Note: Descriptions are shown in the official language in which they were submitted.
1
HEMODIALYSIS SYSTEM WITH VARIABLE DIALYSATE FLOW RATE
Technical Field
[001] The present invention relates to an artificial kidney system for use in
providing
dialysis. More particularly, the present invention is directed to a
hemodialysis system
directed to a hemodialysis system.
Background
[002] Hemodialysis is a medical procedure that is used to achieve the
extracorporeal
removal of waste products including creatine, urea, and free water from a
patient's blood
involving the diffusion of solutes across a semipermeable membrane. Failure to
properly
remove these waste products can result in renal failure.
[003] During hemodialysis, the patient's blood is removed by an arterial line,
treated by
a dialysis machine, and returned to the body by a venous line. The dialysis
machine
includes a dialyzer containing a large number of hollow fibers forming a
semipermeable
membrane through which the blood is transported. In addition, the dialysis
machine
utilizes a dialysate liquid, containing the proper amounts of electrolytes and
other
essential constituents (such as glucose), that is also pumped through the
dialyzer.
[004] Typically, dialysate is prepared by mixing water with appropriate
proportions of
an acid concentrate and a bicarbonate concentrate. Preferably, the acid and
the
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bicarbonate concentrate are separated until the final mixing right before use
in the
dialyzer as the calcium and magnesium in the acid concentrate will precipitate
out when
in contact with the high bicarbonate level in the bicarbonate concentrate. The
dialysate
may also include appropriate levels of sodium, potassium, chloride, and
glucose.
[005] The dialysis process across the membrane is achieved by a combination of
diffusion and convection. The diffusion entails the migration of molecules by
random
motion from regions of high concentration to regions of low concentration.
Meanwhile,
convection entails the movement of solute typically in response to a
difference in
hydrostatic pressure. The fibers forming the semipermeable membrane separate
the
blood plasma from the dialysate and provide a large surface area for diffusion
to take
place which allows waste, including urea, potassium and phosphate, to permeate
into the
dialysate while preventing the transfer of larger molecules such as blood
cells,
polypeptides, and certain proteins into the dialysate.
[006] Typically, the dialysate flows in the opposite direction to blood flow
in the
extracorporeal circuit. The countercurrent flow maintains the concentration
gradient
across the semipermeable membrane so as to increase the efficiency of the
dialysis. In
some instances, hemodialysis may provide for fluid removal, also referred to
as
ultrafiltration. Ultrafiltration is commonly accomplished by lowering the
hydrostatic
pressure of the dialysate compaiiment of a dialyzer, thus allowing water
containing
dissolved solutes, including electrolytes and other permeable substances, to
move across
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the membrane from the blood plasma to the dialysate. In rarer circumstances,
fluid in the
dialysate flow path portion of the dialyzer is higher than the blood flow
portion, causing
fluid to move from the dialysis flow path to the blood flow path. This is
commonly
referred to as reverse ultrafiltration. Since ultrafiltration and reverse
ultrafiltration can
increase the risks to a patient, ultrafiltration and reverse ultrafiltration
are typically
conducted while supervised by highly trained medical personnel.
[007] Unfortunately, hemodialysis suffers from numerous drawbacks. An
arteriovenous
fistula is the most commonly recognized access point. To create a fistula, a
doctor joins
an artery and a vein together. Since this process bypasses the patient's
capillaries, blood
flows rapidly. For each dialysis session, the fistula must be punctured with
large needles
to deliver blood into, and return blood from, the dialyzer. Typically, this
procedure is
done three times a week, for 3 ¨4 hours at an out-patient facility. To a
lesser extent,
patients conduct hemodialysis at home. Home dialysis is typically done for two
hours,
six days a week. However, home hemodialysis requires more frequent treatment.
[008] Home hemodialysis suffers from still additional disadvantages. Current
home
dialysis systems are big, complicated, intimidating, and difficult to operate.
The
equipment requires significant training. Home hemodialysis systems are
currently too
large to be portable, thereby preventing hemodialysis patients from traveling.
Home
hemodialysis systems are expensive and require a high initial monetary
investment,
particularly compared to in-center hemodialysis where patients are not
required to pay for
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the machinery. Present home hemodialysis systems do not adequately provide for
the
reuse of supplies, making home hemodialysis economically less feasible to
medical
suppliers. As a result of the above-mentioned disadvantages, very few
motivated patients
undertake the drudgery of home hemodialysis.
[009] Furthermore, hemodialysis systems utilizing sorbent filters have not
been widely
accepted. Unfortunately, the sorbent filters are relatively expensive and can
be spent
quickly due to ion exchange that occurs as excess dialyzed ions ¨ K+, Ca++,
Mg++ and
phosphate (PO4) are exchanged for benign or less toxic ions like Na+, H+,
bicarbonate
(HCO3-) and acetate.
[010] Accordingly, there is a significant need for a hemodialysis system that
is
transportable, lightweight, easy to use, patient-friendly and thus capable of
in-clinic or in-
home use.
[011] Moreover, it would be desirable to provide a hemodialysis system that
possessed
no single-point of failure in the pumps, motors, tubes, or electronics which
would
endanger a patient.
[012] In addition, it would be desirable to provide a hemodialysis system that
was
capable of being used in a variety of modes, such as with a filter to cleanse
dialysate or
without a filter.
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[013] In addition, it would be desirable to operate the hemodialysis system in
a manner
that maximized the life of the sorbent filter.
[014] Aspects of the present invention fulfill these needs and provide further
related
advantages as described in the following summary.
Summary
[015] According to a first aspect of the invention, a hemodialysis system is
provided
including an arterial blood line for connecting to a patient's artery for
collecting blood
from a patient, a venous blood line for connecting to a patient's vein for
returning blood
to a patient, a reusable dialysis machine and a disposable dialyzer.
[016] The arterial blood line and venous blood line may be typical
constructions known
to those skilled in the art. For example, the arterial blood line may be
traditional flexible
hollow tubing connected to a needle for collecting blood from a patient's
artery.
Similarly, the venous blood line may be a traditional flexible tube and needle
for
returning blood to a patient's vein. Various constructions and surgical
procedures may be
employed to gain access to a patient's blood including an intravenous
catheter, an
arteriovenous fistula, or a synthetic graft.
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[017] Preferably, the disposable dialyzer has a construction and design known
to those
skilled in the art including a blood flow path and a dialysate flow path. The
term "flow
path" is intended to refer to one or more fluid conduits, also referred to as
passageways,
for transporting fluids. The conduits may be constructed in any manner as can
be
.. determined by those skilled in the art, such as including flexible medical
tubing or non-
flexible hollow metal or plastic housings. The blood flow path transports
blood in a
closed loop system by connecting to the arterial blood line and venous blood
line for
transporting blood from a patient to the dialyzer and back to the patient.
Meanwhile, the
dialysate flow path transports dialysate in a closed loop system from a supply
of dialysate
to the dialyzer and back to the dialysate supply. Both the blood flow path and
the
dialysate flow path pass through the dialyzer, but the flow paths are
separated by the
dialyzer's semipermeable membrane.
[018] Preferably, the hemodialysis system contains a reservoir for storing a
dialysate
solution. The reservoir connects to the hemodialysis system's dialysate flow
path to form
a closed loop system for transporting dialysate from the reservoir to the
hemodialysis
system's dialyzer and back to the reservoir. Alternatively, the hemodialysis
system
possesses two (or more) dialysate reservoirs which can be alternatively placed
within the
dialysate flow path. When one reservoir possesses contaminated dialysate,
dialysis
treatment can continue using the other reservoir while the reservoir with
contaminated
dialysate is emptied and refilled. The reservoirs may be of any size as
required by
clinicians to perform an appropriate hemodialysis treatment. However, it is
preferred that
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the two reservoirs be the same size and sufficiently small so as to enable the
dialysis
machine to be easily portable. Acceptable reservoirs are 0.5 liters to 6.0
liters in size.
Where the hemodialysis system includes only one reservoir, an acceptable
reservoir has a
volume of 12.0 liters.
[019] The hemodialysis system preferably possesses one or more heaters
thermally
coupled to the reservoirs for heating dialysate stored within the reservoir.
In addition, the
hemodialysis system includes temperature sensors for measuring the temperature
of the
dialysate within the reservoirs. The hemodialysis system preferably possesses
a fluid
level sensor for detecting the level of fluid in the reservoir. The fluid
level sensor may be
any type of sensor for determining the amount of fluid within the reservoir.
Acceptable
level sensors include magnetic or mechanical float type sensors, conductive
sensors,
ultrasonic sensors, optical interfaces, and weight measuring sensors such as a
scale or
load cell for measuring the weight of the dialysate in the reservoir.
[020] Preferably, the dialysis includes three primary pumps. The first and
second
"dialysate" pumps are connected to the dialysate flow path for pumping
dialysate through
the dialysate flow path from a reservoir to the dialyzer and back to the
reservoir.
