U.S. patent application number 14/170601 was filed with the patent office on 2014-05-29 for method and device to treat kidney disease.
This patent application is currently assigned to MEDTRONIC, INC.. The applicant listed for this patent is Kimberly A. Chaffin, Carl Schu, Orhan Soykan. Invention is credited to Kimberly A. Chaffin, Carl Schu, Orhan Soykan.
Application Number | 20140148754 14/170601 |
Document ID | / |
Family ID | 45787352 |
Filed Date | 2014-05-29 |
United States Patent
Application |
20140148754 |
Kind Code |
A1 |
Soykan; Orhan ; et
al. |
May 29, 2014 |
METHOD AND DEVICE TO TREAT KIDNEY DISEASE
Abstract
The invention relates to a method and device for dialysis and or
bulk fluid removal by generating a fibrosis chamber within a body
cavity and performing dialysis or bulk fluid removal. An
implantable medical device is described having a fibrosis chamber
and a pump. A dialysis chamber and an optional electrodialysis unit
can further be provided. An additional controller uses sensory
feedback to regulate the fluid levels by altering the extracellular
fluid retention within the fibrosis chamber. This device can be
used for the treatment of patients with chronic kidney disease who
may also be suffering from cardiorenal syndrome and
hypertension.
Inventors: |
Soykan; Orhan; (Shoreview,
MN) ; Schu; Carl; (Plymouth, MN) ; Chaffin;
Kimberly A.; (Woodbury, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Soykan; Orhan
Schu; Carl
Chaffin; Kimberly A. |
Shoreview
Plymouth
Woodbury |
MN
MN
MN |
US
US
US |
|
|
Assignee: |
MEDTRONIC, INC.
Minneapolis
MN
|
Family ID: |
45787352 |
Appl. No.: |
14/170601 |
Filed: |
February 1, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13399910 |
Feb 17, 2012 |
8641659 |
|
|
14170601 |
|
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|
61444092 |
Feb 17, 2011 |
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Current U.S.
Class: |
604/28 |
Current CPC
Class: |
A61M 1/1678 20130101;
A61M 1/28 20130101; A61M 1/284 20140204; A61M 2205/04 20130101;
A61M 1/1696 20130101 |
Class at
Publication: |
604/28 |
International
Class: |
A61M 1/28 20060101
A61M001/28 |
Claims
1. A method, comprising the steps of: inducing a pressure
difference across the peritoneum of a patient to increase a total
volume of peritoneal fluid in an implanted medical device,
performing one or more steps selected from the group consisting of:
1) dialyzing the blood across the peritoneal membrane, wherein
peritoneal fluid is conveyed to a space inside of the implanted
medical device and then conveyed to a dialysis chamber having a
dialysate to reduce the concentration of waste components in the
peritoneal fluid conveyed to the implanted medical device; 2)
dialyzing the blood across the peritoneal membrane, wherein
peritoneal fluid is conveyed to an inside of the implanted medical
device and then contacted with a dialysis chamber having dialysate
to reduce the concentration of waste components in the peritoneal
fluid conveyed to the implanted medical device and using an
electrical potential to regenerate the dialysate; and 3) removing
excess fluid from the patient by removing at least part of the
fluid from the implanted medical device from the patient, and
inducing a pressure difference across the peritoneum to decrease
the total volume of fluid in the implanted medical device and
return fluid from inside the medical device to the patient.
2. The method of claim 1, further comprising the step of cleansing
the dialysate in a closed loop.
3. The method of claim 1, further comprising the step of directing
at least part of the peritoneal fluid to the patient's urinary
bladder.
4. The method of claim 1, wherein the dialysis chamber or an
electrodialyzer for using an electrical potential to regenerate the
dialysate is located extracorporeally.
5. The method of claim 4, wherein the electrodialyzer further
comprises an adjustable voltage generator to generate electrical
fields of varying magnitudes for selective removal of waste
components.
6. The method of claim 3, further comprising a pump to assist
and/or control flow of the peritoneal fluid through a catheter to
the patient's urinary bladder.
7. The method of claim 6, further comprising piezoelectric
vibrators placed adjacent to the catheter to reduce calcification
of the catheter.
8. The method of claim 1, further comprising regenerating the
dialysate from the dialysis chamber using a dialysate cleansing
unit.
9. The method of claim 8, wherein the dialysate cleansing unit
comprises sorbent packages.
10. The method of claim 9, wherein the sorbent packages are
replaceable.
11. The method of claim 1, further comprising supplying a fresh
supply of dialysate to the dialysate chamber.
12. The method of claim 1, wherein the implanted medical device
comprises a partially porous mesh that forms a fibrosis cage upon
implantation into a patient, the fibrosis cage defining a space for
accessing fluid from the patient.
13. The method of claim 12, wherein the mesh is treated with at
least one of a surface coating of fibrosis-inducing agents, and
extracellular matrix components to promote growth of fibrous
tissue.
14. The method of claim 12, wherein the implanted medical device
further comprises a pumping means for pumping fluid into and out of
the fibrosis cage.
15. The method of claim 12, wherein the fibrosis cage further
comprises a material impermeable to cells surrounding the partially
porous mesh.
16. The method of claim 14, wherein the pumping means is one
selected from the group consisting of a bellows pump, a peristaltic
pump, a pulsatile pump, an impeller pump, and a syringe pump, said
pump means positioned inside the partially porous mesh, outside the
partially porous mesh or adjacent to the partially porous mesh.
17. The method of claim 14, wherein the pumping means is regulated
to not exceed a maximum pressure difference of any one of 5, 15,
20, 25, 30, 35, 40, 45 and 50 mmHG, wherein the pressure difference
is a pressure difference between the inside of the fibrosis cage
and a peritoneal cavity of a patient.
18. The method of claim 1, wherein the implanted medical device
further comprises a controller for regulating the fluid volume of
the patient and adjusting a clearance rate of the patient.
19. The method of claim 1, wherein the implanted medical device
further comprises a means for sensing a fluid volume of the
patient, wherein the means for sensing fluid volume is an
electrical impedance plethysmography or an arterial pressure
measurement.
