/or convective transfer
between the blood on one side of the membrane and the dialysate or
filtrate circuit on the other side of the membrane.
[0120] The term "dialyzer" refers to a cartridge or container with
two flow paths separated by semi-permeable membranes. One flow path
is for blood and one flow path is for dialysate. The membranes can
be in the form of hollow fibers, flat sheets, or spiral wound or
other conventional forms known to those of skill in the art.
Membranes can be selected from the following materials of
polysulfone, polyethersulfone, poly(methyl methacrylate), modified
cellulose, or other materials known to those skilled in the
art.
[0121] "Diffusive permeability" is a property of a membrane
describing permeation by diffusion. Diffusion is the process of
solutes moving from an area of higher concentration to an area of
lower concentration.
[0122] The terms "diluate flow channel," "feed stream," "diluate
stream," and the like, refer, in context, to a fluid line of
solution entering an electrodialysis cell or electrodialysis unit
wherein the ion concentration in the fluid solution is changed.
[0123] The terms "diluent" and "diluate" refer to a fluid having a
concentration of a specific species less than a fluid to which the
diluent is added.
[0124] A "disc electrode" consists of an electrode with an
electrode head in the shape of a disc. A "rod electrode" refers to
an electrode in the shape of a rod or cylinder, with one end
functioning as an electrode head. A "sheet electrode" refers to an
electrode with an electrode head in the shape of a sheet. The sheet
can be square, rectangular, circular or other solid planar
geometries. A "mesh electrode" refers to an electrode with an
electrode head consisting of a mesh, where a mesh is the same as
that described for a mesh electrode. An "antenna electrode" refers
to an electrode with an electrode head in the shape of an antenna,
where antenna shape refers to a serpentine structure of conductive
wires or strips. A "pin electrode refers" to a rod electrode with a
small diameter. Other electrode and electrode head geometries can
be considered.
[0125] The term "disinfection fluid" refers to a solution for use
in cleaning and disinfecting an apparatus for hemodialysis,
hemodiafiltration or hemofiltration. The disinfection fluid may act
thermally, chemically, and combinations thereof to inhibit growth
of or to destroy microorganisms. The "disinfection fluid" may
further act to remove, at least in part, a buildup of
microorganisms on a surface of a fluid flow path, such buildups of
microorganisms may be commonly referred to as a biofilm.
[0126] The terms "diverted sample stream" and "diverting a sample
stream" refer redirecting part of a fluid from the main flow path
to accomplish another purpose, such as to measure a fluid
characteristic, remove a portion of the fluid stream in order to
take a sample. More than one sample stream may be diverted, such as
a "first sample stream, "second sample stream," "third sample
stream," "fourth sample stream," and the like.
[0127] The term "dry" as applied to a solid or a powder contained
in a cartridge means not visibly wet, and may refer interchangeably
to anhydrous and also to partially hydrated forms of those
materials, for example, monohydrates and dihydrates.
[0128] The term "downstream" refers to a direction in which a
moving dialysate or other fluid moves within a conduit or flow
path.
[0129] The term "downstream conductivity" refers to the
conductivity of a fluid solution as measured at a location of a
fluid flow path in the direction of the normal fluid flow from a
reference point.
[0130] The term "drain connection" refers to being joined in fluid
communication with a conduit or vessel that can accept fluid egress
from the system.
[0131] The term "dry composition" refers to a compound that does
not contain a substantial quantity of water and can include
anhydrous forms as well as hydrates for example, monohydrates and
dihydrates.
[0132] The term "effluent dialysate," as used herein describes the
discharge or outflow after the dialysate has been used for
dialysis.
[0133] The term "electrode" as used herein describes an electrical
conductor used to make contact with a nonmetallic part of a
circuit, such as electrical conductors used to contact the fluids
of the invention (e.g. dialysate) and to measure the conductivity
of the fluid.
[0134] The term "electrode" as used herein describes an electrical
conductor used to make contact with a part of a fluid, a solid or
solution. For example, electrical conductors can be used as
electrodes to contact any fluid (e.g. dialysate) to measure the
conductivity of the fluid or deliver or receive charge to the
fluid. A "disc electrode" consists of an electrode with an
electrode head in the shape of a disc. A "rod electrode" refers to
an electrode in the shape of a rod or cylinder, with one end
functioning as an electrode head. A "sheet electrode" refers to an
electrode with an electrode head in the shape of a sheet. The sheet
can be square, rectangular, circular or other solid planar
geometries. A "mesh electrode" refers to an electrode with an
electrode head consisting of a mesh, where a mesh is the same as
that described for a mesh electrode. An "antenna electrode" refers
to an electrode with an electrode head in the shape of an antenna,
where antenna shape refers to a serpentine structure of conductive
wires or strips. A "pin electrode" refers to a rod electrode with a
small diameter. Other electrode and electrode head geometries can
be considered.
[0135] The term "electrode array" refers to an array of one or more
electrodes contained in an insulator substrate. The insulator
substrate can be rigid or flexible and acts to isolate the
electrodes from each other. A non-limiting example of an "electrode
array" is a flex-circuit, which is a flexible circuit board
containing electrodes.
[0136] The term "electrode head" refers to the portion of an
electrode that is in physical contact with a fluid, that
conductivity is to be measured from.
[0137] The terms "electrode rinse" and "electrode rinse solution"
refer to any suitable solution such as sodium sulfate solution that
prevents undesirable oxidation and flushes reactants from an
electrode surface.
[0138] The terms "electrode rinse flow channel," "electrode rinse
stream," and the like refer to a fluid line of an electrode rinse
or "electrode rinse solution."
[0139] The term "electrode rinse reservoir" refers to a vessel or
container for holding the electrode rinse or electrode rinse
solution. The reservoir may have an inflexible or flexible volume
capacity.
[0140] The term "electrodialysis" refers to an electrically driven
membrane separation process capable of separating, purifying, and
concentrating desired ions from aqueous solutions or solvents.
[0141] The term "electrodialysis cell" refers to an apparatus
having alternating anion- and cation-exchange membranes that can
perform electrodialysis using an electrical driving force between
an anode and cathode housed at opposite ends of the cell. The cell
consists of a diluate compartment fed by a diluate stream and a
concentrate compartment fed by a concentrate stream. One or more
electrodialysis cells can be multiply arranged to form an
"electrodialysis stack."
[0142] The term "electrolyte" refers to an ion or ions dissolved in
an aqueous medium, including but not limited to sodium, potassium,
calcium, magnesium, acetate, bicarbonate, and chloride.
[0143] The terms "electrolyte source" and "electrolyte source"
refer to a stored substance that provides one or more
electrolytes.
[0144] The terms "equilibrated," "equilibrate," "to equilibrate,"
and the like, refer to a state where a concentration of a solute in
a first fluid has become approximately equal to the concentration
of that solute in the second fluid. However, the term equilibrated
as used herein does not imply that the concentration of the solute
in the first fluid and the second fluid have become equal. The term
can also be used in reference to the process of one or more gases
coming into equilibrium where the gases have equal pressures or
between a liquid and a gas.
[0145] The term "equilibrated to the solute species concentration"
refers to more specifically where a concentration of a particular
solute species in a first fluid has become approximately equal to
the concentration of that solute species in the second fluid. The
concentration need not be exact.
[0146] The terms "evacuation volume," "priming volume" and "void
volume" refer to the internal volume of a component or collection
of components comprising a fluid flow path and are the volume of
fluid that can be removed from the fluid flow path to empty the
fluid flow path if it has been filled with fluid.
[0147] The term "extracorporeal," as used herein generally means
situated or occurring outside the body.
[0148] The term "extracorporeal circuit" refers to a fluid pathway
incorporating one or more components such as, but not limited to,
conduits, valves, pumps, fluid connection ports or sensing devices
configured therein such that the pathway conveys blood from a
subject to an apparatus for hemodialysis, hemofiltration,
hemodiafiltration or ultrafiltration and back to the subject.
[0149] The terms "extracorporeal flow path pump" and "blood pump"
refer to a device to move or convey fluid through an extracorporeal
circuit. The pump may be of any type suitable for pumping blood,
including those known to persons of skill in the art, for example
peristaltic pumps, tubing pumps, diaphragm pumps, centrifugal
pumps, and shuttle pumps.
[0150] The term "feed solution" refers to a dialysate or
ultrafiltrate fluid solution introduced into part of the dialysis
or ultrafiltrate system. For example a "feed solution" can refer to
a dialysate or ultrafiltrate fluid solution introduced to an
electrodialysis cell.
[0151] The term "filtering media" refers to a material that can
allow a fluid to pass through, but which inhibits passage of
non-fluid substances that are larger than a predetermined size.
[0152] The terms "filtrate regeneration unit" and "filtrate
regeneration system" refer to a system for removing certain
electrolytes and waste species including urea from a filtrate
produced using filtration.
[0153] The terms "filtrate regeneration circuit," "filtrate
regeneration loop," and the like, refer to a flow path containing
fluid resulting from filtration; for the removal of certain
electrolytes and waste species including urea.
[0154] The term "filtration" refers to a process of separating
solutes from a fluid, by passing the fluid through a filter medium
across which certain solutes or suspensions cannot pass. Filtration
is driven by the pressure difference across the membrane.
[0155] The term "first terminal end" of a flow path refers to one
end of the flow path and "second terminal end" refers to another
end of the flow path. Neither the "first terminal end" nor the
"second terminal end" has any limitation on placement on an
arterial or venous side.
[0156] The term "first terminal valve" refers to a valve
substantially located at one end of a first fluid conduit without
any requirement that the valve be place on an arterial or venous
side. Similarly, the term "second terminal valve" refers to a valve
substantially located at one end of a second fluid conduit and so
on without any limitation on placement on an arterial or venous
side.
[0157] The term "flow loop" refers to a grouping of components that
may guide the movement of a fluid, convey the fluid, exchange
energy with the fluid, modify the composition of the fluid, measure
a characteristic of the fluid and/or detect the fluid. A flow loop
comprises a route or a collection of routes for a fluid to move
within. Within a flow loop there may be more than one route that a
volume of fluid can follow to move from one position to another
position. A fluid volume may move through a flow loop such that it
recirculates, or passes the same position more than once as it
moves through a flow loop. A flow loop may operate to cause fluid
volume ingress to and fluid volume egress from the flow loop. The
term "flow loop" and "flow path" often may be used interchangeably.
Further types of flow paths may be further defined; for example,
(1) a recirculation flow path, would be a flow path whose function
is in whole or part is to recirculate fluid through the defined
flow path; (2) a dialyzer recirculation flow path would be a flow
path whose function is in whole or part is to recirculate fluid
through the defined flow path having a dialyzer' (3) a controlled
compliant flow path would be a flow path would be a flow path that
is controlled compliant as defined herein. Any of the defined flow
paths may be referred to numerically, as a first flow path, second,
third flow path, or fourth flow path, and the like flow paths.
[0158] The term "flow path" refers to a route or a collection of
routes for a fluid to move within. Within a flow path there may be
more than one route that a fluid can follow to move from a first
position to a second position. A fluid may move through a flow path
such that it recirculates, or passes the same position more than
once as it moves through a flow path. A flow path may be a single
element such as a tube, or a flow path may be a grouping of
components of any type that guide the movement of a fluid. The term
"flow loop" and "flow path" often may be used interchangeably.