Preferably, a first pump is positioned in the dialysate flow path "upflow",
(meaning prior
in the flow path) from the dialyzer while the second pumps is positioned in
dialysate flow
path "downflow" (meaning subsequent in the flow path) from the dialyzer.
Meanwhile,
the hemodialysis system's third primary pump is connected to the blood flow
path. This
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"blood" pump pumps blood from a patient through the arterial blood line,
through the
dialyzer, and through the venous blood line for return to a patient. It is
preferred that the
third pump be positioned in the blood flow path, upflow from the dialyzer.
[021] The hemodialysis system may also contain one or more sorbent filters for
removing toxins which have permeated from the blood plasma through the
semipermeable membrane into the dialysate. Filter materials for use within the
filter are
well known to those skilled in the art. For example, suitable materials
include resin beds
including zirconium-based resins. Acceptable materials are also described in
U.S. Patent
No. 8,647,506 and U.S. Patent Publication No. 2014/0001112.
[022] In a first embodiment, the sorbent filter is connected to the dialysate
flow path
downflow from the dialyzer so as to remove toxins in the dialysate prior to
the dialysate
being transported back to a reservoir. In a second embodiment, the filter is
outside of the
closed loop dialysate flow path, but instead is positioned within a separate
closed loop
"filter" flow path that selectively connects to either one of the two
dialysate reservoirs.
For this embodiment, preferably the hemodialysis system includes an additional
fluid
pump for pumping contaminated dialysate through the filter flow path and its
filter.
[023] Preferably, the hemodialysis system includes two additional flow paths
in the
form of a "drain" flow path and a "fresh dialysate" flow path. The drain flow
path
includes one or more fluid drain lines for draining the reservoirs of
contaminated
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dialysate, and the fresh dialysate flow path includes one or more fluid fill
lines for
transporting fresh dialysate from a supply of fresh dialysate to the
reservoirs. One or
more fluid pumps may be connected to the drain flow path and/or a fresh
dialysate flow
path to transport the fluids to their intended destination.
[024] In addition, the hemodialysis system includes a plurality of fluid valve
assemblies
for controlling the flow of blood through the blood flow path, for controlling
the flow of
dialysate through the dialysate flow path, and for controlling the flow of
used dialysate
through the filter flow path. The valve assemblies may be of any type of
electro-
mechanical fluid valve construction as can be determined by one skilled in the
art
including, but not limited to, traditional electro-mechanical two-way fluid
valves and
three-way fluid valves. A two-way valve is any type of valve with two ports,
including
an inlet port and an outlet port, wherein the valve simply permits or
obstructs the flow of
fluid through a fluid pathway. Conversely, a three-way valve possesses three
ports and
functions to shut off fluid flow in one fluid pathway while opening fluid flow
in another
pathway. In addition, the dialysis machine's valve assemblies may include
safety pinch
valves, such as a pinch valve connected to the venous blood line for
selectively
permitting or obstructing the flow of blood through the venous blood line. The
pinch
valve is provided so as to pinch the venous blood line and thereby prevent the
flow of
blood back to the patient in the event that an unsafe condition has been
detected.
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[025] Preferably, the hemodialysis system contains sensors for monitoring
hemodialysis. To this end, preferably the dialysis machine has at least one
flow sensor
connected to the dialysate flow path for detecting fluid flow (volumetric
and/or velocity)
within the dialysate flow path. In addition, it is preferred that the dialysis
machine
contain one or more pressure sensors for detecting the pressure within the
dialysate flow
path, or at least an occlusion sensor for detecting whether the dialysate flow
path is
blocked. Preferably, the dialysis machine also possesses one or more sensors
for
measuring the pressure and/or fluid flow within the blood flow path. The
pressure and
flow rate sensors may be separate components, or pressure and flow rate
measurements
may be made by a single sensor.
[026] Furthermore, it is preferred that the hemodialysis system include a
blood leak
detector ("BLD") which monitors the flow of dialysate through the dialysate
flow path
and detects whether blood has inappropriately diffused through the dialyzer's
semipermeable membrane into the dialysate flow path. In a preferred
embodiment, the
hemodialysis system includes a blood leak sensor assembly incorporating a
light source
which emits light through the dialysate flow path and a light sensor which
receives the
light that has been emitted through the dialysate flow path. After passing
through the
dialysate flow path, the received light is then analyzed to determine if the
light has been
altered to reflect possible blood in the dialysate.
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[027] The dialysis machine preferably includes additional sensors including an
ammonia sensor and a pH sensor for detecting the level of ammonia and pH
within the
dialysate. Preferably, the ammonia sensor and pH sensor are in the dialysate
flow path
immediately downstream of the filter. In addition, the dialysis machine
possesses a
bubble sensor connected to the arterial blood line and a bubble sensor
connected to the
venous blood line for detecting whether gaseous bubbles have formed in the
blood flow
path.
[028] The hemodialysis system possesses a processor containing the dedicated
electronics for controlling the hemodialysis system. The processor contains
power
management and control electrical circuitry connected to the pump motors,
valves, and
dialysis machine sensors for controlling proper operation of the hemodialysis
system.
[029] It has been found that decreasing the flow rate of the dialysate through
the
dialysate flow path increases the capacity of the sorbent filter's zirconium
phosphate to
capture ammonium from urea. Because urea is high at the beginning of a
patient's
treatment and then decreases as it is removed during treatment, a constant
urea
concentration requires starting at a high flowrate and reducing it over the
course of the
treatment. Advantageously any losses of urea clearance from decreasing the
dialysate
flow rate can be compensated for by extending the duration of the dialysis
treatment.
Accordingly, in a preferred embodiment, the hemodialysis system's processor
includes
memory which stores one or more patient treatment plans by which a patient is
treated.
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In accordance with the patient treatment plan, the dialysate flow rate through
the
dialysate flow path is not static throughout treatment. Instead, the dialysate
flow rate
decreases throughout the patient's treatment. The decrease in dialysate flow
rate may be
incremental. Alternatively, the dialysate flow rate may be decrease in any
manner such
as linear, exponential, inverse, polynomial, or other relationship which
provides for
decreasing the dialysate flow rate over time.
[030] Specifically, each patient treatment plan includes a total time period
"T(total)" for
treating a patient which in turn comprises a plurality of time segments
including time
.. segment Ti, time segment T2, time segment T3, etc. The patient treatment
plan further
including a plurality of flow rates including at least a high flow rate which
operates for
time segment Ti, time segment T2, time segment T3, etc. As would be understood
by
those skilled in the art, where the decrease in dialysate flow rate is changed
slowly, such
as in a linear or polynomial manner, the time period for each time segment may
be
extremely small.
[031] Preferably, the dialysate treatment starts at a higher dialysate flow
rate between
400 to 800 ml/min and the ends at a lower flow rate between 100 to 500 ml/min.
More
preferably, the dialysis treatment starts at a higher dialysate flow rate
between 450 to 800
.. ml/min and the ends at a lower flow rate between 100 to 450 ml/min. In a
preferred
embodiment, the patient treatment plan lasts two - six hours and begins
treatment with a
dialysate flow rate of approximately 400 to 600 ml/min and decreases linearly
until
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ending at a flow rate between 200 to 300 ml/min. In still a more preferred
embodiment,
the patient treatment plan begins treatment with a dialysate flow rate of
approximately
500 ml/min and decreases linearly for four hours until ending at a flow rate
of 250
ml/min.
[032] The dialysis machine provides a hemodialysis system that is
transportable,
lightweight, easy to use, patient-friendly and capable of in-home use.
[033] In addition, the hemodialysis system provides an extraordinary amount of
control
and monitoring not previously provided by hemodialysis systems so as to
provide
enhanced patient safety.
[034] Moreover, the hemodialysis system maximizes the amount of urea that can
be
removed by the sorbent filter.
[035] Other features and advantages of the present invention will be
appreciated by
those skilled in the art upon reading the detailed description, which follows
with
reference to the Drawings.
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Brief Description of The Drawings
[036] FIG. 1 is a flow chart illustrating a first embodiment of the
hemodialysis system;
[037] FIG. 2 is the flow chart of FIG. 1 illustrating an embodiment where
dialysate
.. avoids the filter by flowing through the bypass flow path;
[038] FIG. 3 is the flow chart of FIG. 1 illustrating an embodiment where
dialysate
flows through the filter in a closed loop dialysate flow path incorporating a
first reservoir;
[039] FIG. 4 is the flow chart of FIG. 1 illustrating an embodiment where
dialysate
flows through the filter in a closed loop dialysate flow path incorporating a
second
reservoir;
[040] FIG. 5 is a flow chart illustrating a second embodiment of the
hemodialysis
system including a closed loop filter flow path which is filtering the fluid
in a first
reservoir; and
[041] FIG. 6 is a flow chart illustrating the second embodiment of the
hemodialysis
system shown in FIG. 5 wherein the filter flow path which is filtering the
fluid in a
.. second reservoir;
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[042] FIG. 7 is the flow chart illustrating an embodiment of the hemodialysis
system
where dialysate from an outside source is supplied to one of the system's
reservoirs, and
used dialysate is directed to a storage bag or to a drain;
.. [043] FIG. 8 is the flow chart illustrating the embodiment of the
hemodialysis system in
Fig. 7 wherein a sorbent filter has been introduced into the system to provide
a closed-
loop operation;
[044] FIG. 9 is a block diagram illustrating the blood pump, dialysate pumps,
and flow
.. sensor connected to the hemodialysis system's processor; and
[045] Fig. 10 is a graph illustrating a patient treatment plan with a
decreasing dialysate
flow rate;
.. [046] Fig. 11 is a graph illustrating a second patient treatment plan with
a decreasing
dialysate flow rate;
[047] Fig. 12 is a graph illustrating a third patient treatment plan with a
decreasing
dialysate flow rate; and
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[048] Fig. 13 is a graph illustrating a fourth patient treatment plan with a
decreasing
dialysate flow rate.