20. The method of claim 1, wherein the implanted medical device is
powered by any selected from the group consisting of an internal
battery, an externally coupled power source and a rechargeable
battery wherein the rechargeable battery is rechargeable by
wireless energy transfer.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is filed as a divisional of U.S.
Non-provisional patent application Ser. No. 13/399,910, filed Feb.
17, 2012. This application claims benefit of priority to U.S.
Provisional Patent Application Ser. No. 61/444,092, filed Feb. 17,
2011, which is incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The invention relates to a partially or fully implantable
medical device for dialysis or fluid removal from the peritoneum
that overcomes problems with fibrogenesis and infection. The
medical device has a partially porous mesh that forms a fibrosis
cage upon implantation into a patient, an optional dialysis chamber
inside the partially porous mesh or extracorporeally having an
inlet and an outlet, and a pumping means for pumping fluid out of
the fibrosis cage. The systems and methods of the invention
optionally include an implantable dialyzer and or electrodialyzer.
The invention further relates to methods of introducing a dialysate
directly into a patient and dialyzing blood intracorporeally or
extracorporeally.
BACKGROUND
[0003] Kidneys of the human body function to remove excess fluids
as well as some ions. The functional unit of the kidney is the
nephron. A nephron consists of a filtering unit of tiny blood
vessels called a glomerulus attached to a tubule. When blood enters
the glomerulus, it is filtered and the remaining fluid then passes
along the tubule. In the tubule, chemicals and water are either
added to or removed from this filtered fluid according to the
body's needs, and the final product is urine, which is
excreted.
[0004] In patients with chronic kidney disease, kidney function is
severely compromised. Chronic kidney disease (CKD), also known as
chronic renal disease, is a progressive loss in renal function over
a period of months or years. The most severe stage of CKD is End
Stage Renal Disease (ESRD), which occurs when the kidneys cease to
function. The two main causes of CKD are diabetes and high blood
pressure, which are responsible for up to two-thirds of the cases.
Heart disease is the leading cause of death for all people having
CKD. Excessive fluid can accumulate in patients suffering from
ESRD. The mortality rate of ESRD patients who receive traditional
hemodialysis therapy is 24% per year with an even higher mortality
rate among diabetic patients. Fluid accumulates in ESRD patients
because the kidneys can no longer effectively remove water and
other fluids from the body. The fluid accumulates first in the
blood and then accumulates throughout the body, resulting in
swelling of the extremities and other tissues as edema. This
accumulation of fluid causes increased stress on the heart, in turn
causing significant increases in blood pressure or hypertension,
which can lead to heart failure.
[0005] Although the population of patients afflicted with CKD grows
each year, there is no cure. Current treatments for CKD seek to
slow the progression of the disease. However, as the disease
progresses, renal function decreases, and, eventually, renal
replacement therapy is employed to compensate for lost kidney
function. Renal replacement therapy entails either transplantation
of a new kidney or dialysis.
[0006] Methods to treat kidney disease require the processing of
blood to extract waste components such as urea and ions. The
traditional treatment for kidney disease involves dialysis.
Dialysis emulates kidney function by removing waste components and
excess fluid from a patient's blood. This is accomplished by
allowing the body fluids, usually the blood, to come into the close
proximity with the dialysate, which is a fluid that serves to
cleanse the blood and actively remove the waste components and
excess water. During this process, the blood and dialysate are
separated by a dialysis membrane, which is permeable to water,
small molecules (such as urea), and ions but not permeable to the
cells. Each dialysis session lasts a few hours and may be repeated
as often as three times a week.
[0007] Traditional processes, such as dialysis, require
extracorporeal processing of body fluids. Once the blood is
purified, it is then returned to the patient. Although effective at
removing waste components from blood, dialysis treatments are
administered intermittently and, therefore, do not emulate the
continuous function of a natural kidney. Once the dialysis session
is completed, the fluid begins to accumulate again in the tissues
of the patient. The benefits of dialysis notwithstanding,
statistics indicate that three out of five dialysis patients die
within five years of commencing treatment. Studies have shown that
increasing the frequency and duration of dialysis sessions can
improve the survivability of dialysis patients. Increasing the
frequency and duration of dialysis sessions more closely resembles
the continuous kidney function sought to be emulated. However, the
extracorporeal processing of the body fluids increases the
discomfort, inconvenience and the costs associated with treatment.
There is also an additional risk of infection, which mandates that
the procedures be carried out under the supervision of trained
medical personnel.
[0008] Wearable dialysis units have been conceived in which the
various components of the dialysis unit are miniaturized and made
portable. The utility of these units remains limited due to the
requirement that the blood must be brought outside of the body for
filtering and due to the necessity for frequent servicing of the
parts.
[0009] An alternative to a wearable dialysis system is an
implantable dialysis device. With conventional implantable dialysis
devices, most of the components are implanted, and the blood does
not leave the patient's body. This type of unit suffers from
difficulties related to the need for surgery to replace the
internal parts, generally resulting from growth of tissue over the
surfaces of the device that are exposed to tissue fluids, which
results in reduced efficiency of the filtration.
[0010] Another clinical solution for kidney disease is peritoneal
dialysis. In peritoneal dialysis, dialysate is infused into the
peritoneal cavity. The peritoneal membrane serves as a natural
dialyzer, and waste components diffuse from the patient's
bloodstream across the peritoneal membrane into the dialysis
solution via an osmotic gradient. Under local anesthesia, a
many-eyed catheter is sutured in place in the peritoneum and a
sterile dressing is applied. The amount and the kind of dialysate
and the length of time for each exchange cycle vary with the age,
size, and condition of the patient. There are three phases in each
cycle. During inflow, the dialysate is introduced into the
peritoneal cavity. During equilibration (swell), the dialysate
remains in the peritoneal cavity. By means of osmosis, diffusion,
and filtration, the needed electrolytes pass via the vascular
peritoneum to the blood vessels of the abdominal cavity, and the
waste products pass from the blood vessels through the vascular
peritoneum into the dialysate. During the third phase (drain), the
dialysate is allowed to drain from the peritoneal cavity by
gravity. The dialysis solution is removed, discarded, and replaced
with fresh dialysis solution on a semi-continuous or continuous
basis. Patients are able to replace the fluid periodically and care
for the access ports. This particular treatment causes discomfort
due to excess amounts of fluid being pumped in and out of the
abdominal area and retrograde flow into the bloodstream, which can
increase fluid retention and the risk of infections. Further,
medication for pain may be necessary.