[0159] The terms "flow restriction," "flow restriction device" and
"flow restrictor" refer to an element or grouping of elements that
resist the flow of fluid through the element or grouping of
elements such that the fluid pressure within a flow stream that
passes through the element or grouping of elements is greater
upstream of the element or grouping of elements than downstream of
the element or grouping of elements. A flow restrictor may be an
active or passive device. Non-limiting examples of passive flow
restriction devices are orifices, venturis, a narrowing, or a
simple length of tubing with flow cross section that produces the
desired pressure drop when the fluid flows through it, such tubing
being essentially rigid or compliant. Non-limiting examples of
active flow restrictors are pinch valves, gate valves and variable
orifice valves.
[0160] The term "flow stream" refers to fluid moving along a flow
path
[0161] The term "fluid balance control pump" refers to where a
control pump is used to adjust the concentration or amount of a
solute or fluid in the system. For example, a fluid balance control
pump is used for selectively metering in or selectively metering
out a designated fluid wherein the concentration or amount of a
solute or fluid is adjusted.
[0162] The term "fluid characteristic" refers to any chemical or
biological components that make up or can be found dissolved or
suspended in the fluid or gas properties associated with the fluid;
or to any physical property of the fluid including, but not limited
to temperature, pressure, general or specific conductivities
associated with the fluid or related gases.
[0163] The term "fluid communication" refers to the ability of
fluid to move from one component or compartment to another within a
system or the state of being connected, such that fluid can move by
pressure differences from one portion that is connected to another
portion.
[0164] The term "flush reservoir" is used to describe a container
that can accept or store fluid that is removed from the system
during rinsing or cleaning of fluid pathways of the system,
including draining the system after cleaning and/or disinfection
has been completed.
[0165] "Hemodiafiltration" is a therapy that combines
hemofiltration and hemodialysis.
[0166] "Hemofiltration" is a therapy in which blood is filtered
across a semi-permeable membrane. Water and solutes are removed
from the blood via pressure-driven convection across the membrane.
The sieving properties of the membrane exclude certain solutes
above a certain threshold from crossing the membrane. One common
sieving property is "albumin sieving." In most situations it is not
desirable to remove albumin during renal replacement therapy, as
lower blood serum albumin is associated with increased mortality
rates. In hemofiltration, solutes small enough to pass through the
membrane in proportion to their plasma concentration are removed.
The driving force is a pressure gradient rather than a
concentration gradient. A positive hydrostatic pressure drives
water and solutes across the filter membrane from the blood
compartment to the filtrate compartment, from which it is drained.
Solutes, both small and large, get dragged through the membrane at
a similar rate by the flow of water that has been engineered by the
hydrostatic pressure. Hence, convection overcomes the reduced
removal rate of larger solutes (due to their slow speed of
diffusion) observed in hemodialysis. The rate of solute removal is
proportional to the amount of fluid removed from the blood circuit,
which can be adjusted to meet the needs of a clinical situation. In
general, the removal of large amounts of plasma water from the
patient requires volume substitution. Substitution fluid, typically
a buffered solution close to the plasma water composition a patient
needs, can be administered pre or post filter (pre-dilution mode,
post-dilution mode).
[0167] "Hemodialysis" is a technique where blood and a "cleansing
fluid" called dialysate are exposed to each other separated by a
semi-permeable membrane. Solutes within the permeability range of
the membrane pass while diffusing along existing concentration
gradients. Water and solutes are also transferred by convection
across a pressure gradient that may exist across the dialysis
membrane. The dialysate employed during hemodialysis has soluble
ions such as sodium, calcium and potassium ions and is not pure
water. The sieving properties of the membrane exclude certain
solutes above a certain threshold from crossing the membrane. One
common sieving property is "albumin sieving." In most situations it
is not desirable to remove albumin during renal replacement
therapy, as lower blood serum albumin is associated with increased
mortality rates.
[0168] The term "hemofilter" refers to a apparatus (or may refer to
a filter) used in hemofiltration. A hemofilter apparatus can be
connected to an extracorporeal circuit and configured to operate
with a semipermeable membrane that separates at least a portion of
the fluid volume from blood to produce a filtrate fluid.
[0169] The term "hydrophobic membrane" refers to a semipermeable
porous material that may allow gas phases of matter to pass
through, but which substantially resists the flow of water through
the material due to the surface interaction between the water and
the hydrophobic material.
[0170] "Hemodiafiltration" is a therapy that combines
hemofiltration and hemodialysis.
[0171] The term "in contact" as referred to herein denotes (a) a
coming together or touching, as of objects or surfaces; or (b) the
state or condition of touching or of being in immediate proximity.
"In contact" also includes fluids that are "in fluid communication
with" with a solid, such as for example, a fluid, like a dialysate,
in contact with a material layer of a sorbent cartridge, or a fluid
in contact with a sensor.
[0172] The terms "infusate container" and "infusate reservoir"
refer to a vessel, which can be substantially inflexible or
non-flexible for holding a solution of one or more salts for the
adjustment of the composition of a dialysate.
[0173] The term "infusate solution" refers to a solution of one or
more salts for the adjustment of the composition of a dialysate,
such as salts of calcium, magnesium, potassium, and glucose.
[0174] The term "infusate system" refers to a system that
incorporates at least one fluid pathway including components such
as conduits, valves, pumps or fluid connection ports, an infusate
container or a controller configured to add an infusate solution to
the dialysate.
[0175] The term "interchangeable bicarbonate cartridge" refers to a
bicarbonate cartridge that can be configured for removal and
replacement with a like bicarbonate cartridge. Interchangeable
bicarbonate cartridges can be single use disposable, or
re-fillable, re-usable containers.
[0176] The term "interchangeable sodium chloride cartridge" refers
to a sodium chloride cartridge that can be configured for removal
and replacement with a like sodium chloride cartridge.
Interchangeable sodium chloride cartridges can be single use
disposable, or re-fillable, re-usable containers.
[0177] The terms "introduce" and "introducing" refer to causing a
substance to become present where it was not present, or to cause
the amount or concentration of a substance to be increased.
[0178] The term "ion-exchange material" refers to any type of resin
or material that can exchange one type of ion for another. The
"ion-exchange material" can include anion and cation exchange
materials. In one specific case, the term can refer to the removal
of ions such as potassium, magnesium, sodium, phosphate and calcium
in exchange for other ions such as potassium, sodium, acetate,
hydrogen and/or hydroxide.
[0179] An "ion-exchange resin" or "ion-exchange polymer" is an
insoluble matrix (or support structure) that can be in the form of
small (1-2 mm diameter) beads, fabricated from an organic polymer
substrate. The material has a developed structure of pores on the
surface of which are sites with easily trapped and released ions.
The trapping of ions takes place only with simultaneous releasing
of other ions; thus the process is called ion-exchange. There are
multiple different types of ion-exchange resin which are fabricated
to selectively prefer one or several different types of ions. In
one specific case, the term can refer to the removal of ions such
as potassium, magnesium, sodium, phosphate and calcium in exchange
for other ions such as potassium, sodium, acetate, hydrogen and/or
hydroxide.
[0180] The term "ion selective electrode" (ISE), also known as a
specific ion electrode (SIE), is a transducer (or sensor) that
converts the activity of a specific ion dissolved in a solution
into an electrical potential, which can be measured by a voltmeter
or pH meter. The voltage is theoretically dependent on the
logarithm of the ionic activity, according to the Nernst equation.
The sensing part of the electrode is usually made as an
ion-specific membrane, along with a reference electrode.
[0181] The term "junction" refers to a common point of connection
between two or more flow paths or conduits that allows a liquid
and/or a gas to move from one pathway or conduit to another. A
junction may be a reversible connection that can be separated when
transfer of a liquid and/or gas between the flow paths or conduits
is not needed.
[0182] The term "kidney replacement therapy" as used herein
describes the use of a provided system to replace, supplement, or
augment the function of a patient with impaired kidney function,
such as would occur for a patient with Chronic Kidney Disease.
Examples of kidney replacement therapy would include dialysis,
hemofiltration, hemodialysis, hemodiafiltration, peritoneal
dialysis, and the like.
[0183] The terms "luer connector" and "luer adapter" refer to
adapters or connectors conforming to International Standards
Organization (ISO) standards 594-2.
[0184] The term "manifold" refers to a collection of one or more
fluid pathways that are formed within a single unit or subassembly.
Many types of manifolds can be used, e.g. a cleaning and/or
disinfecting manifold is used to clean or disinfect the defined
flow loop when the flow loop is connected to the cleaning and/or
disinfecting manifold.
[0185] The term "material layer" refers to the layers of materials
found in a sorbent cartridge. The material layers in a sorbent
cartridge may have one or more layers selected from a
urease-containing material, alumina, zirconium phosphate, zirconium
oxide, and activated carbon.
[0186] The term "memory" refers to a device for recording digital
information that can be accessed by a microprocessor, such as RAM,
Dynamic RAM, microprocessor cache, FLASH memory, or memory
card.
[0187] The term "mesh electrode" refers to an electrode in the
shape of a mesh, where a mesh consists of a planar structure with
openings. The mesh can be made from; overlapping wires or strips, a
sheet machined or manufactured to contain holes or openings, or a
sheet with a permeable, porous structure. In all cases the mesh is
manufactured from materials that result in electrodes, such as
titanium, platinum, stainless steel, and iridium. In the case of an
electrode mesh consisting of overlapping wires or strips, certain
wires or strips can be isolated from other wires or strips with an
insulator material in order to apply one polarity to certain wires
or strips and the opposite polarity to other wires or strips.
[0188] The term "metabolic waste species," as used herein describes
organic and inorganic components generated by a patient. They can
be metabolic products such as urea, uric acid, creatinine,
chlorides, inorganic sulfates and phosphate, or excess electrolytes
such as sodium, potassium, etc. It will be understood that the
specific "metabolic waste species" can vary between individuals
depending on diet and environmental factors. Hence, the term is
intended to encompass any waste component that is normally removed
by a kidney or by dialysis without restriction on the specific type
of waste substance.
[0189] The term "mid-weight uremic wastes" refers to uremic wastes
that can pass through a dialysis membrane and have a molecular
weight less than about 66,000 g/mol and greater than about 1000
g/mol. An example of a middle molecule is beta-2 microglobulin.
[0190] The term "mixing chamber" refers to a chamber or vessel,
with one or more inlet and outlet fluid streams, that provides
mixing between the fluid streams entering the chamber.
[0191] The term "moving fluid bi-directionally" as used in
connection with a barrier, such as a semi-permeable membrane,
refers to the ability to move a fluid across the barrier in either
direction. "Moving fluid bi-directionally" also can apply to the
ability to move fluid in both directions in the flow loop in a
controlled compliant system.
[0192] A multiplexer" or "mux" is an electronic device that selects
one of several analog or digital input signals and forwards the
selected input into a single line.
[0193] The term "nitrogenous waste" refers to any non-polymeric
nitrogen-containing organic compound originating from the blood of
a patient. Nitrogenous waste includes urea and creatinine, which
are both "waste species."