Detailed Description
[049] While the present invention is capable of embodiment in various forms,
as shown
in the drawings, hereinafter will be described the presently preferred
embodiments of the
invention with the understanding that the present disclosure is to be
considered as an
exemplification of the invention, and it is not intended to limit the
invention to the
specific embodiments illustrated.
[050] As best illustrated in FIGS. 1 - 8, the hemodialysis system includes a
blood flow
path 53 and a dialysate flow path 54. The hemodialysis system further includes
a
reusable dialysis machine and disposable components for performing
hemodialysis. The
blood flow path 53 includes an arterial blood line 1 for connecting to a
patient's artery for
collecting blood from a patient, and a venous blood line 14 for connecting to
a patient's
vein for returning blood to a patient. The arterial blood line 1 and venous
blood line 14
may be typical constructions known to those skilled in the art.
[051] The blood flow path 53 transports blood in a closed loop system by
connecting to
the arterial blood line 1 and venous blood line 14 to a patient for
transporting blood from
a patient through the dialyzer 8 and back to the patient. Preferably, the
hemodialysis
system includes a supply of heparin 6 and a heparin pump connected to the
blood flow
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path 1. The heparin pump delivers small volumes of heparin anticoagulant into
the blood
flow to reduce the risk of blood clotting in the machine. The heparin pump can
take the
form of a linearly actuated syringe pump, or the heparin pump may be a bag
connected
with a small peristaltic or infusion pump.
[052] The hemodialysis system includes a dialyzer 8 in the dialysate flow path
54 which
is of a construction and design known to those skilled in the art. Preferably,
the dialyzer
8 includes a large number of hollow fibers which form a semipermeable
membrane.
Suitable dialyzers can be obtained from Fresenius Medical Care, Baxter
International,
Inc., Nipro Medical Corporation, and other manufacturers of hollow fiber
dialyzers. Both
the blood flow path and dialysate flow path travel through the dialyzer 8
which possesses
an inlet for receiving dialysate, an outlet for expelling dialysate, an inlet
for receiving
blood from a patient, and an outlet for returning blood to a patient.
Preferably, the
dialysate flows in the opposite direction to the blood flowing through the
dialyzer with
the dialysate flow path isolated from the blood flow path by a semipermeable
membrane
(not shown). As illustrated in FIGS. 1 - 6 and as explained in greater detail
below, the
dialysate flow path 54 transports dialysate in a closed loop system in which
dialysate is
pumped from a reservoir (17 or 20) to the dialyzer 8 and back to the reservoir
(17 or 20).
Both the blood flow path 53 and the dialysate flow path 54 pass through the
dialyzer 8,
but are separated by the dialyzer's semipermeable membrane.
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[053] Preferably, the hemodialysis system includes three primary pumps (5, 26
and 33)
for pumping blood and dialysate. For purposes herein, the term "pump" is meant
to refer
to both the pump actuator which uses suction or pressure to move a fluid, and
the pump
motor for mechanically moving the actuator. Suitable pump actuators may
include an
impeller, piston, diaphragm, the lobes of a lobe pump, screws of a screw pump,
rollers or
linear moving fingers of a peristaltic pump, or any other mechanical
construction for
moving fluid as can be determined by those skilled in the art. Meanwhile, the
pump's
motor is the electromechanical apparatus for moving the actuator. The motor
may be
connected to the pump actuator by shafts or the like. In a preferred
embodiment, the
dialysate and/or blood flow through traditional flexible tubing and each of
the pump
actuators consist of a peristaltic pump mechanism wherein each pump actuator
includes a
rotor with a number of cams attached to the external circumference of the
rotor in the
form of "rollers", "shoes", "wipers", or "lobes" which compress the flexible
tube. As the
rotor turns, the part of the tube under compression is pinched closed (or
"occludes")
forcing the fluid to be pumped through the tube. Additionally, as the tube
opens to its
natural state after the passing of the cam fluid flow is induced through the
tube.
[054] The first and second primary pumps (26 and 33) are connected to the
dialysate
flow path for pumping dialysate through the dialysate flow path from a
reservoir (17 or
20) to the dialyzer 8 and back to the reservoir (17 or 20). A first pump 26 is
connected to
the dialysate flow path "upstream", (meaning prior in the flow path) from the
dialyzer 8
while the second pump 33 is connected to the dialysate flow path "downstream"
Date Recue/Date Received 2022-08-31
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(meaning subsequent in the flow path) from the dialyzer 8. Meanwhile, the
hemodialysis
system's third primary pump 6 is connected to the blood flow path. The third
pump 6,
also referred to as the blood pump, pumps blood from a patient through the
arterial blood
line, through the dialyzer 8, and through the venous blood line for return to
a patient. It is
preferred that the third pump 6 be connected to the blood flow path upstream
from the
dialyzer. The hemodialysis system may contain more or less than three primary
pumps.
For example, the dialysate may be pumped through the dialyzer 8 utilizing only
a single
pump. However, it is preferred that the hemodialysis system contain two pumps
including a first pump 26 upstream from the dialyzer 8 and a second pump 33
downflow
from the dialyzer 8.
[055] Preferably, the hemodialysis system contains one or more reservoirs (17
and 20)
for storing dialysate solution. Where the system includes two reservoirs, both
of the
reservoirs (17 and 20) may be connected simultaneously to the dialysate flow
path 54 to
form one large source of dialysate. Alternatively, the hemodialysis system
includes a
valve assembly 21 for introducing either, but not both, of the two reservoirs
(17 or 20)
into the dialysate flow path 54 to form a closed loop system for transporting
a dialysate
from one of the two reservoirs to the dialyzer and back to that reservoir.
After the
dialysate in a first reservoir 17 has been used, is no longer sufficiently
clean, or does not
possess appropriate chemical properties, the hemodialysis system's valve 21 is
controlled
to remove the first reservoir 17 from the dialysate flow path and substitute
the second
reservoir 20, which has fresh dialysate 75, into the dialysate flow path.
Thus, when one
Date Recue/Date Received 2022-08-31
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reservoir possesses contaminated dialysate 76, and the reservoir needs to be
emptied and
refilled with freshly generated dialysis fluid 75, dialysis treatment can
continue using the
other reservoir.
[056] In this manner, the hemodialysis system may switch between each
reservoir 17
and 20 times over the course of the treatment. Furthermore, the presence of
two
reservoirs as opposed to one reservoir allows for the measurement of the flow
rate for
pump calibration or ultrafiltration measurement, while isolating the other
reservoir while
it is being drained or filled. Though the reservoirs may be of any size as
required by
clinicians to perform an appropriate hemodialysis treatment, preferred
reservoirs have a
volume between 0.5 liters and 5.0 liters.
[057] The hemodialysis system also contains a sorbent filter (also referred to
herein as a
"filter") connected to the dialysate flow path 54 for removing toxins which
have
permeated from the blood plasma through the semipermeable membrane into the
dialysate. In a first embodiment, the filter 36 is connected to the dialysate
flow path 54
downstream from the dialyzer so as to remove toxins transferred by the
dialyzer into the
dialysate prior to the dialysate being transported to the reservoir. Filter
materials for use
with the dialysis machine are well known to those skilled in the art. For
example,
suitable materials include resin beds including zirconium-based resins.
Preferably, the
filter has a housing containing layers of zirconium oxide, zirconium phosphate
and
carbon. Acceptable materials are described in U.S. Patent No. 8,647,506 and
U.S. Patent
Date Recue/Date Received 2022-08-31
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Application Publication No. 2014/0001112. Other acceptable filter materials
can be
developed and utilized by those skilled in the art without undue
experimentation. The
filter housing may or may not include a vapor membrane capable of releasing
gases, but
not liquids, and particularly not the dialysate liquid flowing through the
filter.
[058] In the event that the hemodialysis system possesses a sorbent filter,
preferably the
dialysis flow path 54 incorporates safety features in the form of an ammonium
sensor 37
and a pH sensor 38. These sensors may be located immediately downstream of the
sorbent cartridge 36, or immediately downstream of the one or more reservoirs.