[0011] Peritoneal dialysis may result in several complications,
including perforation of the bowel, peritonitis, atelectasis,
pneumonia, pulmonary edema, hyperglycemia, hypovolemia,
hypervolemia, and adhesions. Peritonitis, the most common problem,
is usually caused by failure to use aseptic technique and is
characterized by fever, cloudy dialysate, leukocytosis, and
abdominal discomfort. There is a need for a dialysis system for
peritoneal dialysis and/or fluid removal that is safe and effective
and that markedly improves a patient's comfort and quality of life
over conventional systems and methods. It would be advantageous for
the system to be safe enough for continuous use and allow the
patient to carry out normal daily activities. Hence, there is an
unmet medical need to build a wearable or implantable medical
device to treat chronic kidney disease that can provide more
frequent or continuous treatment with less discomfort and a lower
risk of infection.
SUMMARY OF THE INVENTION
[0012] The invention is directed to a medical device for dialysis
within the peritoneum that can be partially or fully implanted.
Related medical systems and methods for intra-corporeal dialysis
are provided.
[0013] In one embodiment, a partially implantable medical device
has a partially porous mesh that forms a fibrosis cage upon
implantation into a patient, and a pumping means for pumping fluid
into and out of the fibrosis cage. In any embodiment, the pumping
means can be positioned inside the partially porous mesh, outside
the mesh or adjacent to the mesh.
[0014] In another embodiment, the medical device has a dialysis
chamber having an inlet and an outlet inside of a partially porous
mesh.
[0015] In another embodiment, the medical device has a pumping
means positioned inside the partially porous mesh, outside the mesh
or adjacent to the porous mesh.
[0016] In another embodiment, the medical device has a partially
porous mesh that forms a fibrosis cage upon implantation into a
patient, an electrodialyzer in fluid communication with a dialysis
chamber inside the partially porous mesh, and a pumping means for
pumping fluid into and out of the fibrosis cage.
[0017] In another embodiment, the medical device has a partially
porous mesh that forms a fibrosis cage upon implantation into a
patient, an electrodialyzer in fluid communication with a dialysis
chamber, and a pumping means for pumping fluid into and out of the
fibrosis cage.
[0018] In another embodiment, the medical device has a partially
porous mesh that forms a fibrosis cage upon implantation into a
patient, an electrodialyzer in fluid communication with a dialysis
chamber, and a pumping means for pumping fluid into and out of the
fibrosis cage, wherein the pumping means is located outside of the
fibrosis cage.
[0019] In another embodiment, the medical device has a partially
porous mesh that forms a fibrosis cage upon implantation into a
patient, a pump that is placed inside or outside of the partially
porous mesh to provide the pumping means for pumping the fluid out
of the fibrosis cage, and a catheter to bring the fluid out of the
body or a catheter to bring the fluid into the bladder.
[0020] In another embodiment, the medical device has a pumping
means located inside of the fibrosis cage.
[0021] In another embodiment, the medical device has a partially
porous mesh that forms a fibrosis cage upon implantation into a
patient, an electrodialyzer in fluid communication with a dialysis
chamber and the electrodialyzer outside the partially porous mesh,
and a pumping means for pumping fluid into and out of the fibrosis
cage.
[0022] In another embodiment, the medical device has a partially
porous mesh that forms a fibrosis cage upon implantation into a
patient, an electrodialyzer in fluid communication with a dialysis
chamber and the electrodialyzer outside the partially porous mesh
and the body of a patient, and a pumping means for pumping fluid
into and out of the fibrosis cage.
[0023] In another embodiment, the medical device has a means for
sensing a fluid volume of the patient, wherein the means for
sensing fluid volume is an electrical impedance plethysmography or
an arterial pressure measurement.
[0024] In another embodiment, the medical device has a means to
deliver fresh dialysate to the dialysis chamber.
[0025] In another embodiment, the medical device has a controller
for regulating the fluid volume of the patent and adjusting a
clearance rate of the patient.
[0026] In yet another embodiment, the medical device has a
partially porous mesh that forms a fibrosis cage upon implantation
into a patient, an electrodialyzer inside the partially porous
mesh, and a pumping means for pumping fluid into and out of the
fibrosis cage.
[0027] In a medical system of the invention, one embodiment has a
partially porous mesh that forms a fibrosis cage upon implantation
into a patient, a dialysis chamber inside the partially porous mesh
having an inlet and an outlet, a pumping means for pumping fluid
into and out of the fibrosis cage, a optional means for sensing a
fluid volume of the patient, an external dialysate cleanser, and a
controller such as a pump controller known to those of skill in the
art for regulating the fluid volume and adjusting a clearance rate
of the patient.
[0028] In another medical system of the invention, one embodiment
has a partially porous mesh that forms a fibrosis cage upon
implantation into a patient, an electrodialyzer in fluid
communication with a dialysis chamber inside the partially porous
mesh, a pumping means for pumping fluid into and out of the
fibrosis cage, a optional means for sensing a fluid volume of the
patient, and a controller for regulating the fluid volume and
adjusting a clearance rate of waste components in the patient.
[0029] In another embodiment, the medical device has a partially
porous mesh that forms a fibrosis cage upon implantation into a
patient, an electrodialyzer inside the partially porous mesh, and a
pumping means for pumping fluid into and out of the fibrosis
cage.
[0030] In another embodiment, the medical device has a pumping
means that is a bellows pump.
[0031] In another embodiment, the medical device has a pressure
sensor to determine a fluid pressure within the medical device.
[0032] In another embodiment, the medical device has a pumping
means that is powered by a rechargeable battery.
[0033] In another embodiment, the medical device has a pumping
means that is powered by a rechargeable battery rechargeable
through wireless energy transfer.
[0034] In another embodiment, the medical device has a dialysate
chamber formed in arrays or a layered form.