[0194] The term "one-way valve" refers to a device that allows flow
to pass in one direction through the valve, but prevents or
substantially resists flow through the valve in the opposite
direction. Such devices can include devices commonly referred to as
check valves
[0195] "Osmolarity" is defined as the number of osmoles of a solute
per liter of solution. Thus, a "hyperosmolar solution" represents a
solution with an increase in osmolarity compared to physiologic
solutions. Certain compounds, such as mannitol, may have an effect
on the osmotic properties of a solution as described herein.
[0196] The term "parallel or wound hollow fiber assembly" refers to
any device that incorporates a porous or non-porous hollow fiber
material that allows a gas to pass through the material wall of the
hollow fibers, but resists the passage of a liquid through the
material wall and is configured as multiple strands aligned in
parallel or wrapped around a core. The liquid to be degassed may be
conveyed through either the inside of the hollow fibers or around
the outside of the hollow fibers. Optionally, a gas may be conveyed
on the side of the material wall that is opposite the liquid to be
degassed. Optionally, a vacuum may be applied on the side of the
material wall that is opposite the liquid to be degassed.
[0197] A "patient" or "subject" is a member of any animal species,
preferably a mammalian species, optionally a human. The subject can
be an apparently healthy individual, an individual suffering from a
disease, or an individual being treated for a disease.
[0198] The term "parallel to a central axis" refers to the position
of components, e.g. sensors that can be placed in a plane having
portions generally parallel to the central axis.
[0199] The terms "pathway," "conveyance pathway" and "flow path"
refer to the route through which a fluid, such as dialysate or
blood travels.
[0200] The term "patient fluid balance" refers to the amount or
volume of fluid added to or removed from a subject undergoing a
treatment.
[0201] The term "peristaltic pump" refers to a pump that operates
by compression of a flexible conduit or tube through which the
fluid to be pumped passes.
[0202] The term "perpendicular to a central axis" refers to the
position of components, e.g. sensors that can be placed in a plane
having portions generally perpendicular to the central axis.
[0203] "Peritoneal dialysis" is a therapy wherein a dialysate is
infused into the peritoneal cavity, which serves as a natural
dialyzer. In general, waste components diffuse from a patient's
bloodstream across a peritoneal membrane into the dialysis solution
via a concentration gradient. In general, excess fluid in the form
of plasma water flows from a patient's bloodstream across a
peritoneal membrane into the dialysis solution via an osmotic
gradient.
[0204] The term "pH-buffer modifying solution" refers to a solution
that can reduce the acidity (pH) of the working dialysate solution
when added to the dialysate
[0205] The term "pH-buffer sensor" refers to a device for measuring
the acidity or basicity (pH) and the buffer concentration of the
dialysate solution.
[0206] The term "pH-buffer management system" refers to a system
managing the pH and buffer concentration of a dialysate by adding,
removing or generating a fluid to the dialysate such that the
dialysate is modified by the pH-buffer management system to have a
different pH and buffer concentration.
[0207] The term "pH-buffer measurement system" refers to a system
measuring the pH and/or buffer concentration of a dialysate or
fluid within the system.
[0208] The terms "portable system" and "wearable system" refers to
a system in whole or in part having a mass and dimension to allow
for transport by a single individual by carrying the system or
wearing the system on the individual's body. The terms are to be
interpreted broadly without any limitation as to size, weight,
length of time carried, comfort, ease of use, and specific use by
any person whether man, woman or child. The term is to be used in a
general sense wherein one of ordinary skill will understand that
portability as contemplated by the invention encompasses a wide
range of weights, geometries, configurations and size.
[0209] The term "potable water" refers to drinking water or water
that is generally safe for human consumption with low risk of
immediate or long term harm. The level of safety for human
consumption can depend on a particular geography where water safe
for human consumption may be different from water considered safe
in another jurisdiction. The term does not necessarily include
water that is completely free of impurities, contaminants,
pathogens or toxins. Other types of water suitable for use in the
present invention can include purified, deionized, distilled,
bottled drinking water, or other pre-processed water that would be
understood by those of ordinary skill in the art as being suitable
for use in dialysis.
[0210] The term "potassium-modified fluid" refers to fluid having a
different conductivity or potassium concentration compared to a
second fluid to which the potassium-modified fluid is added to
modify the conductivity or potassium concentration of the second
fluid.
[0211] The terms "physiologically compatible fluid" and
"physiological compatible solution" refer to a fluid that can be
safely introduced into the bloodstream of a living subject.
[0212] The term "plumbing," as used herein generally describes any
system of valves, conduits, channels, and lines for supplying any
of the fluids used in the invention.
[0213] The term "porosity," as used herein describes the fraction
of open pore volume of a membrane.
[0214] The terms "pressure differential" and "pressure drop" refer
to the difference in pressure measurements of a fluid between two
points of measurement.
[0215] The terms "pressure meter" and "pressure sensor" refer to a
device for measuring the pressure of a gas or liquid in a vessel or
container.
[0216] The terms "priming process" and "priming" refer to the
process of conveying a liquid into the void volume of a fluid
pathway to fill the pathway with liquid.
[0217] The term "priming volume" refers to the volume of priming
fluid required to fill the void volume of the subject pathway,
device, or component, as the particular case may be.
[0218] The term "priming overflow reservoir" refers to a reservoir
which during priming is used to collect the overflow of fluid
during the priming process.
[0219] The terms "processor," "computer processor," and
"microprocessor" as used herein are broad terms and are to be given
their ordinary and customary meaning to a person of ordinary skill
in the art. The terms refer without limitation to a computer
system, state machine, processor, or the like designed to perform
arithmetic or logic operations using logic circuitry that responds
to and processes the basic instructions that drive a computer. In
some embodiments, the terms can include ROM ("read-only memory")
and/or RAM ("random-access memory") associated therewith.
[0220] The term "programmable" as used herein refers to a device
using computer hardware architecture with a stored program and
being capable of carrying out a set of commands, automatically that
can be changed or replaced.
[0221] The term "pump" refers to any device that causes the
movement of fluids or gases by the application of suction or
pressure.
[0222] The term "pulsatile pump" refers to a pump where the pumped
fluid undergoes periodic variation in velocity and/or pressure.
[0223] The terms "reconstitute" and "reconstituting" refer to
creating a solution by addition of a liquid to a dry material or to
a solution of higher concentration to change the concentration
level of the solution. A "reconstitution system" in one use, is a
system that rebalances the dialysate in the system to ensure it
contains the appropriate amount of electrolytes and buffer.
[0224] The terms "sorbent regeneration," "sorbent regeneration
system," "sorbent system, and the like, refer, in context, to
devices that are part of a sorbent regenerated dialysate delivery
system for hemodialysis, functioning as an artificial kidney system
for the treatment of patients with renal failure or toxemic
conditions, and that consists of a sorbent cartridge and the means
to circulate dialysate through this cartridge and the dialysate
compartment of the dialyzer. The device is used with the
extracorporeal blood system and the dialyzer of the hemodialysis
system and accessories. The device may include the means to
maintain the temperature, conductivity, electrolyte balance, flow
rate and pressure of the dialysate, and alarms to indicate abnormal
dialysate conditions. The sorbent cartridge may include absorbent,
ion exchange and catalytiCs.
[0225] The term "shunt," as most often used herein describes a
passage between channels, in the described filtration and
purification systems, wherein the shunt diverts or permits flow
from one pathway or region to another. An alternate meaning of
"shunt" can refer to a pathway or passage by which a bodily fluid
(such as blood) is diverted from one channel, circulatory path, or
part to another. The term "bypass" can often be used
interchangeably with the term "shunt." [[0216]]
[0226] The term "sodium-concentrate solution" refers to a solution
having a high concentration of sodium ions relative to another
solution or fluid.
[0227] The terms "sodium chloride cartridge" and "sodium chloride
container" refer to an object that can be a stand-alone enclosure
or alternatively can be integrally formed with an apparatus for
hemodialysis, hemodiafiltration, or hemofiltration. The object can
store a source of sodium, such as sodium chloride in solid and/or
solution form, and can be configured to interface with at least one
other functional module found in systems for hemodialysis,
hemodiafiltration, or hemofiltration. For example, the sodium
chloride cartridge or container can contain at least one fluid
pathway and include components such as conduits, valves, filters or
fluid connection ports.
[0228] The term "regenerative capacity of the sorbent" refers to
the remaining capacity for the sorbent cartridge or a particular
material layer of the sorbent cartridge to perform its intended
function.
[0229] The term "regenerative substance" refers to a sorbent
material contained in a "regeneration module." The term "first
chosen regenerative substance," as used in the present invention
refers to a particular regenerative substance, identified as "first
chosen regenerative substance." The term "second chosen
regenerative substance" refers to a particular regenerative
substance, identified as "second chosen regenerative
substance."
[0230] The term "regeneration module" refers to an enclosure having
one or more sorbent materials for removing specific solutes from
solution, such as urea. In certain embodiments, the term
"regeneration module" includes configurations where at least some
of the materials contained in the module do not act by mechanisms
of adsorption or absorption.
[0231] The terms "remnant volume" and "residual volume" refer to
the volume of fluid remaining in a fluid flow path after the fluid
flow path has been partially emptied or evacuated.
[0232] The terms "replacement fluid" and "substitution fluid" refer
to fluid that is delivered to the blood of a subject undergoing
convective renal replacement therapies such as hemofiltration or
hemodiafiltration in order to replace at least a portion of the
fluid volume that is removed from the subject's blood when the
blood is passed through a hemofilter or a dialyzer.
[0233] The term "reserve for bolus infusion" refers to an amount of
solution available, if needed, for the purpose of administering
fluid to a subject receiving therapy, for example, to treat an
episode of intradialytic hypotension.
[0234] The term "reusable" refers to an item that is used more than
once. Reusable does not imply infinitely durable. A reusable item
may be replaced or discarded after one or more use.
[0235] The term "reverse osmosis" refers to a filtration method of
forcing a solvent from a region of high solute concentration
through a semipermeable membrane to a region of low solute
concentration by applying a pressure in excess of osmotic pressure.
To be "selective," this membrane should not allow large molecules
or ions through the pores (holes), but should allow smaller
components of the solution (such as the solvent) to pass
freely.
[0236] The term "reverse osmosis rejection fraction" refers to the
resulting solute that is retained on the pressurized side of the
membrane and the pure solvent is allowed to pass to the other side
in a reverse osmosis system.
[0237] The term "reversible connections" refers to any type of
detachable, permanent or non-permanent connection configured for
multiple uses.
[0238] The term "salination pump" refers to a pump configured to
move fluid and/or control movement of fluid through a conditioning
flow path, such as through or from a source of a conditioning
material such as sodium chloride or sodium bicarbonate.
[0239] The term "salination valve" refers to a valve configured to
control the flow of fluid in a conditioning flow path, such as
through or from a source of a conditioning material such as sodium
chloride or sodium bicarbonate.
[0240] The term "segment" refers to a portion of the whole, such as
a portion of a fluid flow path or a portion of a fluid circuit. A
segment is not limited to a tube or conduit, and includes any
grouping of elements that are described for a particular segment.
Use of the term "segment," by itself, does not imply reversible or
detachable connection to another segment. In any embodiment, a
segment may be permanently connected to one or more other segments
or removably or detachably connected to one or more segments.