When
the sorbent filter 36 has been exhausted, the filter 36 may begin to release
ammonium
ions as a result of the filtering chemical reaction. At certain levels,
ammonium ions in the
dialysis fluid can harm the patient. Preferably, the ammonium ion sensor 37
measures the
quantity of ammonium ions in parts per million (ppm). When the measurement
reaches a
range of approximately 5 to 20 ppm, a warning state will be activated, and
treatment with
this dialysate is stopped. The dialysis fluid can be drained, and dialysis
treatment may
continue by using fresh dialysis fluid using the alternative reservoir.
Similarly, the pH
sensor 38 also acts as a safety feature and supports the measurement of
ammonium ions.
As the pH of the dialysis fluid changes, the equilibrium state of ammonia
(NH3) and
ammonium ions (NH4+) can change. If the pH of the dialysis fluid is measured
to be
outside the range of approximately 6.4 to 7.8 pH, a warning state can be
activated, and
the dialysis fluid in use can be drained.
Date Recue/Date Received 2022-08-31
22
[059] It is also preferred that the hemodialysis system possesses a reagent
bag 39 and
pump 40 for introducing reagents into the dialysate flow path 54 immediately
after the
sorbent filter 36. The reagent bag 39 holds a concentrated solution of salts
and ions to
reinfuse the filter dialysis fluid. Through the action of filtering waste, the
sorbent filter
36 also removes beneficial ions from the dialysis fluid, such as calcium and
salt. Before
the filtered dialysis fluid can be recirculated, it must be reinfused with
calcium and salts
so that the dialysis fluid does not draw these beneficial ions from the
patient's blood.
Preferably, the reagent bag 39 will hold between 1 and 3 liters of
concentrated reagent.
The reagent pump 40 can be any type of pump such as a peristaltic pump or
diaphragm
pump. To ensure that the hemodialysis system is introducing the proper amount
of salts
and ions into the dialysate, a conductivity sensor 41 may be positioned within
the
dialysate flow path 54 immediately after the reagent bag 39. The conductivity
sensor 41
serves as a safety feature, measuring the total dissolved solids of the
regenerated dialysis
fluid. In the event that the total dissolved solids are detected to not be
within a prescribed
range, the operation of the pump 40 can be increased or decreased, or
alternatively,
treatment can be stopped entirely. For example, if a fault state is detected
in the dialysis
fluid, then the fluid can be redirected by 3-way valves 29 and 32 through the
bypass path
30 so that dialysate does not meet the patient's blood in the dialyzer. More
specifically,
the 3-way valve 29 directs dialysis fluid to the dialyzer's inlet and the 3-
way valve 32
directs dialysate from the dialysate outlet back through the dialysate flow
path 54.
However, if a fault state is detected in the dialysis fluid, such as the
temperature being too
Date Recue/Date Received 2022-08-31
23
low or excessive ammonium ions are detected in the dialysate, then the
dialysis fluid is
redirected by 3-way valves 29 and 32 to bypass the dialyzer 8, through bypass
path 30.
[060] For the embodiment illustrated in FIGS. 1 - 4, the hemodialysis system
includes a
drain flow path 55 to dispose of waste dialysate from the reservoirs (17 and
20). In the
embodiment illustrated in the FIGS 1 - 4, the drain flow path 55 is connected
to both
reservoirs (17 and 20). Waste dialysate may drain through the drain flow path
5 through
a gravity feed, or the hemodialysis system may include a pump 44 of any type
as can be
selected by those skilled in the art to pump used dialysate to be discarded,
such as to a
traditional building sewer line 45.
[061] For the embodiment illustrated in FIGS. 1 - 4, the hemodialysis system
preferably
includes a source 46 of dialysate fluid to replenish each of the reservoirs 17
and 20.
Preferably, the source of dialysate fluid includes a supply of clean water 46
that is mixed
with reagents (48 and 50) to provide dialysate of desired properties. In a
preferred
embodiment, the supply of clean water 46 is provided by a reverse osmosis
("RO")
machine located adjacent to the device which produces clean water and then
adds
chemical concentrates to create the dialysate fluid. The fluid is supplied
through a "fresh
dialysate" flow path 56 to the reservoirs (17 and 20). Preferably, the
hemodialysis
system also includes a source of concentrated reagents (48 and 50) which may
be stored
in disposable bags. Preferably, the concentrated reagents contain one or more
of the
following: carbonate solution, bicarbonate solution, acid solution, lactate
solution, salt
Date Recue/Date Received 2022-08-31
24
solution. It is necessary to separate some of the reagents into two bags (48
and 50) to
prevent undesirable interactions or precipitation of solutes. The source of
concentrated
reagents (48 and 50) is connected by pumps (47 and 49) to the supply line 46.
The
activation of the pumps (47 and 49) introduces the concentrated reagents into
the supply
of water to provide dialysate to the reservoirs (17 and 20).
[062] As an alternative to using the sorbent filter 36, the hemodialysis
system includes a
supplemental "bypass" flow path 35 that selectively transports dialysis around
the sorbent
filter 36. The bypass flow path includes a 3-way valve 34 upstream of the
filter. The 3-
way valve 34 is switched to direct the dialysis fluid through sorbent filter
36, or
alternatively, the 3-way valve 34 is switched to direct dialysate through the
bypass flow
path 35 to avoid the sorbent filter 36. For example, if a sorbent filter is
not available, or
if the sorbent filter has become spent, or if a sorbent filter is not required
for a particular
patient treatment, then the 3-way valve 34 is switched to direct the dialysis
fluid down the
bypass flow path 35.
[063] In an alternative embodiment illustrated in FIGS. 5 and 6, the sorbent
filter 71 is
located outside of the closed loop dialysate flow path. The hemodialysis
system includes
a separate closed loop "filter" flow path 57 that selectively connects to
either one of the
two dialysate reservoirs 17 or 20, and the filter 71 is positioned in-series
in the closed
loop filter flow path 57. Preferably, the dialysis machine includes an
additional fluid
pump 58 for pumping contaminated dialysate through the filter flow path and
the filter
Date Recue/Date Received 2022-08-31
25
71. As illustrated in FIGS. 5 and 6, a preferred filter flow path 57 includes
a 3-way valve
43 which determines which reservoir is drained of contaminated dialysate. For
example,
FIG. 5 illustrates the 3-way valve 43 connecting reservoir 20, but not
reservoir 17, to the
filter flow path 57. FIG. 6 illustrates the 3-way valve 43 connecting
reservoir 17, but not
reservoir 20, to the filter flow path 57. The filter flow path may include a
pump 58, or
the dialysate may dispense contaminated dialysate from reservoirs 17 or 20
through a
gravity feed. In addition, preferably the filter flow path 57 includes a
pressure sensor 59,
a check valve 60, an ammonium sensor 69, and a pH sensor 70.
[064] This embodiment of the hemodialysis machine includes a system for
introducing
reagents into the filter flow path. As illustrated in FIGS. 5 and 6, the
filter flow path 57
may include a first reagent source 61 containing salts and a second reagent
source 65
containing bicarbonate and lactate solution. These reagents are introduced
into the filter
flow path using pumps 62 and 66, and mixers 63 and 67. Preferably the filter
flow path
also possesses safety features in the form an ammonium sensor 69 to ensure
that the filter
71 is not spent and introducing unacceptable ammonium ions into the dialysate,
and
conductivity sensors 64 and 68 which monitor whether the reagents have been
properly
introduced into the cleaned dialysate to provide the proper amounts of
beneficial ions.
Finally, the filter flow path 57 includes a pair of check valves 51 and 52
which are
.. opened or closed to ensure that the now cleaned dialysate is returned to
the reservoir from
which the contaminated dialysate had been drained from.
Date Recue/Date Received 2022-08-31
26
[065] FIG. 7 illustrates an embodiment of the hemodialysis system where the
system is
operated in a single pass mode. Dialysate is introduced to the machine through
the fresh
dialysate flow path to the reservoir 17 from a source of dialysate 46 which is
maintained
at a desired temperature by a heater 23. For this treatment, the dialysate
from the first
reservoir 17 is circulated through the dialyzer 8 using pumps 26 and 33.
Thereafter, used
dialysate is then directed to a receptacle for storing wastewater 55, or an
effluent drain.
Load cells 81 and 82 and/or level sensors 15 may be provided to measure the
source of
dialysate 46 and the resulting wastewater 55. Furthermore, the dialysate flow
path may
include a flow sensor 25, pressure sensors 27, and a sample port 79.
[066] FIG. 8 illustrates still an additional embodiment of the hemodialysis
system which
operates in recirculating mode where the dialysate flows in a closed-loop
system through
the sorbent filter 36. Like other embodiments, the blood flow path 53
transports blood in
a closed loop system by connecting to the arterial blood line 1 and venous
blood line 14
to a patient for transporting blood from a patient to the dialyzer and back to
the patient.
Dialysate is stored in a reservoir 17 with the level of dialysate measured by
a level sensor
15 and load cell 19, and the dialysate's temperature maintained by a heater
23. Dialysate
is recirculated through the dialyzer 8 and sorbent cartridge 36 using pumps 26
and 33.