[0035] In another embodiment, the medical device has a catheter to
convey fluid from inside a dialysis chamber to the urinary bladder
of a patient.
[0036] In another embodiment, the fibrosis cage of the medical
device is positioned in an abdominal area of the patient, and in
front of the peritoneal membrane of the patient.
[0037] In another embodiment, the medical device has a fibrosis
cage having a porous opening facing the peritoneal membrane of the
patient.
[0038] In another embodiment, the medical device has an external
dialysate cleansing unit containing a sorbent capable of removing
waste components and ions from dialysate.
[0039] In another embodiment, the medical device has a pumping
means selected from the group consisting of the pumping means is
one selected from the group consisting of a bellows pump, a
peristaltic pump, a pulsatile pump and a syringe pump.
[0040] In another embodiment, the medical device has a pumping
means regulated to maintain a maximum pressure change of 25 mmHg
between the inside volume of a fibrosis cage of the medical device
and the peritoneal cavity of a patient.
[0041] In another embodiment, the medical device has a pumping
means regulated to not exceed a maximum pressure change of 25 mmHg
between the inside volume of a fibrosis cage of the medical device
and the peritoneal cavity of a patient.
[0042] In another embodiment, the medical device has a pumping
means regulated to not exceed a maximum pressure change of any
selected from 5, 15, 20, 25, 30, 35, 40, 45 and 50 mmHg, wherein
the pressure difference is a pressure difference between the inside
volume of a fibrosis cage of the medical device and the peritoneal
cavity of a patient.
[0043] In another embodiment, the medical device has an
electrodialyzer that applies an electrical field to concentrate
ions and waste components into a plurality of chambers using an
electrical potential.
[0044] In another embodiment, the medical device has an
electrodialyzer that is in fluid communication with the patient's
urinary bladder.
[0045] In another embodiment, the medical device has a means for
sensing fluid volume in a patient wherein the means for sensing
fluid volume is electrical impedance plethysmography or an arterial
pressure measurement.
[0046] In another embodiment, the medical device is used to remove
bulk fluid or excess fluid from a patient.
[0047] In another embodiment, the medical device has a dialysis
chamber and a pumping means that function to allow excess fluid
from a patient to be removed from the patient and expelled through
an outlet of the dialysis chamber.
[0048] In another embodiment, the medical device has a dialysis
chamber containing a membrane, wherein the membrane contacts
extracellular fluid or bodily fluids of a patient.
[0049] In another embodiment, the medical device has a dialysis
chamber in fluid communication with a fibrosis cage, wherein the
dialysis chamber is located outside of the fibrosis cage.
[0050] In another embodiment, the medical device has a dialysis
chamber in fluid communication with a fibrosis cage, wherein the
dialysis chamber is located outside of the body of a patient.
[0051] In another embodiment, the medical device has a dialysis
chamber, wherein a fresh supply of the dialysate is supplied to the
dialysis chamber.
[0052] In another embodiment, the medical device has a dialysis
chamber, wherein a fresh supply of the dialysate is supplied to the
dialysis chamber and a dialysate exiting an outlet of the dialysis
chamber is not contacted with a sorbent or a dialysate cleansing
unit.
[0053] In another embodiment, the medical device removes excess
fluids from patients having cardio-renal syndrome. The device has a
fibrosis cage, a pump within the cage, and a catheter leading to
the bladder. The medical device can also have electronics such as a
negative pressure sensor and a wireless charger. The medical device
can be self-contained and remove a few liters of fluid a day from a
patient.
[0054] In yet another embodiment, a method has the steps of
introducing a dialysate into a patient in need thereof, and
dialyzing bodily fluid or extracellular fluid intra-corporeally.
Other embodiments include the steps of inducing a pressure
difference across the peritoneum of a patient to increase the total
volume of fluid in an implanted medical device, dialyzing bodily
fluids or extracellular fluid across a membrane using dialysate
inside the implanted medical device, and inducing a pressure
difference across the peritoneum to decrease the total volume of
fluid in the implanted medical device. Still other embodiments
contemplate the step of cleansing the dialysate in a closed loop
cleaning process.
[0055] In another embodiment, a medical device is applied to the
use of treating a patient by performing a method of treatment,
wherein the medical device has a partially porous mesh that forms a
fibrosis cage upon implantation into the patient and the fibrosis
cage defining a space for accessing fluid from the patient, and the
method of treatment comprises inducing a pressure difference across
the peritoneum of a patient to increase a total volume of
peritoneal fluid in an implanted medical device and performing one
or more steps selected from the group consisting of: 1) dialyzing
the blood across the peritoneal membrane, wherein peritoneal fluid
is conveyed to a space inside of the implanted medical device and
then conveyed to a dialysis chamber having a dialysate to reduce
the concentration of waste components in the peritoneal fluid
conveyed to implanted medical device; 2) dialyzing the blood across
the peritoneal membrane, wherein peritoneal fluid is conveyed to an
inside of the implanted medical device and then contacted with a
dialysis chamber having dialysate to reduce the concentration of
waste components in the peritoneal fluid conveyed to the implanted
medical device and using an electrical potential to regenerate the
dialysate; and 3) removing excess fluid from the patient by
removing at least part of the fluid from implanted medical device
from the patient. The method of treating the patient further
includes inducing a pressure difference across the peritoneum to
decrease the total volume of fluid in the implanted medical device
and return fluid from inside the medical device to the patient.
[0056] In another embodiment, a device is applied to a use for
removing waste components or fluid, the device having a partially
porous mesh and a fibrosis forming surface defining a space for
accessing extracellular fluid and a pump for moving extracellular
fluid into and out of the space, the use including reducing the
concentration of waste components in extracellular fluid or
removing extracellular fluid.