[0241] The terms "selectively meter fluid in" and "selectively
meter fluid out" generally refer to a process for controllably
transferring fluids from one fluid compartment (e.g. a selected
patient fluid volume, flow path, or reservoir) to another fluid
compartment. One non-limiting example is where a control pump may
transfer a defined fluid volume container, reservoirs, flow paths,
conduit of the controlled compliant system. When fluid is moved
from a reservoir into another part of the system, the process is
referred to as "selectively metering fluid in" as related to that
part of the system. Similarly, one non-limiting example of removing
a defined volume of dialysate from a dialysate flow path in a
controlled compliant system and storing the spent dialysate in a
control reservoir, can be referred to as "selectively metering-out"
the fluid from the dialysate flow path.
[0242] The terms "semipermeable membrane," "selectively permeable
membrane," "partially permeable membrane," and "differentially
permeable membrane," refer to a membrane that will allow certain
molecules or ions to pass through it by diffusion and occasionally
specialized "facilitated diffusion". The rate of passage depends on
the pressure, concentration, and temperature of the molecules or
solutes on either side, as well as the permeability of the membrane
to each solute. The term "semi-permeable membrane" can also refer
to a material that inhibits the passage of larger molecular weight
components of a solution while allowing passage of other components
of a solution having a smaller molecular weight. For example,
Dialyzer membranes come with different pore sizes. Those with
smaller pore size are called "low-flux" and those with larger pore
sizes are called "high-flux." Some larger molecules, such as
beta-2-microglobulin, are not effectively removed with low-flux
dialyzers. Because beta-2-microglobulin is a large molecule, with a
molecular weight of about 11,600 daltons, it does not pass
effectively through low-flux dialysis membranes.
[0243] The term "sensor," which can also be referred to as a
"detector" in certain instances, as used herein can be a converter
that measures a physical quantity of a matter in a solution, liquid
or gas, and can convert it into a signal which can be read by an
electronic instrument.
[0244] The term "sensor element" refers to a device or component of
a system that detects or measures a physical property.
[0245] The terms "sodium management system" and "sodium management"
broadly refer to a system or process that can maintain the sodium
ion concentration of a fluid in a desired range. In certain
instances, the desired range can be within a
physiologically-compatible range. The sodium ion concentration of
an input solution can be modified by any means including
application of an electrical field.
[0246] The term "sodium-modified fluid" refers to fluid having a
different conductivity or sodium concentration compared to a second
fluid to which the sodium-modified fluid is added to modify the
conductivity or sodium concentration of the second fluid.
[0247] The term "sodium conduit flow path" refers to a flow path in
fluid communication with a sodium chloride cartridge which then can
pump saturated sodium solution into the dialysate by pumping and
metering action of a salination pump.
[0248] The term "sodium source" refers to a source from which
sodium can be obtained. For example, the sodium source can be a
solution containing sodium chloride or a dry sodium chloride
composition that is hydrated by the system.
[0249] The term "solid potassium" refers to a solid composition
containing a salt of potassium such as potassium chloride at any
purity level. In general, the solid potassium will be easily
soluble in water to form a solution.
[0250] The term "solid sodium" refers to a solid composition
containing a salt of sodium such as sodium chloride at any purity
level. In general, the solid potassium will be easily soluble in
water to form a solution and of high purity.
[0251] The term "solid bicarbonate" refers to a composition
containing a salt of bicarbonate such as sodium bicarbonate at any
purity level. In general, the solid bicarbonate will be easily
soluble in water to form a solution.
[0252] The term "solute" refers to a substance dissolved,
suspended, or present in another substance, usually the component
of a solution present in the lesser amount.
[0253] The terms "sorbent cartridge" and "sorbent container" refer
to a cartridge containing one or more sorbent materials for
removing specific solutes from solution, such as urea. "Sorbent
cartridge" includes configurations where at least some of the
materials contained in the cartridge do not act by mechanisms of
adsorption or absorption.
[0254] The terms "sorbent regeneration," "sorbent regeneration
system," "sorbent system, and the like, refer, in context, to
devices that are part of a sorbent regenerated dialysate delivery
system for hemodialysis, functioning as an artificial kidney system
for the treatment of patients with renal failure or toxemic
conditions, and that consists of a sorbent cartridge and the means
to circulate dialysate through this cartridge and the dialysate
compartment of the dialyzer. The device is used with the
extracorporeal blood system and the dialyzer of the hemodialysis
system and accessories. The device may include the means to
maintain the temperature, conductivity, electrolyte balance, flow
rate and pressure of the dialysate, and alarms to indicate abnormal
dialysate conditions. The sorbent cartridge may include absorbent,
ion exchange and catalytics.
[0255] The term "source of cations" refers a source from which
cations can be obtained. Examples of cations include, but are not
limited to, calcium, magnesium and potassium. The source can be a
solution containing cations or a dry composition that is hydrated
by the system. The cation infusate source is not limited to cations
and may optionally include other substances to be infused into a
dialysate or replacement fluid. Non-limiting examples include
glucose, dextrose, acetic acid and citric acid.
[0256] The term "specified gas membrane permeability" refers to a
determined rate at which a gas membrane will allow a gas to pass
through the membrane from a first surface to a second surface, the
rate being proportional to the difference in absolute pressure of
the gas in proximity to the first side of the membrane and in
proximity to the second side of the membrane.
[0257] The term "spent dialysate" refers to a dialysate that has
been contacted with blood through a dialysis membrane and contains
one or more impurity, or waste species, or waste substance, such as
urea.
[0258] The term "static mixer" refers to a device that mixes two or
more component materials in a fluid solution without requiring the
use of moving parts.
[0259] The term "substantially inflexible volume" refers to a
three-dimensional space within a vessel or container that can
accommodate a maximum amount of non-compressible fluid and resists
the addition of any volume of fluid above the maximum amount. The
presence of a volume of fluid less than the maximum amount will
fail to completely fill the vessel or container. Once a
substantially inflexible volume has been filled with a fluid,
removal of fluid from that volume will create a negative pressure
that resists fluid removal unless fluid is added and removed
simultaneously at substantially equal rates. Those skilled in the
art will recognize that a minimal amount of expansion or
contraction of the vessel or container can occur in a substantially
inflexible volume; however, the addition or subtraction of a
significant volume of fluid over a maximum or minimum will be
resisted.
[0260] The term "tap water" refers to water, as defined herein,
from a piped supply.
[0261] The term "temperature sensor" refers to a device that
detects or measures the degree or intensity of heat present in a
substance, object, or fluid.
[0262] A "therapy solution reservoir" refers to any container or
reservoir that holds a physiological compatible fluid.
[0263] The term "total bicarbonate buffer concentration" refers to
the total concentration of bicarbonate (HCO.sub.3.sup.-) ion and a
conjugate acid of bicarbonate in a solution or composition.
[0264] A "therapy solution reservoir" refers to any container or
reservoir that holds a physiological compatible fluid.
[0265] The terms "treating" and "treatment" refer to the management
and care of a patient having a pathology or condition by
administration of one or more therapy contemplated by the present
invention. Treating also includes administering one or more methods
of the present invention or using any of the systems, devices or
compositions of the present invention in the treatment of a
patient. As used herein, "treatment" or "therapy" refers to both
therapeutic treatment and prophylactic or preventative measures.
"Treating" or "treatment" does not require complete alleviation of
signs or symptoms, does not require a cure, and includes protocols
having only a marginal or incomplete effect on a patient.
[0266] The term "uremic wastes" refers to a milieu of substances
found in patients with end-stage renal disease, including urea,
creatinine, beta-2-microglobulin.
[0267] The term "ultrafiltrate" refers to fluid that is removed
from a subject by convection through a permeable membrane during
hemodialysis, hemofiltration, hemodiafiltration, or peritoneal
dialysis. The term "ultrafiltrate," as used herein, can also refer
to the fluid in a reservoir that collects fluid volume removed from
the patient, but such a reservoir may also include fluids or
collections of fluids that do not originate from the subject.
[0268] The term "ultrafiltration" refers to subjecting a fluid to
filtration, where the filtered material is very small; typically,
the fluid comprises colloidal, dissolved solutes or very fine solid
materials, and the filter is a microporous, nanoporous, or
semi-permeable medium. A typical medium is a membrane. During
ultrafiltration, a "filtrate" or "ultrafiltrate" that passes
through the filter medium is separated from a feed fluid. In
general, when transport across a membrane is predominantly
diffusive as a result of a concentration driving force, the process
is described herein as dialysis. When transport is primarily
convective as a result of bulk flow across the membrane induced by
a pressure driving force, the process is ultrafiltration or
hemofiltration depending on the need for substitution solution as
the membrane passes small solutes but rejects macromolecules. The
term "ultrafiltration" can also refer to the fluid removal from
blood during a dialysis or a hemofiltration process. That is,
ultrafiltration refers to the process of passing fluid through a
selective membrane, such as a dialysis or hemofiltration membrane,
in either a dialysis, a hemodiafiltration, or a filtration
process.
[0269] The terms "unbuffered sodium bicarbonate" or "solution of
unbuffered sodium bicarbonate" refer to a sodium bicarbonate
composition that is not buffered with a conjugate acid or base in
any amount, proportion or pH adjustment.
[0270] The term "upstream" refers to a direction opposite to the
direction of travel of a moving dialysate or other fluid within a
conduit or flow path.
[0271] The term "urea sensor" refers to a device for measuring or
allowing for the calculation of urea content of a solution. The
"urea sensor" can include devices measuring urease breakdown of
urea and measurement of the resulting ammonium concentration. The
sensing methods can be based on any one of conductimetric,
potentiometric, thermometric, magnetoinductic, optical methods,
combinations thereof and other methods known to those of skill in
the art.
[0272] The term "vacuum" refers to an action that results from
application of a pressure that is less than atmospheric pressure,
or negative to the reference fluid or gas.
[0273] The term "vent" as referred to in relationship to a gas,
refers to permitting the escape of a gas from an defined portion of
the system, such as, for example, as would be found in the
degassing module.
[0274] The term "void volume" refers to a specific volume that can
be occupied by a fluid in a defined space such as a dialysate
circuit of the invention including all components contained
therein.
[0275] The terms "waste species," "waste products" and "impurity
species" refers to any molecular or ionic species originating from
the patient or subject, including metabolic wastes, molecular or
ionic species including nitrogen or sulfur atoms, mid-weight uremic
wastes and nitrogenous waste. Waste species are kept within a
specific homeostasis range by individuals with a healthy renal
system.
[0276] The term "waste fluid" refers to any fluid that does not
have a present use in the operation of the system. Non-limiting
examples of waste fluids include ultrafiltrate, or fluid volume
that has been removed from a subject undergoing a treatment, and
fluids that are drained or flushed from a reservoir, conduit or
component of the system.
[0277] The term "working dialysate solution" refers to a dialysate
solution that is undergoing active circulation or movement through
a system including conduits, pathways, dialyzers and
cartridges.