Thereafter, the dialysate is sent back to the same reservoir 17 through the
dialysate flow
.. path 54.
Date Recue/Date Received 2022-08-31
27
[067] In the embodiment illustrated in FIG. 8, the dialysate flow path
includes a
degasser 80 positioned downstream of the sorbent filter 36. The sorbent filter
36, in turn,
has an air inlet having a filter 36a, pressure sensor, and pump 44. Sorbent
regeneration
degassing may be accomplished by introducing a stream of air through the air
inlet,
which is substantially free of CO2, into the regenerated dialysate.
Preferably, the pump
44 introduces the stream of air into the sorbent filter 36 at about the same
approximate
flowrate as the flowrate of the liquid through the dialysate flow path. The
combined air-
liquid fluid may then be exposed to a hydrophobic membrane within the degasser
80
where the gas is free to exit the system, but liquid continues to flow through
the dialysate
flow path.
[068] In the embodiment illustrated in FIG. 8, sources of chemical
concentrates 48 and
50 are provided which can be added to the fluid leaving the sorbent filter, as
necessary, to
maintain proper chemicals in the dialysate. Preferably, the first reagent
source 48
contains salts and a second reagent source 50 contains bicarbonate or
carbonate and
lactate solution. The chemical concentrates are introduced into the dialysate
flow path
using the chemical concentrate pumps 47 and 49 where the clean water and
chemical
concentrates are mixed with mixers 63 and 67. Again, the dialysate flow path
may
include a flow sensor 25, pressure sensors 27, and a sample port 79.
Preferably, the
dialysate flow path also includes a conductivity sensor 41 positioned between
the second
mixer 67 and reservoir 17, and includes an ammonia sensor 37, a pH sensor 38
and a
combined conductivity/temperature sensor 24 positioned between the reservoir
17 and
Date Recue/Date Received 2022-08-31
28
dialyzer 8. A control processor is connected to the various sensors and pumps
to control
the hemodialysis treatment. With reference also to FIGS. 9 ¨ 13, preferably
the control
processor causes the flow rate of the dialysate to decrease throughout the
treatment, as
described below.
[069] With reference still to FIGS. 1 - 8, the hemodialysis system preferably
possesses a
heater 23 thermally connected to the dialysate flow path or to reservoirs for
heating the
dialysate to a desired temperature. For example, in an embodiment illustrated
in FIGS. 1
- 6, a single heater 23 is thermally coupled to the dialysate flow path
downstream of both
reservoirs (17 and 20). However, the hemodialysis may include additional
heaters, and
the one or more heaters may be in different locations. For example, in an
alternative
embodiment, the hemodialysis system includes two heaters, with a single heater
thermally coupled to each reservoir. The one or more heaters are preferably
activated by
electricity and includes a resistor which produces heat with the passage of an
electric
current.
[070] In addition, the hemodialysis system possesses various sensors for
monitoring
hemodialysis, and in particular, the dialysate flow path and blood flow path.
To this end,
the hemodialysis system preferably has one or more flow sensors 25 connected
to the
dialysate flow path for detecting fluid flow (volumetric and/or velocity)
within the
dialysate flow path. In addition, it is preferred that the hemodialysis system
contain one
or more pressure, or occlusion, sensors (9 and 27) for detecting the pressure
within the
Date Recue/Date Received 2022-08-31
29
dialysate flow path. Preferably, the hemodialysis system also possesses one or
more
sensors for measuring the pressure (4 and 7) and/or fluid flow 11 within the
blood flow
path.
[071] Preferably, the hemodialysis system includes temperature sensors (22, 24
and 28)
for measuring the temperature of the dialysate throughout the dialysate flow
path. In
addition, the hemodialysis system possesses level sensors for detecting the
level of fluid
in the reservoirs (17 and 20). Preferred level sensors may include either
capacitive fluid
level sensors (15 and 18) embodiment, the weight, and therefore level of
dialysate, of
each reservoir 17 and 20 is measured by a level sensor (16 or 19) connected to
the
processor.
[072] Furthermore, it is preferred that the hemodialysis system includes a
blood leak
detector 31 which monitors the flow of dialysate through the dialysate flow
path and
detects whether blood has inappropriately diffused through the dialyzer's
semipermeable
membrane into the dialysate flow path.
[073] Preferably, the hemodialysis system also contains a first pinch valve 2
connected
to the arterial blood line 1 for selectively permitting or obstructing the
flow of blood
through the arterial blood line, and a second pinch valve 13 connected to the
venous
blood line 14 for selectively permitting or obstructing the flow of blood
through the
venous blood line. The pinch valves are provided so as to pinch the arterial
blood line 1
Date Recue/Date Received 2022-08-31
30
and venous blood line 14 to prevent the flow of blood back to the patient in
the event that
any of the sensors have detected an unsafe condition. Providing still
additional safety
features, the hemodialysis system includes blood line bubble sensors (3 and
12) to detect
if an air bubble travels backwards down the arterial line (blood leak sensor
3) or venous
line (blood leak sensor 12). Further, the blood flow path 53 may include a
bubble trap 10
which has a pocket of pressurized air inside a plastic housing. Bubbles rise
to the top of
the bubble trap, while blood continues to flow to the lower outlet of the
trap. This
component reduces the risk of bubbles traveling into the patient's blood.
[074] To control the flow and direction of blood and dialysate through the
hemodialysis
system, the hemodialysis system includes a variety of fluid valves for
controlling the flow
of fluid through the various flow paths of the hemodialysis system. The
various valves
include pinch valves and 2-way valves which must be opened or closed, and 3-
way
valves which divert dialysate through a desired flow pathway as intended. In
addition to
the valves identified above, the hemodialysis system includes a 3-way valve 21
located at
the reservoirs' outlets which determines from which reservoir (17 or 20)
dialysate passes
through the dialyzer 8. An additional 3-way valve 42 determines to which
reservoir the
used dialysate is sent to. Finally, 2-way valves 51 and 52 (which may be pinch
valves)
are located at the reservoirs' inlets to permit or obstruct the supply of
fresh dialysate to
.. the reservoirs 17 and 20). Of course, alternative valves may be employed as
can be
determined by those skilled in the art, and the present invention is not
intended to be
limited the specific 2-way valve or 3-way valve that has been identified.
Date Recue/Date Received 2022-08-31
31
[075] In addition, the hemodialysis system includes a processor 77 and a user
interface
(not shown). The processors contain the dedicated electronics for controlling
the
hemodialysis system including the hardware and software, and power management
circuitry connected to the pump motors, sensors, valves and heater for
controlling proper
operation of the hemodialysis system. The processor monitors each of the
various
sensors to ensure that hemodialysis treatment is proceeding in accordance with
a
preprogrammed procedure input by medical personnel into the user interface.
The
processor may be a general-purpose computer or microprocessor including
hardware and
software as can be determined by those skilled in the art to monitor the
various sensors
and provide automated or directed control of the heater, pumps, and pinch
valve. The
processor may be located within the electronics of a circuit board or within
the aggregate
processing of multiple circuit boards and memory cards.
[076] Also not shown, the hemodialysis system includes a power supply for
providing
power to the processor, user interface, pump motors, valves, and sensors. The
processor
is connected to the dialysis machine sensors (including reservoir level
sensors (15, 16, 18
and 19), blood leak sensor 31, ammonia sensor 37, pressure and flow rate
sensors (4, 7, 9,
11, 25 and 27), temperature sensors (22, 24 and 28), blood line bubble sensors
(3 and 12),
pumps (5, 6, 26, 33, 40, 44, 47 & 49), and pinch valves (2 and 13) by
traditional electrical
circuitry.
Date Recue/Date Received 2022-08-31
32
[077] In operation, the processor is electrically connected to the first,
second and third
primary pumps (5, 26, and 33) for controlling the activation and rotational
velocity of the
pump motors, which in turn controls the pump actuators, which in turn controls
the
pressure and fluid velocity of blood through the blood flow path and the
pressure and
fluid velocity of dialysate through the dialysate flow path. By independently
controlling
operation of the dialysate pumps 26 and 33, the processor can maintain,
increase, or
decrease the pressure and/or fluid flow within the dialysate flow path within
the dialyzer.
Moreover, by controlling all three pumps independently, the processor can
control the
pressure differential across the dialyzer's semipermeable membrane to maintain
a
.. predetermined pressure differential (zero, positive or negative), or
maintain a
predetermined pressure range. For example, most hemodialysis is performed with
a zero
or near zero pressure differential across the semipermeable membrane, and to
this end,
the processor can monitor and control the pumps to maintain this desired zero
or near
zero pressure differential. Alternatively, the processor may monitor the
pressure sensors
and control the pump motors, and in turn pump actuators, to increase and
maintain
positive pressure in the blood flow path within the dialyzer relative to the
pressure of the
dialysate flow path within the dialyzer. Advantageously, this pressure
differential can be
affected by the processor to provide ultrafiltration and the transfer of free
water and
dissolved solutes from the blood to the dialysate.