[0057] In another embodiment, an implantable medical device has a
partially porous mesh and a fibrosis-forming surface forming a
fibrosis cage that defines a space for accessing a fluid, wherein
the device is capable of inducing a relative pressure difference
inside the fibrosis cage and can perform any one of conveying a
fluid to the space inside the implanted medical device and then
conveying the fluid to a dialysis chamber having a dialysate to
reduce the concentration of waste components in the fluid conveyed
to the implanted medical device; conveying a fluid to the space
inside the implanted medical device and then conveying the fluid to
a dialysis chamber having a dialysate to reduce the concentration
of waste components in the fluid conveyed to the implanted medical
device and using an electrical potential to regenerate the
dialysate; and removing excess fluid by removing at least part of
the fluid from the implanted medical device, and also inducing a
pressure difference to decrease the total volume of fluid in the
implanted medical device.
[0058] In additional embodiments, dialysis is performed across the
membrane using a pump. In yet another embodiment, the step of
expelling an effluent dialysate extra-corporeally is contemplated.
Still yet another embodiment has the step of dialyzing bodily
fluids or extracellular fluid using an electrical potential and
directing the effluent filtrate to the patient's bladder. Other
objects, features and advantages of the present invention will
become apparent to those skilled in the art from the following
detailed description. It is to be understood, however, that the
detailed description and specific examples, while indicating some
embodiments of the present invention are given by way of
illustration and not limitation. Many changes and modifications
within the scope of the present invention may be made without
departing from the spirit thereof, and the invention includes all
such modifications.
BRIEF DESCRIPTION OF THE DRAWINGS
[0059] FIG. 1 is a diagram of a partially implantable embodiment of
a medical system for removing fluid from the peritoneum of a
patient and conveying the fluid to the urinary bladder.
[0060] FIG. 2 is a partially implantable embodiment of a dialysis
system having an external dialysis unit.
[0061] FIG. 3 is a block diagram of a partially implantable
embodiment of the dialysis system having an external dialysate
cleansing unit.
[0062] FIG. 4 is a graphical illustration of the pressure, flow,
and volume relationship that exists during operation of the
dialysis system.
[0063] FIG. 5 is a block diagram of a fully implantable embodiment
of the dialysis system having an internal electrodialysis unit.
[0064] FIG. 6 shows the electrodialysis unit of FIG. 5 in greater
detail.
[0065] FIG. 7 shows an implantable embodiment of a medical system
for removing fluid from the peritoneum of a patient and conveying
the fluid to the urinary bladder.
[0066] FIG. 8 shows the implantable embodiment of FIG. 7 with a
wireless power supply unit for providing power to the medical
system.
[0067] FIG. 9 shows an exemplary cage formed from stainless steel
with poly(N,N-dimethylacrylamide) (PDMA) end caps and size shown
relative to a Japanese 100 yen coin.
[0068] FIG. 10 shows an exemplary cage formed from polyester with a
fibrotic capsule after implantation for a period of two weeks.
[0069] FIG. 11 shows an exemplary cage formed from steel wrapped in
polyvinyl alcohol (PVA) with a fibrotic capsule after implantation
for a period of two weeks.
[0070] FIG. 12 shows a plot of the diffusion of urea across a
polyester cage with a fibrotic capsule and across a stainless steel
cage with a fibrotic capsule.
[0071] FIG. 13 shows a plot of the diffusion of potassium ions
across a stainless steel cage wrapped in polyvinyl alcohol (PVA)
with a fibrotic capsule.
DETAILED DESCRIPTION OF THE INVENTION
[0072] 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.
[0073] 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.
[0074] An "adjustable voltage generator" is an electrical component
capable of delivering and maintaining varying magnitudes of voltage
to other electronic components. The voltage delivered may be
determined by a user, or a programmable control unit.
[0075] A "bellows pump" is a pump capable of creating an
alternating positive and negative pressure within a confined
space.
[0076] "Chronic kidney disease" (CKD) is 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. Chronic kidney
disease 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 completely.
[0077] 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.
[0078] 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.
[0079] The term "consisting of" includes and is limited to whatever
follows the phrase the phrase "consisting of." Thus, the phrase
indicates that the limited elements are required or mandatory and
that no other elements may be present.
[0080] A "control system" consists of combinations of components
that act together to maintain a system to a desired set of
performance specifications. The performance specifications can
optionally include sensors and monitoring components, processors,
memory and computer components configured to interoperate.
[0081] A "controller" or "control unit" 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, which can be affected by adjusting certain
input variables.
[0082] The term "dialysate" describes a fluid into which solutes
from a fluid to be dialyzed diffuse through a membrane.
[0083] "Dialysis" is a type of filtration, or a process of
selective diffusion through a membrane. In certain embodiments,
dialysis removes solutes of a specific range of molecular weights
via diffusion through a membrane from a fluid to be dialyzed into a
dialysate. In other embodiments, dialysis can remove an amount of
bulk fluid volume from a subject or patient by passage of fluid
through a membrane due to a pressure difference across the
membrane; the pressure difference can be created by a pump in some
embodiments. In certain embodiments, bulk fluid volume can be
removed from the blood or extracellular fluid to affect fluid
removal from the patient or subject. 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 such
as ions, urea, and other small molecules are transported across the
filter membrane by diffusion between the fluids or a volume of
fluid crosses from one side of the membrane to the other. The
dialysate can be used to remove solutes and/or bulk fluid volume
from the fluid to be dialyzed, and does not necessarily require the
removal of waste via diffusive dialysis.
[0084] A "dialysis chamber" as used herein is a chamber in which
dialysis is performed. A dialysis chamber contains or has a
dialysis membrane for the performance of "dialysis" as defined
above. The dialysis membrane can be provided in any useful
configuration known to those of ordinary skill in the art including
provided as an arrangement of several hollow fibers, tubes,
microfibers or microtubes to maximize a ratio between surface area
of the dialysis membrane and a volume of dialysate. The dialysis
membrane can refer to a semi-permeable barrier selective to allow
diffusion of solutes of a specific range of molecular weights
through the barrier, or optionally a high-permeability membrane,
which is a type of semipermeable membrane that is more permeable to
water than the semipermeable membrane of a conventional dialysis
membranes having a semipermeable membrane that has a relatively low
permeability to water. In certain non-limiting examples, the
high-permeability semipermeable membrane has an in vitro filtration
coefficient (Kuf) greater than 8 milliliters per hour per
conventional millimeter of mercury, as measured with bovine or
expired human blood while a conventional semipermeable membrane has
a filtration coefficient (Kuf) less than 8 milliliters per hour per
convention millimeter of mercury. One of ordinary skill in the art
will understand that alternative and various configurations,
materials and values in performance and fabrication of the
dialysate chamber and/or membrane can be made and used without
departing from the invention.