Dialysis System
[0278] FIG. 1 is an example of a dialysis system consisting of a
blood path and a dialysate regeneration path separated by membranes
contained in a dialyzer 20. The blood enters the dialyzer 20
through a flow line inlet 22 and exits through a flow line outlet
24. The dialysate regeneration circuit shown in FIG. 1 consists of
a substantially inflexible volume flow loop 46. The dialysate
solution is recirculated with a dialysate pump 30 and allowed to
flow through a dialysate regeneration unit 32.
[0279] The dialysate regeneration unit 32 consists of components or
materials that are capable of removing solutes from the dialysate
including: urea, phosphate, calcium, magnesium, potassium,
creatinine, uric acid, beta-2-microglobulin and sulfate. The
dialysate regeneration unit 32 may also contain components or
materials that release or bind sodium during the process of
removing solutes from the dialysate. For example, the dialysate
regeneration unit 32 may consist of a sorbent cartridge containing
activated carbon, urease, zirconium phosphate and hydrous zirconium
oxide, similar to the sorbent cartridge used in the "REDY" system.
The dialysate regeneration unit is further capable of removing a
waste species from the dialysate and releasing a bicarbonate buffer
component, unbuffered sodium bicarbonate, carbon dioxide or
combinations thereof to the dialysate.
[0280] Blood circulating through the dialyzer 20 via an
extracorporeal circuit exchanges waste components with dialysate
circulating through the dialyzer 20 and dialysate flow loop 46.
Waste species including ions and uremic toxins, such as uric acid,
creatinine, and .beta.2-microglobin, and urea diffuse from the
blood to the dialysate within the dialyzer 20 via a semipermeable
membrane contained therein.
[0281] Regeneration of the dialysate within the dialysate flow loop
46 can be achieved through contacting the dialysate with sorbents
contained within the dialysate regeneration unit 32. Examples of
useful sorbent materials include the REDY sorbent system and U.S.
Pat. Nos. 3,669,880; 3,989,622; 4,581,141; 4,460,555; 4,650,587;
3,850,835; 6,627,164; 6,818,196; and 7,566,432 and U.S. Patent
Publications 2010/007838; 2010/0084330; and 2010/0078381 and
International Patent Publication WO 2009/157877 A1, which are
incorporated herein by reference. In some embodiments, the
dialysate regeneration unit 32 can contain one or more different
kinds of materials. Such materials can be one or more selected from
the following group: 1) a urease-containing material, where urease
is an enzyme that catalyzes the conversion of urea to ammonium ions
and carbon dioxide; 2) a zirconium phosphate (ZrP) material that
has the capacity to act as a cation exchanger by absorbing a large
quantity of ammonium ions in exchange for sodium and hydrogen ions;
3) a zirconium oxide material (ZrO), namely hydrous zirconium
oxide, which acts as an anion exchanger by exchanging phosphate for
acetate; and 4) an activated carbon material that has a surface
area for adsorption of wide range of impurities including metal
ions and uremic toxins, such as uric acid, creatinine, and
.beta.2-microglobin. In some embodiments, the zirconium phosphate
material can be replaced with a magnesium phosphate material.
[0282] The principal waste species removed during treatment of a
patient is urea that accumulates in the blood of individuals with
various degrees of kidney disease or impairment. Since urea is an
electrically neutral species, the dialysate regeneration unit 32
can convert urea to a charged ammonium species that can then be
removed from the dialysate before the dialysate exits the
regeneration unit 32. In certain embodiments, the ammonium may be
removed by an ion exchange material prior to exiting the dialysate
regeneration unit 32. However, in order to maintain electrical
neutrality, the removal of charged ammonium species is matched by
exchange with another charged species, which is sodium ion and/or
hydrogen ion in certain embodiments. Further, carbonate ion and/or
CO.sub.2 is also a product of urease activity. Dialysate typically
include a bicarbonate buffer; however, the generation of hydrogen
ions and carbonate ions by the dialysate regeneration unit 32 can
affect the pH and total bicarbonate buffer composition of the
dialysate.
[0283] In one embodiment, a urea sensor 41 measures the urea
concentration of the dialysate flowing to the dialysate
regeneration unit 32. However, it will be understood that the urea
sensor can be placed on any part of the dialysate loop and in one
or more locations using multiple sensors. The urea sensor can also
be integrally formed with one or more components of the system
including the dialysate regeneration unit 32. In certain aspects,
one or more urea sensors can function integrally with the sorbent
cartridge contained within the dialysate regeneration unit 32. A
flow sensor may be used, or a pump 30 that provides a known flow
rate, to determine, in combination with the urea sensor 41, the
amount of urea entering the dialysate regeneration unit 32. In
certain embodiments, the urea entering the dialysate regeneration
unit 32 will break down into ammonium carbonate. A portion of the
carbonate ions will convert to carbon dioxide or bicarbonate
depending on characteristics of the dialysate regeneration unit 32.
In certain embodiments the ammonium carbonate will pass through a
cation-exchange resin, such as zirconium phosphate, which will
remove ammonium in exchange for hydrogen ions and sodium ions. The
amount of hydrogen and sodium ions released will influence the
dialysate solution pH and ultimately the concentration of carbon
dioxide and bicarbonate in solution. It is possible to characterize
the system sufficiently to predict the resulting concentration of
carbon dioxide and bicarbonate that result for a given dialysate
concentration of urea entering the dialysate regeneration unit 32.
Knowing the concentration of bicarbonate resulting from urea allows
adjustment of the total buffer concentration in order to achieve a
specific therapeutic goal related to a patient's acid-base balance.
Methods to adjust the total buffer concentration are described
below.
[0284] Methods for measuring the urea concentration of the
dialysate with the urea sensor 41 include commercially available
sensors based on urease breakdown of urea and measurement of the
resulting ammonium concentration. Another method takes advantage of
certain embodiments of the dialysate regeneration unit 32. In one
embodiment, the dialysate regeneration unit 32 consists of multiple
sorbent layers, one of which is a urease layer. By measuring the
conductivity change of the dialysate solution before and after the
urease layer the concentration of urea in the dialysate can be
determined. As such, the term "urea sensor" refers to a combination
of elements and sensors that are individually or collectively used
to directly or indirectly indicate urea concentration. Indirect
indication of urea concentration can be determined by measuring
changes in conductivity, pH, CO.sub.2, or ammonia concentration
effected by urease breakdown of urea. The urea sensor can be
collocated with another system element, such as dialysate
regeneration unit 32. Other methods known to those skilled in the
art to measure urea in an aqueous solution may also be applied.
[0285] After passing through the dialysate regeneration unit 32,
the dialysate flows through a degasser 39. The degasser 39 acts to
remove gasses dissolved in solution and non-dissolved gasses from
the dialysate fluid, such as carbon dioxide, oxygen and nitrogen.
The degasser 39 can contain a chamber containing a hydrophobic
membrane allowing release of gas, also known as a membrane
contacting degasser. The hydrophobic membrane can contain
polytetrafluoroethylene (PTFE), polypropylene, or other suitable
materials that allow for gas removal, but retard water intrusion.
The degasser 39 may function passively or actively. Passive
degassing involves passing the dialysate through a degassing
chamber containing a hydrophobic membrane and allowing gas to
escape based on the uncontrolled environmental conditions on the
non-dialysate side of the membrane. Active degassing involves
passing the dialysate through a degassing chamber containing a
hydrophobic membrane and actively controlling the environmental
conditions on the non-dialysate side of the membrane. For example,
the non-dialysate side of the membrane can be placed under reduced
pressure to drive gas removal from the dialysate. The reduced
pressure could be controlled to influence the rate of gas removal.
Active degassing could also involve passing a stripping gas along
the non-dialysate side of the hydrophobic membrane. The stripping
gas can be the atmosphere contained on the exterior of the dialysis
system, or be supplied from a gas cylinder of nitrogen, argon,
helium, or other suitable gas. The flow rate of the stripping gas
can be controlled to influence the rate of gas removal. The rate of
gas removal could also be monitored with a flow meter in order to
perform closed-loop control of the active degasser. The degasser 39
can also include a chamber that promotes gas nucleation and
subsequent removal from the dialysate. For example, the degassing
chamber can have modified surfaces to increase surface area and
thereby promote gas removal. The degassing chamber can also contain
materials that have high-surface area, such as boiling stones or
surface modified particles. Gas nucleation promoters can be used
with both active and passive degassing methods. An example of
commercially available boiling stones is PTFE boiling stones sold
by Sigma-Aldrich (St. Louis, Mo.). An example of a commercially
available membrane contacting degasser is the Liqui-Cell
Minimodule.TM. sold by Membrana (Charlotte, N.C.).
[0286] After passing through the degasser 39 the dialysate flow
passes a conductivity sensor 40 and an optional pH-buffer sensor
45. In certain embodiments, a urea sensor is not required when a
pH-buffer sensor is used; however, the urea sensor can be used in
conjunction with the pH-buffer sensor for more accurate
measurements. The conductivity sensor 40 measures the conductivity
of the dialysate solution, which is a measure of the total sodium
concentration because sodium is the major conductive species in the
dialysate before and after the dialysate regeneration unit 32. The
conductivity sensor 40 can be used for safety purposes to determine
if the sodium concentration of the dialysate is at an acceptable
level for the patient. The pH-buffer sensor measures the pH and
buffer concentration of the dialysate solution. The pH sensor may
include various sensors known to those skilled in the art, such as
a standard pH electrode based sensor. Preferably the buffer sensor
is capable of measuring bicarbonate concentration. Measurement of
bicarbonate concentration is known to those skilled in the art and
can involve using the pH sensor and a carbon dioxide sensor. A
carbon dioxide sensor for measuring the partial pressure of carbon
dioxide could include a modified pH sensor containing a gas
permeable membrane mounted on a combination measuring/reference
electrode, also known as a Severinghaus electrode. Sensors to
measure the partial pressure of carbon dioxide in aqueous solution
are well known in the art. The partial pressure of a gas dissolved
in a liquid is the partial pressure of that gas which would be
generated in a gas phase in equilibrium with the liquid at the same
temperature. Once the pH and partial pressure of carbon dioxide are
known the bicarbonate concentration can be calculated using the
Henderson-Hasselbalch equation:
pH=pK.sub.a+log HCO.sub.3.sup.-/.alpha.(PCO.sub.2)
where .sub.PCO.sub.2 (partial pressure of carbon dioxide (mmHg) and
pH are measured. The pK.sub.a and .alpha. (solubility coefficient
of carbon dioxide in dialysate (mmol-liter.sup.-1-mmHg.sup.-1) will
be calculated for the dialysate solution at a given temperature.
The temperature may be measured with a temperature sensor along the
dialysate flow loop 46 or a temperature sensor may be integrated
into the pH measurement system. The pK.sub.a and .alpha. can be
calculated by methods known to those skilled in the art. The
bicarbonate concentration HCO.sub.3.sup.- can then be calculated.
In certain embodiments, the pH-buffer sensor 45 is optional. An
example of a commercially available pH sensor is the InPro3250i
sold by Mettler Toledo (Columbus, Ohio). An example of a
commercially available CO.sub.2 is the PCO.sub.2 Sensor sold by
Idronaut (Italy).