[078] In the preferred embodiment, the processor monitors the blood flow
sensor 11 to
control the blood pump flowrate. It uses the dialysate flow sensor 25 to
control the
Date Recue/Date Received 2022-08-31
33
dialysate flow rate from the upstream dialysate pump. The processor then uses
the
reservoir level sensors (15, 16, 18 and 19) to control the flowrate from the
downstream
dialysate pump 33. The change in fluid level (or volume) in the dialysate
reservoir is
identical to the change in volume of the patient. By monitoring and
controlling the level
in the reservoir, forward, reverse, or zero ultrafiltration can be
accomplished.
[079] With reference to FIGS. 3, 4, and 8 - 13, where the hemodialysis system
is
operating with the dialysate flowing in a closed loop through the sorbent
filter 36,
preferably the dialysate flow rate is reduced throughout a patient's
treatment. More
.. specifically, it has been discovered that greater urea can be removed
during treatment
using the same sorbent cartridge 36 if the duration of treatment is increased.
This is
illustrated in the table below which indicates that the same spKt/V can be
achieved with a
lower dialysate flow rate so long as the treatment period is extended. The
spKt/V is a
measure of adequacy for dialysis based on urea clearance (K) over time (t) and
on the
distributed urea volume (V) of a person. The KDOQI 2015 Clinical Practice
Guideline
for Hemodialysis Adequacy guideline 3.1 suggests a minimum Kt/V for thrice
weekly
dialysis of 1.2. The "sp" portion of spKt/V stands for "single pool" which in
practice
means it is calculated by assuming the human body is like a single volume of
fluid that
evenly holds and releases urea. This measure of dialysis effectiveness is
often related to
the initial and final blood urea nitrogen ("BUN") of a dialysis patient where
the final
BUN is measured as soon as dialysis is complete. Here, the same spKt/V can be
achieved with a 600 ml/min for 240 minutes as a treatment with a dialysate
flow rate at
Date Recue/Date Received 2022-08-31
34
300 ml/min for 285 minutes wherein the percentage change in spKt/V is measured
from
the baseline numbers shown in bold. However, the sorbent cartridge 36 is
capable or
absorbing more urea during treatment operated at the lower dialysate flow
rate.
35L Patient Distribution Volume 35L
Patient Distribution Volume %
A B C D A B C D
Treatment
Length 240min 255min 270min 285min 240min 255min 270min 285min
Dialysate
Flow
spKtN %
Change in spKt/V from baseline
Rate
(ml/min)
300 1.44 1.53 1.61 1.69 -16.0 -9.9 -4.8 0.0
400 1.57 1.66 1.76 1.86 -7.4 -1.8 4.1 9.6
500 1.64 NA NA NA -3.0
NA NA NA
600 1.69 NA NA NA 0.0 NA
NA NA
[080] In addition, as seen in the following table showing linear reductions in
dialysate
flow rate, for a dialysate flow rate of 500 - 300 ml/min in a 35L distributed
urea volume
patient, the spKt/V is 1.54. This is similar to the 1.57 spKt/V for a constant
flow rate of
400m1/min. Similarly, for a dialysate flow rate of 550 - 250 ml/min in a 35L
distributed
urea volume patient, the spKt/V is 1.52, which is still similar to the 1.57
spKt/V for a
constant flow rate of 400m1/min. This tells us that the average of the
dialysate flow rate
matters more than ramping the flow rate for affecting urea removal.
Date Recue/Date Received 2022-08-31
35
2 Dialysis Flow Rate Variation and Urea Clearance
240min Treatment, 3L Initial Volume
% Change in
spKt/V from
spKt/V baseline
Dialysate
FR Initial- 35L 40L 35L 40L
Final Patient Patient Patient Patient
(ml/min) Volume
Volume Volume Volume
600 to 600 1.69 1.52 0 0
600
O. 7 0 to 500 1.68 1.51 -0.6 -0.7
ml/min
800 to 400 1.66 1.5 -1.8 -1.3
Average
900 to 300 1.63 1.47 -3.6 -3.3
400 to 400 1.57 1.41 -7.4 -7.5
400
500 to 300 1.54 1.39 -9.3 -8.9
ml/min
550 to 250 1.52 1.36 -10.6 -11.1
Average
600 to 200 1.48 1.34 -13.2 -12.6
[081] But again, the sorbent cartridge 36 is capable of absorbing more urea
during
treatment operated at the decreasing dialysate flow rate. Also of importance,
urea is
typically released into the dialysate at greater levels at the beginning of a
hemodialysis
treatment compared to the end of treatment. Thus, a higher dialysate flow rate
at the
beginning of treatment is preferred. To balance these counteracting
influences, it is
preferred that a patient's treatment commence with the dialysate flowing at a
high flow
rate at the beginning of treatment, but that dialysate flow rate decrease
through a patient's
treatment.
Date Recue/Date Received 2022-08-31
36
[082] There are other reasons to change the dialysate flowrates over the
course of a
treatment besides optimizing urea removal in a sorbent filter. Balancing the
volume of
dialysate needed for a treatment with the length of a treatment can be
accomplished by
varying the dialysate flowrate over the course of the treatment. When the urea
concentration is high at the beginning of treatment, a high dialysate flowrate
is helpful in
quickly removing urea from the blood. As the urea concentration decreases,
decreasing
the flowrate does not overly change the urea that can be removed from the
blood, but the
amount of dialysate consumed can be decreased.
[083] To implement the patient treatment plan with decreasing dialysate flow
rate, the
processor 77 is connected to the dialysate flow sensor 25 to monitor the flow
of dialysate,
and the processor 77 is connected to the dialysate pumps 26 and 33 to control
the rate that
dialysate flows through the dialysate flow path. In addition, the processor 77
includes
memory 78 which stores one or more patient treatment plans by which a patient
is
treated. The patent treatment plan includes the desired flow rates that
dialysate is
intended to flow at different time segments throughout the patient's
treatment. As
illustrated in FIGS. 10 - 13, in accordance with the patient treatment plan,
the dialysate
flow rate decreases throughout the patient's treatment. The decrease in
dialysate flow
rate may be incremental, as illustrated in FIG. 11. Alternatively, the
dialysate flow rate
may decrease in linear manner as illustrated in FIG. 12. In still alternative
treatment
plans, the decrease in the dialysate flow rate may be exponential, inverse,
polynomial, or
another relationship which provides for decreasing the dialysate flow rate
over time. For
Date Recue/Date Received 2022-08-31
37
example, FIG. 12 illustrates an acceptable polynomial treatment protocol where
the rate
of change (A) of the decreasing flow rate is decreasing. Conversely, FIG. 13
illustrates
an acceptable polynomial treatment protocol where the rate of change (A) of
the
decreasing flow rate is increasing.
[084] Specifically, each patient treatment plan includes a total time period
"T(total)" for
treating a patient which in turn comprises a plurality of time segments
including time
segment Ti, time segment T2, time segment T3, etc. The patient treatment plan
further
includes a plurality of flow rates including at least a high flow rate which
operates for
time segment Ti. The treatment plan further includes time segment T2, time
segment
T3, etc. As would be understood by those skilled in the art, where the
decrease in
dialysate flow rate is changed substantially continuously, such as in a linear
or
polynomial manner, the time period for each time segment is considered to be
extremely
small.
[085] Preferably, the dialysis treatment starts at a higher dialysate flow
rate, such as
between 400 to 800 ml/min, and the ends at a lower flow rate between 100 to
500
ml/min. However, a dialysis treatment may start even above 800 ml/min and end
at a
lower flow rate than 100 ml/min. More preferably, the dialysis treatment
starts at a
higher dialysate flow rate between 450 to 800 ml/min and the ends at a lower
flow rate
between 100 to 450 ml/min. However, another patient may require a different
treatment
protocol. For example, in another preferred embodiment, the patient treatment
plan lasts
Date Recue/Date Received 2022-08-31
38
four hours and begins treatment with a dialysate flow rate of approximately
400 to 600
ml/min and decreases linearly until ending at a flow rate between 200 to 300
ml/min.
[086] In the preferred embodiment illustrated in FIGS. 10 - 13, the patient
treatment
plan begins treatment with a dialysate flow rate of approximately 500 ml/min
and
decreases linearly for two hours until ending at a flow rate of 250 ml/min.