[0085] An "electrodialysis unit" as used herein is a fluid
processing unit that removes waste components from effluent
dialysate by altering the ionic composition of a fluid. Such units
may include electrically conductive plates separated by
ion-exchange membranes. Fluid flowing between the plates is exposed
to an electrical field. The electrical field induces a rate of ion
movement within the fluid corresponding to the magnitude of the
voltage potential formed between the electrically conductive
plates.
[0086] A "dialysate cleansing unit" as used herein is a fluid
processing unit that removes waste components from effluent
dialysate via sorbent adsorption.
[0087] The term "effluent dialysate," as used herein describes the
discharge or outflow after the dialysate has been used for
dialysis.
[0088] A "fibrosis cage(s)" as used herein describes a fibrogenic
mesh encased in fibrotic tissue and having an empty internal cavity
containing the components of the implantable medical device as well
as bodily fluids.
[0089] The term "filtration" refers to a process of separating
solutes from a fluid, by passing the fluid through a filter medium
across which the solutes cannot pass.
[0090] The term "implantable," as used herein describes a device,
component or module intended to be totally or partially introduced,
surgically or medically into a mammalian body, or by medical
intervention that remains after the procedure.
[0091] The term "hyperosmotic" pertains to a solution that has a
higher solute concentration than another solution. In the human
body, a hyperosmotic state refers to a condition caused by the
accumulation in the body of significant quantities of osmotically
active solutes.
[0092] The term "hypoosmotic" pertains to a solution containing a
lower concentration of osmotically active components than a
standard solution. In the human body, a hypoosmotic state describes
a cell that has a lower concentration of solutes than its
surroundings.
[0093] The term "intracorporeal," as used herein means existing
within the body.
[0094] 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.
[0095] The term "mesh" or "porous mesh" refers to a porous
substructure that can be optionally wrapped in a material that
blocks the passage of cells. The "mesh" or "porous mesh" creates or
defines an acellular space or substantially acellular space within
the body of the patient, where the "mesh" or "porous mesh" allows
for the passage or diffusion of ions, urea and other small
molecules, and water while substantially preventing the passage of
cells. The "mesh" or "porous mesh" creates or defines an acellular
space from which fluid can be removed from the patient or fluid
from the peritoneum can be treated by dialysis or
electrodialysis.
[0096] A "patient" 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.
[0097] A "pressure gauge" is a device that measures pressure, which
is the force per unit area applied in a direction perpendicular to
the surface of an object. Gauge pressure is the pressure relative
to the local atmospheric or ambient pressure.
[0098] The term "programmable" as used herein refers to a device
using computer hardware architecture and being capable of carrying
out a set of commands, automatically.
[0099] The term "sensory unit" refers to an electronic component
capable of measuring a property of interest.
[0100] The term "total volume of fluid" refers to the total volume
of extracellular fluid and dialysate within the medical device or
fibrosis cage. The total volume of fluid can be controlled, in some
embodiments, through a pump or pump means that modifies the volume
of space accessible to extracellular fluid and/or dialysate within
the medical device or fibrosis cage. Specifically, in some
embodiments, a pump or pump means can increase the volume of space
to affect an influx of dialysate and/or extracellular fluid within
the medical device or fibrosis cage and a pump or pump means can
decrease the volume of space to affect an efflux of dialysate
and/or extracellular fluid from the medical device.
[0101] The terms "treating" and "treatment" refer to the management
and care of a patient having a pathology or condition. Treating
includes administering one or more embodiments of the present
invention to prevent or alleviate the symptoms or complications or
to eliminate the disease, condition, or disorder. 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.
[0102] The term "waste components" as used herein describe waste
organic and inorganic components, such as urea, uric acid,
creatinine, chlorides, inorganic sulfate and phosphate. Specific
"waste components" can vary between individual 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.
[0103] A "wearable dialyzer" is a portable artificial kidney device
through which blood is circulated as the user moves through his
daily routine, the dialyzing fluid being regenerated by a system of
filters and make-up solids continuously fed to the dialysis fluid.
The device may be a continuously internally operable and externally
regenerable dialysis device that is capable of concurrently
dialyzing a confined dialysis fluid against body fluids within the
body and regenerating the dialysis fluid outside the body.
Implantable Peritoneal Cage
[0104] The present invention can be used for the treatment of
chronic kidney disease, either as a replacement for a failed organ,
or to reduce the need for dialysis. Furthermore, it can be
configured to work as a stand-alone system wherein ambulatory
dialysis is carried out by the system, or as an auxiliary system
for hospital dialysis systems.
[0105] The present invention can employ a fibrosis cage, a pumping
means, and an optional dialysis chamber. Further, the present
invention can optionally employ a sensory unit, a controller, and
an electrodialysis unit.
[0106] Referring to FIG. 1, an embodiment of a system for removing
fluid from the body of a patient is described. A fibrosis cage 1 is
formed by implanting a partially porous fibrogenic mesh 1 into a
patient's body 2. The mesh can be treated with a surface coating of
fibrosis-inducing agents, or extracellular matrix components which
promote the growth of fibrous tissue. The mesh can also be covered
with a material that is impermeable to cells, such as a sheet of
polyvinyl alcohol (PVA). The mesh can also be impregnated with a
slow-release pharmacological agent which controls fibrous tissue
growth. For example, pharmacological agents that promote or inhibit
fibrous tissue growth can be used. The fibrosis cage is preferably
located in the patient's abdominal area, in front of the peritoneal
membrane 3. During a maturation period after implantation, the
fibrogenic mesh 1 promotes the growth of a fibrous tissue (shown
below) which encapsulates the mesh thereby forming the fibrosis
cage. The fibrosis cage has a porous opening facing the peritoneal
membrane 3 through which extracellular fluid enters the cage. The
peritoneal membrane 3 is represented by a dashed line in FIG. 1 to
illustrate the boundary between the peritoneal fluid and the blood
of the patient. After the maturation period, a space inside the
fibrosis cage is mostly void of cellular matter, and is full of
extracellular fluid from the peritoneum. Such cellular matter
includes red blood cells, white blood cells, polymorphonuclear
neutrophils, macrophages, and lymphocytes.