[0287] In one mode of operation, as shown in FIG. 1, after the
conductivity sensor 40 and pH-buffer sensor 45, the dialysate flow
passes a reconstitution system 43 having an infusate pump 42 and an
infusate reservoir 44. The reconstitution system 43 rebalances the
dialysate to ensure it contains the appropriate amount of
electrolytes and buffer. The infusate reservoir 44 can contain
multiple reservoirs each containing specific compounds. For
example, the infusate reservoir 44 can include a reservoir
containing a concentrated electrolyte solution such as calcium
acetate, magnesium acetate and potassium acetate. The infusate
reservoir 44 can also contain an additional reservoir having a
concentrated buffer solution such as sodium bicarbonate, or
alternatively, unbuffered sodium bicarbonate or any specified
desired acid or base equivalent. The acid or base equivalents are
desirably equivalents suitable for use in a dialysate and can be
selected by those of ordinary skill in the art. Multiple
reconstitution systems 43 can be used with the dialysis system
shown in FIG. 1.
[0288] Regenerated dialysate 25 passes through the dialyzer 20 and
exits as spent dialysate 23. The spent dialysate 23 flow passes an
ultrafiltration unit having an ultrafiltration or control pump 28
and a control reservoir 26. The control pump 28 removes fluid from
the dialysate loop 46 and because of the dialysate loop's 46
controlled compliant properties, a volume of fluid is drawn across
dialyzer 20 from the blood. The ultrafiltrate system acts to remove
ultrafiltrate from the patient and remove any fluid added in along
the dialysate loop 46, such as fluid from the reconstitution system
43. The fluid volume removed by control pump 28 is collected in the
control reservoir 26. In certain embodiments, the system of FIG. 1
can also be used with an open-volume dialysate loop similar to the
system shown in FIG. 3.
[0289] The system as shown in FIG. 1 can be operated through the
following steps. Spent dialysate passes the urea sensor 41 and the
concentration of urea in the dialysate is determined using methods
described above. Dialysate exits the dialysate regeneration unit 32
and flows through degasser 39, which removes un-dissolved carbon
dioxide from the dialysate. The dialysate continues to the
reconstitution system 43. In this embodiment, a pH-buffer sensor 45
is not included. The reconstitution system 43 adds electrolytes and
bicarbonate to the dialysate solution. The bicarbonate is contained
in its own reservoir as sodium bicarbonate of some known
concentration. The concentration of the bicarbonate solution
infused can range from dilute solution to a saturated solution
depending on volume limitations of the bicarbonate reservoir. The
bicarbonate solution is pumped into the dialysate circuit loop at a
variable rate depending on the dialysate urea concentration
measured with the urea sensor 41 and the resulting bicarbonate
concentration that results after flowing through the dialysate
regeneration unit 32. For example, in certain embodiments 15% of
the dialysate urea concentration will end up as bicarbonate.
However, the required dialysate bicarbonate concentration can vary
substantially. The rate of bicarbonate addition depends on the
patient's acid-base chemistry. In one non-limiting example, a
specific patient may require bicarbonate addition to the dialysate
of 1.5 mmol/minute. At a given time interval of therapy, if the
dialysate urea concentration is 20 mmol/liter, the resulting
bicarbonate concentration added to the dialysate by urea conversion
will equal 3 mmol/liter. If the dialysate is flowing at a rate of
400 ml/min, the addition of bicarbonate to the dialysate from urea
will be occurring at a rate of 1.2 mmol/minute. Therefore, the
bicarbonate from the reconstitution system 43 will only need to be
added at a rate of 0.3 mmol/minute. If the bicarbonate in the
reconstitution system 43 is at a concentration of 1000 mmol/liter,
the flow rate of bicarbonate will need to be 0.3 ml/minute for that
time interval. It will be understood the flow rates of bicarbonate
can be similarly varied as required by those of skill in the art to
achieve the desired bicarbonate concentration.
[0290] In certain embodiments, the components of the dialysate flow
loop 46 have a controlled compliant volume. As such, fluid is in
passive equilibrium from flowing from the extracorporeal circuit to
the dialysate flow loop 46 due to the controlled compliant volume
of the dialysate loop 46. The net balance of fluid is prevented
from passively flowing between the flow loop 46 to the
extracorporeal circuit via the dialyzer 20, since such a movement
of fluid will leave a vacuum in the flow loop 46 or require the
flow loop 46 to expand. Since the dialyzer can be a high-flux type
that readily allows for the passage of water, there is some fluid
flux back and forth across the dialyzer membrane due to the
pressure differential on the blood and dialysate sides of the
membrane. This is a localized phenomenon due to the low pressure
required to move fluid across the membrane and is called
backfiltration; however, this results in no net fluid gain or loss
by the patient, as described above.
[0291] As an additional advantage of the components forming the
dialysate flow loop 46 having a controlled compliant volume, the
dialysate flow loop 46 can further incorporate a control or
ultrafiltration pump 28 that can be operated bi-directionally to
cause the movement of fluid into and out of the dialysate flow loop
46. As described above, hemodialysis does not require a net
movement of fluid volume across the dialysate membrane. However, an
ultrafiltrate or control pump 28 can be employed to affect
ultrafiltration to provide a hemodiafiltration therapy to the
patient. Specifically, the action of typical pumps contemplated by
the invention function by expanding or contracting a space wherein
any suitable type of pump can be used in the present invention.
When the control or ultrafiltration pump 28 is provided on the
dialysis flow loop 46, the flow of fluid volume to and from the
dialysate flow loop 46 can be adjusted in a controlled fashion by
allowing for the movement of fluid across the dialysis membrane in
the dialyzer 20. The control or ultrafiltration pump 28 allows for
fluid to move from the dialysate flow loop 46 to the extracorporeal
circuit without creating a vacuum, wherein the operation of the
control pump 28 is controlled. Likewise, the control pump 28 allows
for fluid to move from the extracorporeal circuit, and hence the
patient's body via the action of the control pump 28 by actively
controlling flow to and from the dialysate flow loop 46. Movement
of fluid between the extracorporeal circuit and the dialysate flow
loop 46 can be accurately controlled and metered with removed fluid
or ultrafiltrate stored in control reservoir 26. In some
embodiments, the control reservoir 26 can be prefilled with water,
dialysate or other fluid for addition to the dialysate flow loop
46.
[0292] FIG. 2 is an example of a dialysis system similar to the
system shown in FIG. 1 except the system includes a pH-buffer
management system 38. Reference numbers between FIG.'s refer to the
same components unless noted otherwise. The dialysate exiting the
dialysate regeneration unit 32 flows through a pH management system
38 or a by-pass loop 36, regulated by a by-pass regulator 34. The
by-pass regulator 34 determines the amount of dialysate that passes
through the pH-buffer management system 38. The by-pass regulator
34 can be a pinch valve, on/off valve, or a valve with a range of
open conditions such as a needle valve. The pH-buffer management
system 38 acts to acidify the dialysate. The pH-buffer management
system 38 and by-pass loop 36 can be placed anywhere along flow
loop 46, but preferably immediately after the dialysate
regeneration unit 32. Because the dialysate regeneration unit 32
removes waste species from the dialysate, including urea and
certain electrolytes, the pH-buffer management system acts in
certain embodiments only on sodium-based salts. Specifically, the
removal of divalent ions in the dialysate regeneration unit, such
as calcium and magnesium, improves the performance of the pH-buffer
management system by minimizing precipitation of the divalent
salts. The use of a by-pass loop 36 is optional and may be removed
if the pH-buffer management system 38 actively controls the level
of acidification, which will be explained below.
[0293] After passing through the pH-buffer management system 38 and
by-pass loop 36 the dialysate flow passes the degasser 39 as
explained above. The pH-buffer management system serves to remove
positively charged species in favor of the addition of hydrogen
ions to maintain charge balance. The acidification of the dialysate
in the pH-buffer management system 38 acts to convert bicarbonate
in the fluid passing through the pH-buffer management system 38 to
carbon dioxide. The produced carbon dioxide can be removed with the
degasser 39. The degasser 39 can be used to remove un-dissolved
carbon dioxide and/or dissolved carbon dioxide to a certain level
in order to achieve a specific dialysate pH. The remaining
components and features shown in FIG. 2 work according to the
description given for FIG. 1 above.
[0294] FIG. 3 is an example of a dialysis system similar to that
shown in FIG. 2. However, the dialysate flow loop 46 shown in FIG.
3 includes a dialysate reservoir 48 rather than the controlled
compliant dialysate flow loop 46 described in FIG. 1. Dialysate
reservoir 48 is a variable volume reservoir. The dialysate
reservoir 48 can also be located between the dialysate regeneration
system 32 and the pH-buffer management system 38, or between the
pH-buffer management system 38 and the reconstitution system 43.
The dialysate fluid contained in dialysate reservoir 48 can vary
during the course of a hemodialysis run. Specifically, the volume
will increase as ultrafiltrate is removed from the patient by
filtration across dialyzer 20. The ultrafiltrate rate can be
controlled by adjusting the trans-membrane pressure across the
dialyzer with various valves on the blood lines and dialysate
lines, or balance chambers combined with a ultrafiltration pump, or
other means known to those skilled in the art.
[0295] FIGS. 4 and 5 show flow diagrams for a dialysis system with
a controlled compliant dialysate flow loop 46 and a pH-buffer
management system 38. The ultrafiltrate volume that is collected in
the control reservoir 26 is pumped through a pH-buffer management
system 38 with a pH-buffer management pump 50 and returned to the
dialysate flow loop 46 to act as a pH-buffer modifying solution.
The pH-buffer modifying solution is a solution generated by the
pH-buffer management system 38 that reduces the pH of the working
dialysate within the dialysate flow loop 46 when added thereto. As
shown in FIGS. 4 and 5, the pH-buffer management system 38
increases the acidity of the ultrafiltrate stored in the control
reservoir 26, which is then added to the dialysate flow loop 46 as
a pH-buffer modifying solution. FIG. 4 shows a flow diagram for
addition of the pH-buffer modified ultrafiltrate waste to the
dialysate flow loop 46 prior to or upstream from the dialysate
regeneration system 32. FIG. 5 shows a flow diagram for addition of
the pH-buffer modified ultrafiltrate waste to the dialysate flow
loop 46 after or downstream from the dialysate regeneration system
32. The pH-buffered-modified fluid generated from fluid in the
control reservoir 26 will contain waste species and electrolytes
including urea, creatinine, calcium, magnesium, and potassium. Some
of these species will be removed by the pH-buffer management system
38. It is expected that the concentration of waste species and
electrolytes will be low in the pH-buffered modified fluid.
Therefore, addition of the pH-buffered modified fluid after the
dialysate regeneration unit 32 should not have deleterious effects
on the dialysis therapy.
[0296] FIG. 6 shows a flow diagram for a dialysis system consisting
of a dialysate flow loop 46 that includes a variable volume
dialysate reservoir 48, similar to the flow path shown in FIG. 3.