However, the
treatment protocols may be different such as decreasing linearly, as
illustrated in FIG. 10,
or decreasing incrementally, as illustrated in FIG. 11. For example, for the
embodiment
illustrated in FIG. 11, a patient is treated initially for time segment Ti of
1.0 hours at a
high dialysate flow rate above 450 ml/min (illustrated at 500 ml/min), a
second time
segment T2 of 1.0 hours at an intermediate flow rate between 450 - 400 ml/min
(illustrated at 417 ml/min), a third time segment T3 of 1.0 hours at an
intermediate flow
rate between 350 - 300 ml/min (illustrated at 333 ml/min); and a final time
segment T4
of 1.0 hours at a low flow rate between 300 - 200 ml/min (illustrated at 250
ml/min). In
the alternative, to reduce the flow rate incrementally or linearly, the
decrease in flow rate
may decrease over time (-A), as illustrated in FIG. 12, or the decrease in
flow rate may
increase over time (+A), as illustrated in FIG. 13. For each of these examples
illustrated
in FIGS. 10 - 13, the dialysate flow rate begins at approximately 500 ml/min
and
decreases for four hours until ending at a flow rate of 250 ml/min. In
addition to the
different methods of decreasing the dialysate flow rate, the patient treatment
plan's total
treatment time T(total) may be determined as appropriate for each patient
(such as 2 - 8
Date Recue/Date Received 2022-08-31
39
hours), as may the high flow rate (such as 800 - 400 ml/min) and low flow rate
(500 - 200
ml/min).
[087] To maintain proper treatment of a patient, the processor monitors all of
the
various sensors to ensure that the hemodialysis machine is operating
efficiently and
safely, and in the event that an unsafe or non-specified condition is
detected, the
processor corrects the deficiency or ceases further hemodialysis treatment.
For example,
if the venous blood line pressure sensor 9 indicates an unsafe pressure or the
bubble
sensor 12 detects a gaseous bubble in the venous blood line, the processor
signals an
alarm, the pumps are deactivated, and the pinch valves are closed to prevent
further blood
flow back to the patient. Similarly, if the blood leak sensor 31 detects that
blood has
permeated the dialyzer's semipermeable membrane, the processor signals an
alarm and
ceases further hemodialysis treatment.
[088] The dialysis machine's user interface may include a keyboard or touch
screen (not
shown) for enabling a patient or medical personnel to input commands
concerning
treatment or enable a patient or medical personnel to monitor performance of
the
hemodialysis system. Moreover, the processor may include Wi-Fi or Bluetooth
connectivity for the transfer of information or control to a remote location.
Date Recue/Date Received 2022-08-31
40
[089] Hereinafter will be identified the various components of the preferred
hemodialysis system with the numbers corresponding to the components
illustrated in the
Figures.
1 Arterial tubing connection
2 Pinch valve, arterial line. Used to shut off the flow connection
with the
patient, in case of an identified warning state potentially harmful to the
patient.
3 Bubble sensor, arterial line
4 Pressure sensor, blood pump inlet
Blood pump
6 Heparin supply and pump
7 Pressure sensor, dialyzer input
8 Dialyzer
9 Pressure sensor, dialyzer output
Bubble trap
10a Bubble trap level sensor
10b Bubble trap level sensor
11 Flow sensor, blood Circuit
12 Bubble sensor, venous line
13 Pinch valve, venous line
14 Venous tubing connection
Primary level sensor, first reservoir
16 Secondary level sensor, first reservoir
17 First reservoir which holds dialysis fluid
Date Recue/Date Received 2022-08-31
41
18 Primary level sensor, second reservoir
19 Secondary level sensor, second reservoir
20 Second reservoir which holds dialysis fluid
21 3-way valve, reservoir outlet.
22 Temperature sensor, heater inlet.
23 Fluid heater for heating the dialysis fluid from approximately
room
temperature or tap temperature, up to the human body temperature of 37 C.
24 Combined conductivity and temperature sensor
25 Flow sensor, Dialysis Circuit
26 Dialysis pump, dialyzer inlet
27 Pressure sensor, Dialysis Circuit
28 Temperature sensor, dialyzer inlet
29 3-way valve, dialyzer inlet
30 Bypass path, dialyzer
31 Blood leak detector
32 3-way valve, dialyzer outlet
33 Dialysis pump, dialyzer outlet
34 3-way valve, sorbent filter bypass
35 Sorbent filter bypass path
36 Sorbent filter
36a Filter
37 Ammonium ion sensor.
38 pH sensor
Date Recue/Date Received 2022-08-31
42
39 Reagent bag holds a concentrated solution of salts and ions
40 Pump, sorbent filter reinfusion.
41 Conductivity sensor, sorbent filter outlet.
42 3-way valve, reservoir recirculation.
43 3-way valve, reservoir drain.
44 Pump, reservoir drain.
45 Drain line connection.
46 Fresh dialysate supply
47 Pump which delivers concentrated reagents from reagent bag into
fresh
dialysate flow path
48 Reagent bag which holds a concentrated reagent that is introduced
into fresh
dialysate flow path.
49 Pump which delivers concentrated reagents from reagent bag into
the water
line.
50 Reagent bag which holds a concentrated reagent that will be mixed
with
water to form dialysis fluid.
51 Pinch valve, first reservoir inlet.
52 Pinch valve, second reservoir inlet.
53 Blood flow path
54 Dialysate flow path
55 Drain flow path
56 Fresh dialysis flow path
57 Filter flow path
58 Pump, filter flow path
59 Pressure sensor, filter flow path
Date Recue/Date Received 2022-08-31
43
60 Check valve
61 Reagents ¨ salts
62 Pump, reagents
63 Mixer
64 Conductivity sensor
65 Reagents ¨ bicarbonate / lactate
66 Pump, reagents
67 Mixer
68 Conductivity sensor
69 Ammonium ion sensor
70 pH sensor
71 Sorbent filter
75 Fresh dialy sate
76 Contaminated dialysate
77 Control Processor
78 Control Processor Memory
79 Sample port
80 Degasser
81 Reagent level/weight sensor
82 Reagent level/weight sensor
[090] The hemodialysis system provides increased flexibility of treatment
options based
on the required frequency of dialysis, the characteristics of the patient, the
availability of
Date Recue/Date Received 2022-08-31
44
dialysate or water and the desired portability of the dialysis machine. For
all treatments,
the blood flow path 53 transports blood in a closed loop system by connecting
to the
arterial blood line 1 and venous blood line 14 to a patient for transporting
blood from a
patient to the dialyzer and back to the patient.
[091] With reference to FIG. 2, a first method of using the hemodialysis
system does
not require the use of a sorbent filter 36. Water is introduced to the machine
through the
fresh dialysate flow path 56 from a water supply 46 such as water supplied
through
reverse osmosis (RO). If needed, chemical concentrates 48 and 50 are added to
the clean
water using the chemical concentrate pumps 47 and 49. The mixed dialysate is
then
introduced to reservoirs 17 and 20. For this treatment, the dialysate 75 from
a first
reservoir is recirculated past the dialyzer 8 through bypass path 35 back to
the same
reservoir. When the volume of the reservoir has been recirculated once, the
reservoir is
emptied through the drain flow path 55 and the reservoir is refilled through
the fresh
dialysate flow path 56.
[092] Meanwhile, while the first reservoir is being emptied and refilled,
hemodialysis
treatment continues using the second reservoir (17 or 20). As illustrated in
FIG. 2, once
the processor has determined that all dialysate has recirculated once, or
determined that
the dialysate is contaminated, the processor switches all pertinent valves
(21, 42, 43, 51
and 52) to remove the first reservoir 20 from patient treatment, and inserts
the second
reservoir 17 into the dialysate flow path 54. The dialysate 75 from the second
reservoir
Date Recue/Date Received 2022-08-31
45
17 is recirculated past the dialyzer 8 through bypass path 35 and back to the
same
reservoir 17. This switching back and forth between reservoirs 17 and 20
continues until
the dialysis treatment is complete. This operation is similar, but not the
same, as
traditional single-pass systems because no sorbent filter is used.
[093] In a second embodiment illustrated in FIG. 3, the sorbent cartridge 36
filters the
dialysate after it has passed through the dialyzer 8. To this end, the
processor switches
the 3-way valve 34 to incorporate the sorbent cartridge 36 into the dialysate
flow path 54,
and the processor switches the various valve assemblies (21, 42, 43, 51 and
52) to utilize
reservoir 17 during dialysis treatment. Clean dialysate 75 is recirculated
through the
dialyzer 8 and sorbent cartridge 36, and thereafter the dialysate is sent back
to the same
reservoir 17 through the dialysate flow path 54. This recirculation continues
as
determined by the processor including, but not limited to, because the sorbent
cartridge
has been spent, or the dialysate fluid is contaminated, or ultrafiltration has
resulted in the
reservoir 17 becoming full and requiring that it be drained and refilled.
Meanwhile, in
the event the fluid in reservoir 20 is contaminated, it is drained through the
drain flow
path 45, and then the reservoir 20 is refilled using the fresh dialysate flow
path 56.
[094] As illustrated in FIG. 4, once the processor has determined that
continued use of
reservoir 17 for dialysis treatment is not appropriate, the processor switches
the various
valve assemblies (21, 42, 43, 51 and 52) to remove reservoir 17 from the
dialysate flow
path 54, and to instead insert reservoir 20 within the dialysis flow path for
dialysis
Date Recue/Date Received 2022-08-31
46
treatment. Clean dialysate 75 is recirculated through the dialyzer 8 and
sorbent filter 36
back to the same reservoir 20. Again, this recirculation continues using
reservoir 20, as
determined by the processor, until switching back to reservoir 17, or until
dialysis
treatment has been completed. While dialysis treatment continues using
reservoir 20,
contaminated fluid 76 in reservoir 17 is drained through the drain flow path.