[0107] As illustrated in FIG. 1, in order to expedite the diffusion
of fluid in and out of the cage, a pump or pumping means 7 is
provided. The pump or pumping means 7 is not limited to any
particular type of pump or any particular location. In certain
embodiments, the pump or pumping means 7 is located outside of the
cage 1. In some embodiments, the non-limiting pump or pumping means
7 can be a bellows pump, a peristaltic pump, a syringe pump or a
pulsatile pump. The pump or pumping means 7 forces fluid in and out
of the cage periodically via expansion and contraction or another
pumping mechanism. The pump or pumping means 7 can be driven by an
implanted rechargeable battery, or an externally supplied magnetic
field. In certain embodiments, the rechargeable battery is
rechargeable by wireless energy transfer. An optional pressure
gauge can be present to monitor the fluid pressure within the
fibrosis cage. A controller 18 can be present to control the
operation of the pump or pumping means 7. The controller 18 can in
certain embodiments be located outside the body 2 of the patient
and can communicate with the pump or pumping means 7
wirelessly.
[0108] In certain embodiments, the pump or pumping means 7 is
located inside of the peritoneal cage. The pump or pumping means 7
can be provided in locations outside of the fibrosis cage. In some
embodiments the pumping means 7 can be placed adjacent to the cage
in a manner where the pump or pumping means 7 can modulate the
pressure within the fibrosis cage. In other embodiments, the pump
or pumping means 7 can be connected to the fibrosis cage through
any suitable means. In still other embodiments, the pump or pumping
means 7 can be connected to the cage with tubing. The pump or
pumping means 7 can optionally be connected to a catheter entering
into the urinary bladder.
[0109] In FIG. 1, fluid is removed from the patient by means of the
pump or pumping means 7 drawing extracellular fluid from the
peritoneum of the patient into the cage 1 and transporting at least
part of the fluid drawn into the cage 1 to the urinary bladder 20
by means of a catheter 22 connecting the cage 1 and the urinary
bladder 20. As such, fluid can be removed from the patient using an
implantable system without the need for providing a supply of
dialysate. In an alternate embodiment, the catheter 22 or another
means can be used to remove fluid from the cage 1 extracorporeally
without discharge to the bladder 20. That is, the catheter 22 or
equivalent structure can pass out of the body through a port or
incision such that fluid is discarded or collected outside of the
body.
[0110] Referring to FIG. 2, a fibrosis cage 1 as in FIG. 1 is
formed by implanting a partially porous fibrogenic mesh 1 into a
patient's body 2. In FIG. 2, the system is provided to perform
dialysis on the patient's blood via the peritoneal fluid. The
system in FIG. 2 has a dialysis chamber with a membrane for
performing dialysis, wherein fluid from the peritoneum via the
implanted cage 1 is contacted with one side of the membrane and a
dialysate is contacted with the other side of the membrane. Waste
components diffuse across the membrane inside the dialysis chamber
from the peritoneum to the dialysate. The fluid from the peritoneum
having a reduced concentration of waste components is returned to
the peritoneum cavity 24. Due to the removal of waste components
from the peritoneal fluid, waste components diffuse from the blood
of the patient across the peritoneum membrane 3. That is, the
system shown in FIG. 2 removes waste components from the peritoneum
fluid to maintain a concentration gradient in waste components
between the patient's blood and the peritoneal fluid across the
peritoneal membrane 3.
[0111] As shown in FIG. 2, a dialysis unit 30 is provided
extracorporeally in fluid communication with the implanted cage 1.
An outlet tube 34 is present connecting the dialysis unit 30 and an
outlet 36 of the implanted cage 1. Similarly, an inlet tube 38 is
present connecting the dialysis unit 30 and an inlet 32 of the
implanted cage 1. Outlet tube 34 and inlet tube 38 enter the body
through an incision or port 40 located on the body 2 of the
patient. The dialysis chamber (not shown) can be present inside the
dialysis cage 1 or the dialysis unit 30. In certain embodiments
where the dialysis chamber is present in the implanted cage 1, the
pump or pumping means 7 causes the influx and outflux of fluid from
the peritoneum into the implanted cage 1 and the dialysis unit 30
provides a dialysate that is moved through the dialysis chamber
inside the implanted cage 1. Due to the contact of the peritoneum
fluid and the dialysate across the membrane in the dialysis
chamber, waste components diffuse from the peritoneum of the
patient to the dialysate. Further, a hydrostatic pressure
difference across the membrane can cause the removal of fluid from
the peritoneum and the patient. The dialysis unit 30 provides a
source of dialysate including optionally a pump or other means to
convey dialysate through the dialysis chamber. A supply of fresh
dialysate can be provided wherein spent dialysate is discarded
after passage through the dialysis chamber or a dialysate cleansing
unit (described below) can be provided within the dialysis unit 30
to regenerate fresh dialysate from the dialysate exiting the cage 1
through outlet 36.
[0112] In other embodiments of the system shown in FIG. 2, the
dialysis chamber is located within the dialysis unit 30. In such
embodiments, peritoneal fluid is drawn into the implanted cage 1
through action of the pump or pumping means 7, which can be
positioned intra- or extracorporeally. The peritoneal fluid is
directed through outlet 36 and into outlet tube 34 to the dialysis
unit 30 and dialysis chamber wherein the peritoneal fluid removed
from the patient is dialyzed with a dialysate. The peritoneal fluid
removed from the patient via the implanted cage 1 is then returned
to the patient through the inlet tube 38 and inlet 32. Optionally,
at least part of the peritoneal fluid removed from the patient can
be discarded and not returned to the patient in order to cause a
net removal of fluid from the patient. A supply of fresh dialysate
can be provided wherein spent dialysate is discarded after passage
through the dialysis chamber or a dialysate cleansing unit
(described below) can be provided within the dialysis unit 30 to
regenerate fresh dialysate from previously used dialysate. As
described below, in any embodiment an electrodialysis unit can be
provided to regenerate effluent dialysate from the dialysis
chamber.