The flow diagram also includes a pH-buffer management pump 38 that
draws fluid from the dialysate reservoir 48 and passes it through a
pH-buffer management system 38 that acts to acidify the draw
solution from dialysate reservoir 48. The solution that was drawn
from the dialysate reservoir 48 and modified in acidity is then
returned back to the dialysate flow loop 46. The measurements of
the pH and buffer concentration of the dialysate can be used by a
controller to determine the desired pH. Such measurements can also
be used to determine or control the rate at which an acidified
solution is infused into the dialysate. As shown in FIG. 6, the
solution is returned after or downstream from the dialysate
regeneration system 32, but fluid can also be returned before the
dialysate regeneration system 32. FIG. 7 shows a flow diagram for a
bipolar electrodialysis system that can function as a component of
the pH-buffer management system identified as 38 in any one of
FIGS. 1, 2, 3, 4, 5 and 6. The feed inlet 68 to the bipolar
electrodialysis system can be dialysate or ultrafiltrate waste. The
dialysate or ultrafiltrate enters the bipolar electrodialysis
system at the feed inlet 68 and passes through an electrodialysis
cell 54. The electrodialysis cell 54 has a stack of bipolar and
cation exchange membranes. At each end of the membrane stack is an
electrode 67 and 69 contained in an electrode compartment. The
electrode compartment is either continually, or non-continuously,
rinsed during operation with an electrode rinse solution contained
in the electrode rinse reservoir 58 and recirculated with the
electrode rinse pump 66. The electrode rinse solution can contain a
sodium sulfate solution, or any other suitable electrode rinse
solution. The use of sodium sulfate is preferred because oxidation
of sulfate does not occur to an appreciable amount under typical
operating conditions. The use of sodium chloride in the electrode
rinse must be avoided to prevent the oxidation of chloride to
chlorine at the electrodes, which may diffuse into the dialysate
stream and contaminate the dialysate. The electrode rinse acts to
continually flush reactants that may form at the electrode
surfaces. For example, the electrolysis of water will occur to some
extent at the electrodes resulting in the formation of hydrogen and
oxygen. In some cases, it will be desirable to include a degassing
module in the electrode rinse circuit to remove some of the formed
gases. The degassing module can have a hydrophobic membrane vent.
The stack of bipolar and cation exchange membranes results in
alternating flow channels through the electrodialysis cell 54. The
dialysate or ultrafiltrate passes through certain flow channels
that are acidified during operation. The solution referred to as
base concentrate is contained in the base concentrate reservoir 56
and recirculated through the electrodialysis cell 54 with the base
concentrate pump 64. The base concentrate solution may initially be
water, or any other suitable solution.
[0297] Between therapy sessions the electrodialysis cell can be
cleaned by reversing the polarity of the electrodes and flushing a
cleaning solution through the cell. The cleaning solution could
consist of water, saline, or a dilute acid. The dilute acid can
include citric or acetic acid, or other suitable acids. Reversing
the polarity of the electrodes will promote movement of ions from
the base concentrate circuit to the dilute acid circuit that can be
flushed from the cell. This cleaning method will extend the life of
the membranes.
[0298] A more detailed flow diagram of the electrodialysis cell 54
is shown in FIG. 8. Feed solution 68, dialysate or ultrafiltrate,
enters the electrodialysis cell 54 between the cation exchange side
of a bipolar membrane 74 and an individual cation exchange membrane
76. The bipolar membrane 74 has an anion exchange membrane and a
cation exchange membrane bonded together. Examples of bipolar
membranes and cation exchange membranes that could be used include
Neosepta BP-1E bipolar membrane and Neosepta CMX cation exchange
membrane produced by ASTOM Corporation. The cation exchange
membrane is designed to only allow cations to pass through it. The
bipolar membrane is designed to not allow cations and anions to
pass through it.
[0299] When a bipolar membrane is placed in an electrodialysis cell
as shown in FIG. 8, an applied voltage across the electrodes 69 and
67 will result in transport of anions and cations towards the anode
69 and cathode 67, respectively. Because anions or cations cannot
flow through the bipolar membranes 74, water contained in the
bipolar membranes 74 is split resulting in hydrogen and hydroxyl
ions. The hydroxyl anions flow out of the anion exchange membrane
towards the anode 69 and cations flow out of the cation exchange
membrane towards the cathode 67 as depicted in FIG. 8. Cations (M+)
entering the electrodialysis cell 54 through the feed inlet 68
migrate through the cation exchange membrane 76 if an electric
potential, of polarity shown, is applied across the electrodes 67
and 69. The cations (M+) combine with hydroxyl anions to form a
base stream 72 that is recirculated in the electrodialysis system
shown in FIG. 7. In some embodiments, the cations in the feed
coming from the dialysate solution includes primarily sodium ions
as cations because the other cations typically found in dialysate,
such as calcium, magnesium, and potassium, are removed by the
dialysate regeneration system 32. Where ultrafiltrate stored in
control reservoir 26 is used as feed solution to the pH-buffer
management system, the cations in the feed coming from control
reservoir 26 include sodium, calcium, magnesium and potassium. The
hydrogen cations generated in the bipolar membranes combine with
the anions (X-) from the feed solution 68 resulting in an acid
solution 70 exiting the electrodialysis cell 54 as shown in FIG. 8.
The anions in the feed solution 68 can include chloride,
bicarbonate, and acetate, or other anions found in the dialysate or
ultrafiltrate waste solutions. As shown in FIG. 8, the electrode
reactions that occur at the cathode 67 and anode 69, result in
hydrogen and oxygen gas generation. The potential applied across
the electrodes will influence the rate of acid formation. A higher
potential will result in more acid formation. The applied potential
can be varied to achieve a specific acidification of the dialysate
or ultrafiltrate solution. The bipolar electrodialysis cell 54
shown in FIG. 8 illustrates a single cell stack. In practice
multiple cell stacks could be contained in the cell 54 between the
electrodes 67 and 69. The unit cell is illustrated by the dashed
line 101. Multiple unit cells 101 can be stacked together to
increase the surface area of the membranes and increase the rate of
acid formation for a given potential across the electrodes 67 and
69. The precise number of stacked unit cells will vary depending on
the required surface area and can be determined by those of skill
in the art.
[0300] The acidified solution 70 exiting the electrodialysis system
converts a certain amount of bicarbonate in the dialysate contained
in the dialysate flow loop 46 to carbon dioxide, which results in a
decrease of the bicarbonate ion concentration in the dialysate due
to a shift in equilibrium caused by the addition of acid.
Non-dissolved carbon dioxide can be removed with the degasser 39
shown in the various FIGS.
[0301] FIG. 9A shows a pH-buffer management system 38 consisting of
two bipolar electrodialysis cells placed in series. The first
bipolar electrodialysis cell 54 consists of the same components and
functions the same as the bipolar electrodialysis cell 54 shown in
FIG. 7. The second bipolar electrodialysis cell 55 is similar to
the first cell 54 except the feed stream 70 passes through a flow
path in the cell that is depleted of anions in exchange for
hydroxyl ions, resulting in an increase of the solution pH.
Therefore, when a potential is applied across the anode 69 and
cathode 67 of the second bipolar electrodialysis cell 55 a basic
stream 71 exits the cell. Acid will be generated in an acid
concentrate flow loop 73 and be recirculated by an acid concentrate
pump 69. In operation bicarbonate ions will move into the acid
concentrate flow loop 73 and convert to carbon dioxide. Therefore,
it may be necessary to include a degassing module in the acid
concentrate flow loop 73 of the types described above in order to
remove accumulated carbon dioxide.
[0302] The feed solution 68 shown in FIG. 9A could consist of
dialysate or ultrafiltrate waste. Upon entering the bipolar
electrodialysis cells a potential can be applied across the
electrodes of the first cell 54 or the second cell 55 depending on
the need to increase or decrease the pH of the feed solution 68.
The bipolar electrodialysis cells 54 and 55 shown in FIG. 9A can
also be arranged in parallel, which requires a flow regulator at
the inlet to each cell to direct the dialysate or ultrafiltrate
waste flow through either the acidifying cell 54 or the basic cell
55.
[0303] FIG. 9B shows a pH-buffer management system 38 similar to
the system shown in FIG. 9A. However, the concentrate flow loop
72B, concentrate reservoir 56B and concentrate recirculating pump
64B are shared between the two bipolar electrodialysis cells 54 and
55. Therefore, during acidification of the feed stream 68 in the
first electrodialysis cell 54 a base concentrate will be generated
in the concentrate flow loop 72B. Also, while the pH is being
raised in the feed stream 70 to the second electrodialysis cell 55,
an acid concentrate will be generated in the concentrate flow loop
72B. The acid and base concentrates generated will neutralize each
other to some extent and will keep the pH closer to 7. In certain
embodiments the electrode rinse flow loops 60, electrode rinse
reservoir 58 and electrode rinse recirculating pump 66 may also be
combined into a single unit and shared between both electrodialysis
cells.
[0304] FIG. 10 is a more detailed flow diagram of the second
bipolar electrodialysis cell 55 shown in FIG. 9A and FIG. 9B. The
feed solution 70 enters the bipolar electrodialysis cell 55 between
the cation exchange side of a bipolar membrane 74 and an individual
anion exchange membrane 77. The bipolar membrane 74 consists of an
anion exchange membrane and a cation exchange membrane bonded
together. Examples of bipolar membranes and anion exchange
membranes that could be used include Neosepta BP-1E bipolar
membrane and Neosepta AMX anion exchange membrane produced by ASTOM
Corporation. The anion exchange membrane is designed to only allow
anions to pass through it. The bipolar membrane is designed to not
allow cations and anions to pass through it. When a bipolar
membrane is placed in the bipolar electrodialysis cell 55 as shown
in FIG. 9A, an applied voltage across the electrodes 69 and 67 will
result in transport of anions and cations towards the anode 69 and
cathode 67 respectively. Because anions or cations cannot flow
through the bipolar membranes 74 water contained in the bipolar
membranes 74 is split resulting in hydrogen and hydroxyl ions. The
hydroxyl anions flow out of the anion exchange membrane towards the
anode 69 and anions flow out of the anion exchange membrane towards
the anode 67 as depicted in FIG. 10. Anions (X-) entering the
second electrodialysis cell 55 through the feed inlet 70 migrate
through the anion exchange membrane 77 if an electric potential, of
polarity shown, is applied across the electrodes 67 and 69. The
anions (X-) combine with hydrogen ions to form an acid stream 73
that is recirculated in the second electrodialysis system shown in
FIG. 9A. The cations in the feed coming from the dialysate solution
include sodium because the other cations typically found in
dialysate such as calcium, magnesium, and potassium are removed by
the dialysate regeneration system 32. The cations in the feed
coming from the ultrafiltrate waste include sodium, calcium,
magnesium and potassium. The hydroxyl anions generated in the
bipolar membranes combine with the cations (M+) from the feed
solution 70 resulting in a basic solution 71 exiting the
electrodialysis cell 55 as shown in FIG. 10. The anions in the feed
solution 68 could include chloride, bicarbonate, and acetate, or
other anions found in the dialysate or ultrafiltrate waste
solutions. Also, shown in FIG. 10 are the electrode reactions that
occur at the cathode 67 and anode 69, which result in hydrogen and
oxygen gas. The potential applied across the electrodes will
influence the rate of base formation. A higher potential will
result in more base formation. The applied potential can be varied
to achieve a specific increase in pH of the dialysate or
ultrafiltrate solution. The bipolar electrodialysis cell 55 shown
in FIG. 10 illustrates a single cell stack. In practice multiple
cell stacks could be contained in the cell 55 between the
electrodes 67 and 69. The unit cell is illustrated by the dashed
line 102. Multiple unit cells 102 can be stacked together by those
of ordinary skill in the art to increase the surface area of the
membranes and increase the rate of base formation for a given
potential across the electrodes 67 and 69.