Thereafter,
reservoir 17 is refilled using the fresh dialysate flow path 56. Like other
treatment
methods, this switching back and forth between reservoirs 17 and 20 continues
until the
dialysis treatment is complete.
[095] In still an additional embodiment illustrated in FIGS. 5 and 6,
hemodialysis
treatment is conducted in similar manner as illustrated in FIG. 2 in which the
sorbent
filter 36 is not utilized within the dialysate flow path 54. Though it is
possible to utilize
the filter 36 within the dialysate flow path 54, for this embodiment it is
preferred that the
dialysate 75 be directed through the bypass path 35 so as to avoid the sorbent
filter 36.
.. During treatment, the dialysate 75 from the first reservoir is recirculated
past the dialyzer
8 through bypass path 35 and directed back to the same reservoir. Even more
preferably
for this embodiment, the hemodialysis system does not include sorbent filter
36. Instead,
with reference to FIGS. 5 and 6, the hemodialysis system includes a single
sorbent filter
71 which is within a separate closed loop flow path referred to herein as the
filter flow
path 57. Though FIGS. 5 and 6 illustrate the hemodialysis system including two
sorbent
filters 36 and 71, the sorbent filter 36 within the dialysate flow path 54 is
optional and
does not need to be incorporated within this embodiment of the hemodialysis
system.
Date Recue/Date Received 2022-08-31
47
[096] Like the prior embodiments, dialysis treatment is implemented while
switching
back and forth between reservoirs 17 and 20. With reference to FIG. 5, while
dialysis
treatment uses the clean dialysate 75 in reservoir 17, the various valve
assemblies (21, 42,
43, 51 and 52) are switched to insert the second reservoir 20 into the closed
loop filter
flow path 57. The contaminated water 76 is drained from the reservoir 20
through pump
58 and pressure sensor 59. Thereafter the contaminated water 76 is filtered
through the
sorbent filter 71. Reagents 61 and 65 may be introduced into the filter flow
path using a
gravity feed or pumps 62 and 66. The reagents are mixed within the mixers 63
and 67
before the now cleaned dialysate is tested for compliance by conductivity
testers 64 and
68, ammonium sensor 69, and pH sensor 70. If testing shows the water is now
clean, it is
directed back to reservoir 20.
[097] With reference to FIG. 6, the processor continues to monitor the output
of the
various sensors including those within the dialysate flow path 54. Once the
water within
reservoir 17 has become contaminated, it is removed from the dialysate flow
path and
reservoir 20 is substituted in its place by once again switching all of the
pertinent valve
assemblies (21, 42, 43, 51 and 52). The dialysate 75 from the second reservoir
20 is
recirculated in the closed loop dialysate flow path 54 past the dialyzer 8 and
directed
back to the same reservoir. Meanwhile, the now contaminated water 76 in
reservoir 17 is
drained through pump 58 and pressure sensor 59 before being filtered through
the sorbent
filter 71. Again, reagents 61 and 65 may be introduced into the filter flow
path 57 where
Date Recue/Date Received 2022-08-31
48
the reagents are mixed within the mixers 63 and 67. The now clean dialysate is
tested for
compliance by conductivity testers 64 and 68, ammonium sensor 69 and pH sensor
70
before filling reservoir 17. This process of alternating reservoirs continues
until the
prescribed hemodialysis treatment is completed, or a fault is detected which
requires that
treatment be halted.
[098] Like embodiments illustrated in FIGS. 2, 3, 5 and 6, the embodiment
illustrated in
FIG. 7 operates in a single pass mode. Dialysate is introduced to the machine
through the
fresh dialysate flow path to the reservoir 17 from a source of dialysate 46
which flows
through the dialysate flow path to the dialyzer 8. Thereafter, used dialysate
is then
directed to a receptacle for storing wastewater 55, or an effluent drain.
Though not
requiring the use of a sorbent filter, this single pass mode typically
requires 400 - 600
liters of water.
[099] Conversely, the embodiment of the hemodialysis system illustrated in
FIG. 8
operates in a closed loop recirculating mode where the dialysate flows through
the
sorbent filter 36. Dialysate is stored in a reservoir 17 and recirculated
through the
dialyzer 8 and sorbent cartridge 36. Chemical concentrates 48 and 50 are added
to the
filtered water, as necessary. Recirculation continues as determined by the
processor until
treatment has completed, the sorbent cartridge has been spent, the dialysate
fluid is
contaminated, or ultrafiltration has resulted in the reservoir 17 becoming
full and
requiring that it be drained and refilled.
Date Recue/Date Received 2022-08-31
49
[100] In closing, regarding the exemplary embodiments of the present invention
as
shown and described herein, it will be appreciated that a hemodialysis system
is
disclosed. The principles of the invention may be practiced in a number of
configurations beyond those shown and described, so it is to be understood
that the
invention is not in any way limited by the exemplary embodiments, but is
generally
directed to a hemodialysis system and is able to take numerous forms to do so
without
departing from the spirit and scope of the invention. It will also be
appreciated by those
skilled in the art that the present invention is not limited to the particular
geometries and
materials of construction disclosed, but may instead entail other functionally
comparable
structures or materials, now known or later developed, without departing from
the spirit
and scope of the invention. Furthermore, the various features of each of the
above-
described embodiments may be combined in any logical manner and are intended
to be
included within the scope of the present invention.
[101] Groupings of alternative embodiments, elements, or steps of the present
invention
are not to be construed as limitations. Each group member may be referred to
and
claimed individually or in any combination with other group members disclosed
herein.
It is anticipated that one or more members of a group may be included in, or
deleted
from, a group for reasons of convenience and/or patentability. When any such
inclusion
or deletion occurs, the specification is deemed to contain the group as
modified.
Date Recue/Date Received 2022-08-31
50
[102] Unless otherwise indicated, all numbers expressing a characteristic,
item,
quantity, parameter, property, term, and so forth used in the present
specification and
claims are to be understood as being modified in all instances by the term
"about." As
used herein, the term "about" means that the characteristic, item, quantity,
parameter,
property, or term so qualified encompasses a range of plus or minus ten
percent above
and below the value of the stated characteristic, item, quantity, parameter,
property, or
term. Accordingly, unless indicated to the contrary, the numerical parameters
set forth in
the Specification and attached claims are approximations that may vary. At the
very
least, and not as an attempt to limit the application of the doctrine of
equivalents to the
scope of the claims, each numerical indication should at least be construed in
light of the
number of reported significant digits and by applying ordinary rounding
techniques.
Notwithstanding that the numerical ranges and values setting forth the broad
scope of the
invention are approximations, the numerical ranges and values set forth in the
specific
examples are reported as precisely as possible. Any numerical range or value,
however,
inherently contains certain errors necessarily resulting from the standard
deviation found
in their respective testing measurements. Recitation of numerical ranges of
values herein
is merely intended to serve as a shorthand method of referring individually to
each
separate numerical value falling within the range. Unless otherwise indicated
herein,
each individual value of a numerical range is incorporated into the present
Specification
as if it were individually recited herein.
Date Recue/Date Received 2022-08-31
51
[103] The terms "a," "an," "the" and similar referents used in the context of
describing
the present invention (especially in the context of the following claims) are
to be
construed to cover both the singular and the plural, unless otherwise
indicated herein or
clearly contradicted by context. All methods described herein can be performed
in any
suitable order unless otherwise indicated herein or otherwise clearly
contradicted by
context. The use of any and all examples, or exemplary language (e.g., "such
as")
provided herein is intended merely to better illuminate the present invention
and does not
pose a limitation on the scope of the invention otherwise claimed. No language
in the
present specification should be construed as indicating any non-claimed
element essential
to the practice of the invention.
[104] Specific embodiments disclosed herein may be further limited in the
claims using
consisting of or consisting essentially of language. When used in the claims,
whether as
filed or added per amendment, the transition term "consisting of" excludes any
element,
step, or ingredient not specified in the claims. The transition term
"consisting essentially
of' limits the scope of a claim to the specified materials or steps and those
that do not
materially affect the basic and novel characteristic(s). Embodiments of the
present
invention so claimed are inherently or expressly described and enabled herein.
[105] It should be understood that the logic code, programs, modules,
processes,
methods, and the order in which the respective elements of each method are
performed
are purely exemplary. Depending on the implementation, they may be performed
in any
Date Recue/Date Received 2022-08-31
52
order or in parallel, unless indicated otherwise in the present disclosure.
Further, the
logic code is not related, or limited to any particular programming language,
and may
comprise one or more modules that execute on one or more processors in a
distributed,
non-distributed, or multiprocessing environment.
[106] While several particular forms of the invention have been illustrated
and
described, it will be apparent that various modifications can be made without
departing
from the spirit and scope of the invention. Therefore, it is not intended that
the invention
be limited except by the following claims.
Date Recue/Date Received 2022-08-31