[0305] The basic solution 71 exiting the electrodialysis system
converts a certain amount of carbon dioxide in the dialysate to
bicarbonate, resulting in an increase of the bicarbonate
concentration in the dialysate. In situations where the
ultrafiltrate waste is being passed through the bipolar
electrodialysis cell 55 to increase the pH of the solution, care
must be taken to avoid precipitation of the calcium and magnesium,
by controlling the level of base generation in the cell. In certain
embodiments, it can be preferred to use the configuration shown in
FIG. 9A and FIG. 10 on the dialysate after the dialysate
regeneration unit 32 because the dialysate solution will be free of
calcium and magnesium salts.
[0306] FIG. 11 shows a flow diagram for pH-buffer management system
consisting of a three compartment bipolar electrodialysis cell 94.
Dialysate or ultrafiltrate waste feed solution 68 enters the
bipolar electrodialysis cell 94 and generates an acidic solution 92
and a basic solution 82. The acidic solution 92 is recirculated in
an acid flow loop and reservoir 88 and the basic solution 82 is
recirculated in a base flow loop and reservoir 80. Acid
recirculation occurs with pump 90 and base recirculation occurs
with pump 86. The electrode rinse solution reservoir 58 and
electrode rinse flow loop 60 function as previously described in
FIGS. 7 and 9. The acid flow loop 92 includes flow regulators 97
and 99 that allow a portion of the dialysate or ultrafiltrate waste
feed solution 68 to be diverted into and out of the acid flow loop
92 thereby acidifying the dialysate or ultrafiltrate waste.
Likewise, the base flow loop 82 includes flow regulators 96 and 98
that allow a portion of the dialysate or ultrafiltrate waste feed
solution 68 to be diverted into and out of the base flow loop 82
thereby increasing the pH of the dialysate or ultrafiltrate waste.
The flow regulators 96, 97, 98 and 99 can include 2-way valves. The
flow regulators 97 and 99 can be replaced with a single 3-way valve
and the flow regulators 96 and 98 can be replaced with a single
3-way valve. Other arrangements, known to those skilled in the art,
for the flow regulators can also be used. The flow regulators could
be of the type described for the by-pass flow loop illustrated in
FIGS. 2 and 3.
[0307] FIG. 12 is a detailed flow diagram of the three compartment
electrodialysis cell 94 shown in FIG. 11. The feed solution 68,
consisting of dialysate or ultrafiltrate waste, enters the cell
between a cation 76 and anion 77 exchange membranes. Anions (X-)
flow through the anion exchange membrane 77 towards the anode 69
and collect in the acid flow path 92. The bipolar membrane 74
contacting the acid flow path 92 produces hydrogen ions that
combine with the anions (X-) in the dialysate or ultrafiltrate
waste. The cations (M+) flow through the cation exchange membrane
76 towards the cathode 67 and collect in the base flow path 82.
Hydroxyl ions are created at the bipolar membrane 74 contacting the
base flow path 82 and combine with cations (M+) in the dialysate or
ultrafiltrate waste.
[0308] The bipolar electrodialysis cell 94 shown in FIG. 12
illustrates a single cell stack. In practice multiple cell stacks
could be contained in the cell 94 between the electrodes 67 and 69.
The unit cell is illustrated by the dashed line 103. Multiple unit
cells 103 can be stacked together to increase the surface area of
the membranes and increase the rate of base formation and acid
formation for a given potential across the electrodes 67 and
69.
[0309] The pH-buffer management system 38 in some embodiments can
be an acid feed solution instead of a bipolar electrodialysis
system. The acid feed solution could be contained in a reservoir
and delivered to the dialysate solution by a pump. Suitable acids
could include hydrochloric acid, phosphoric acid, acetic acid,
citric acid or other suitable acids.
[0310] In some embodiments the pH-buffer management system 38 can
be controlled using the pH-buffer sensor 45 shown in the various
figures and described above. For example, a particular patient may
require a constant dialysate bicarbonate concentration of the
dialysate entering 25 the dialyzer 20. After exiting the dialyzer
20 the spent dialysate 23 will contain an unknown level of
bicarbonate and urea. After passing through the dialysate
regeneration unit 32 the urea will contribute additional
bicarbonate. Measurement of the dialysate bicarbonate concentration
with sensor 45 will determine the level of acidification necessary
to remove excess bicarbonate from the dialysate, if necessary.
Also, if bicarbonate needs to be added to the dialysate the
reconstitution system 43 can be used.
[0311] FIG. 13 shows a flow diagram for a hemofiltration system
utilizing a dialysate regeneration unit 32 and a pH-buffer
management system 38. The blood in line 22 enters a hemofilter 101
and a portion is filtered across membranes contained in the
hemofilter 101. The hemofilter 101 can consist of a hollow-fiber
dialyzer, plate-and-frame dialyzer, or other suitable hemofilters.
The hemofilter 101 could contain high flux or low flux membranes
made from polysulfone, polyethersulfone, poly(methyl methacrylate),
cellulose, modified-cellulose or other suitable materials. The
filtration pump 105 determines the amount of filtrate coming across
the hemofilter. The filtrate 103 exiting the hemofilter 101 flows
passes an ultrafiltration pump 28 whereby ultrafiltrate is removed
from the filtrate and collected in an ultrafiltration reservoir 26.
The filtrate then passes through a dialysate regeneration unit 32,
pH-buffer management system 38, and infusate system 43 as described
above. The regenerated filtrate 109 then passes through a microbial
filter 111 before being directly infused into the blood as
replacement fluid. The microbial filter 111 could include an
ultrafilter filter, sterile filter, or other suitable microbial
filters. The microbial filter 111 could contain membranes made from
the same materials suitable for the hemofilter, preferably with
pore sizes 0.2 microns or smaller. The microbial filter 111 may
remove both viable organisms and endotoxin. The microbial filter
may be a single filter, or multiple filters, including redundant
filters. The hemofiltration system shown in FIG. 13 has a
fixed-volume filtrate flow loop 107. Hemofiltration has certain
benefits over hemodialysis including higher convective clearance
which increases the clearance rate of middle molecular weight
species like beta-2-microglobulin.
[0312] FIG. 14 shows a flow diagram for a hemodiafiltration system
utilizing a dialysate regeneration unit 32 and a pH-buffer
management system 38. The blood in line 22 enters a dialyzer 20 and
a portion is filtered across membranes contained in the dialyzer
20. The dialyzer 20 could consist of a hollow-fiber dialyzer,
plate-and-frame dialyzer, or other types of dialyzers. The dialyzer
20 could contain high flux or low flux membranes made from
polysulfone, polyethersulfone, poly(methyl methacrylate),
cellulose, modified-cellulose or other suitable materials. The
dialysate 23 exiting the dialyzer 20 flows passes an
ultrafiltration pump 28 whereby ultrafiltrate is removed from the
dialysate and collected in an ultrafiltration reservoir 26. The
dialysate is recirculated in the dialysate flow loop 46 with a
dialysate pump 30. The dialysate then passes through a dialysate
regeneration unit 32, pH-buffer management system 38, and infusate
system 43 as described above. A portion of the regenerated
dialysate 115 is removed from the dialysate flow loop 46 with the
replacement fluid pump 117 passed through a microbial filter 111
and then directly infused into the blood as replacement fluid. The
control pump 117 can prevent flow of regenerated dialysate back to
the patient when not desired by pressurizing a portion of the line
or by not operating or creating a block in the line. Alternatively,
a control valve (not shown) can be placed at a junction between the
control pump 117 and a dialysate return line to the dialyzer 20.
The control valve can be 2-way or 3-way as required by the
dialysate flow loop 46 and prevent flow to the patient. When flow
of the regenerated dialysate back to the patient is desired,
control pump 117 can pump and allow flow to the patient, or the
control valve can be operated to allow flow. The specific
arrangement of valves and pumps and types thereof to accomplish the
requirements of the invention are within the ordinary skill of
those in the art. The microbial filter 111 could include an
ultrafilter filter, sterile filter, or other suitable microbial
filters. The microbial filter 111 could contain membranes made from
the same materials suitable for the dialyzer, preferably with pore
sizes 0.2 microns or smaller. The microbial filter 111 may remove
both viable organisms and endotoxin. The microbial filter may be a
single filter, or multiple filters, including redundant filters.
The hemodiafiltration system shown in FIG. 14 has a fixed-volume
dialysate flow loop 46. Hemodiafiltration combines the benefits
achieved with hemodialysis and hemofiltration, including maximum
small molecule diffusive clearance and maximum middle molecule
convective clearance.
[0313] FIG. 15 shows a flow diagram for a peritoneal dialysis
system utilizing a dialysate regeneration unit 32 and a pH-buffer
management system 38. Initially, a patient's peritoneal cavity 121
is filled with a certain volume of dialysate. After a certain
period of time spent dialysate is drawn out of the peritoneal
cavity 121 through a catheter 123 with a reversible dialysate pump
125. The spent dialysate flows through a check valve 127 and is
prevented from flowing through flow line 133 because of a check
valve 135. The spent dialysate continues through the dialysate
regeneration unit 32 via flowpath 129 to pH-buffer management
system 38 and the infusate system 43. In the case of peritoneal
dialysis, the infusate system 43 will include infusate containing
high levels of glucose or icodextrin in certain embodiments. The
regenerated dialysate is collected in a dialysate reservoir 131.
After a desired amount of regenerated dialysate has been collected
in the dialysate reservoir 131 the dialysate pump 125 is reversed
and fluid is drawn out of the dialysate reservoir 131. The fluid
flows through a check valve 135 and is directed through the
catheter 123 back into the peritoneal cavity. Those skilled in the
art will recognize that other configurations of pumps and valves
can accomplish the same function, for example, valves 127 and 135
can be combined into a single 3-way valve, or pump 125 may be
non-reversible if valves 127 and 135 are 2-way valves and pump 125
is placed downstream from valve 127.
[0314] This process can be continued until the dialysate
regeneration system is exhausted or until the therapy is complete.
At the end of a therapy the patient will have collected a certain
volume of ultrafiltrate in their peritoneal cavity. The
ultrafiltrate can be removed using the ultrafiltration pump 28 and
collected in the ultrafiltration reservoir 26. Likewise, during the
therapy, while spent dialysate is being removed from the patient, a
portion of the spent dialysate can be removed as ultrafiltrate with
the ultrafiltrate pump 28. However, the amount of ultrafiltrate a
patient generates is variable and depends on several factors
including properties of their peritoneum, dialysate composition,
and patient fluid volume, or overload. Therefore, care must be
taken when operating the ultrafiltrate pump 28 during the therapy
in order to avoid depleting the dialysate contained in the
peritoneal cavity 121.
[0315] It will be apparent to one skilled in the art that various
combinations and/or modifications and variations can be made in the
dialysis system depending upon the specific needs for operation.
Moreover, features illustrated or described as being part of one
embodiment may be used on another embodiment to yield a still
further embodiment.
* * * * *