[0113] Referring to FIG. 3, an embodiment of a dialysis system
according to the present invention having an optional external
dialysate cleaning unit and a dialysis chamber within the implanted
cage 1 is described. In some embodiments, a supply of fresh
dialysate can be supplied in lieu of the optional external
dialysate cleaning unit. A fibrosis cage is formed by implanting a
partially porous fibrogenic mesh 1 into a patient's body 2. The
mesh can be treated with a surface coating of fibrosis-inducing
agents, or extracellular matrix components which promote the growth
of fibrous tissue. The mesh can also be covered with a material
that is impermeable to cells, such as a sheet of polyvinyl alcohol
(PVA). The mesh can also be impregnated with a slow-release
pharmacological agent that controls fibrous tissue growth. For
example, pharmacological agents that promote or inhibit fibrous
tissue growth can be used. The fibrosis cage is preferably located
in the patient's abdominal area, in front of the peritoneal
membrane 3. During a maturation period after implantation, the
fibrogenic mesh 1 promotes the growth of a fibrous tissue 6 which
encapsulates the mesh thereby forming the fibrosis cage. The
fibrosis cage has a porous opening 4 facing the peritoneal membrane
3 through which extracellular fluid enters the cage. After the
maturation period, a space 5 inside the fibrosis cage is mostly
void of cellular matter, and is full of extracellular fluid. Such
cellular matter includes red blood cells, white blood cells,
polymorphonuclear neutrophils, macrophages, and lymphocytes. An
alternative location to the abdominal area for the cage is inside
the peritoneal cavity, which itself has low number of cells, thus
rendering space 5 of the cage with even less cellular matter
therein.
[0114] In certain embodiments, the fibrosis cage can be formed by
two layers of materials. The first layer of material can be a metal
or a plastic configured into a substructure that provides
structural integrity to the overall device. The substructure is
formed into any configuration such that passage of fluid through
the substructure is unimpeded while the structural integrity of the
substructure is maintained. In certain non-limiting embodiments,
the substructure is formed into a mesh, a honey-comb, or any
arrangement of evenly or unevenly spaced openings between which
fluids can flow. Additionally, the first layer of material can be
formed into a cage that prevents the collapse of the device under
the pressure from the organs of the body. The substructure also
allows the device to be able to sustain a negative pressure in the
inner cavity of the device. The second layer of material is
optional and can be a coating used to cover the fibrosis cage.
Since the coating may not have a requisite structural strength, the
coating can rely on the substructure to remain in place over the
substructure. Due to the contact of the coating with tissue, the
biocompatibility of the coating material is important. In
particular, the coating material should not cause very thick
fibrosis, should allow for the passage of fluids and ions, and
should remain impermeable to the passage of cells. Many suitable
materials known to those of ordinary skill can be used for the
coating such as dialysis bags and woven polyesters. One
particularly preferred material is poly vinyl alcohol (PVA) foam. A
suitable, non-limiting thickness for a coating constructed from a
PVA foam can be from about 1 mm to about 10 mm.
[0115] To demonstrate the feasibility of accessing bodily fluids
using a fibrosis cage, a rodent model was implanted with stainless
steel or polyester cages. Stainless steel cages were built in the
shape of cylinders with a diameter of 1 cm and the ends of the
cylinders were capped with Polydimethylsiloxane (PDMS). Afterwards,
the stainless steel cages were wrapped in a sheet of polyvinyl
alcohol (PVA) and the cages were sterilized using alcohol. The
resulting devices were implanted subcutaneously in the backs of
rats, two for each rat, for periods of one to five weeks. At the
end of the study, animals were sacrificed and the devices were
removed. Gross pathological examination of the explanted devices
showed that there was about 1 mm thick fibrotic capsule formation
around the device. Further examination indicated that the inside of
the cage was cell and tissue free. As further described below, in
vitro studies done using the explanted cages surrounded by fibrotic
tissues showed that water, urea, sodium chloride and potassium
chloride were all capable of diffusion through the fibrotic
capsules and the cage walls.
[0116] As such, the fibrosis cage can be applied to a use of
removing waste components, including urea and ions, from a fluid
including extracellular fluid. Once waste components and/or fluid
are present in an inside space of the fibrosis cage, the waste
components can be removed by contact with a dialysis chamber, which
can be located inside the fibrosis cage, or by the fluid containing
the waste components being conveyed to a dialysis chamber at
another location. The fibrosis cage can be further applied to the
use of returning fluid without waste components or with a lowered
concentration of waste components. As such, the fibrosis cage can
be applied to the use of dialysis of the blood by lowering the
concentration of waste components in the peritoneum. Alternatively,
the fibrosis cage can be applied to the use of removing fluid from
the peritoneum. Still further, the fibrosis cage can be applied to
the use of removing fluid from the peritoneum and thereby removing
fluid from the blood and other body compartments.
[0117] During the maturation period, a fibrous tissue 6 builds over
the cage within a few weeks, leaving the inner space 5 acellular.
As illustrated in FIG. 3, in order to expedite the diffusion of
fluid in and out of the cage 1, a pump or pumping means 7 is placed
therein or at another location. The pump or pumping means 7 is not
limited to any particular type of pump. In some embodiments, the
non-limiting pump or pumping means 7 can be a bellows pump, a
peristaltic pump, a syringe pump, an impeller pump, a pulsatile
pump, or any other suitable pump known to those of ordinary skill
One non-limiting example of an impeller type pump has an impeller
rotatably positioned inside a housing wherein the impeller
generates a rotating torque to enable movement of fluid. The pump
or pumping means 7 forces fluid in and out of the cage 1
periodically via expansion and contraction or via another pumping
mechanism. As shown in FIG. 3, a diaphragm 45 can be provided as
part of the pump or pumping means 7 to assist in moving fluid in
and out of the cage 1. The pump or pumping means 7 can be driven by
an implanted rechargeable battery, or an externally supplied
magnetic field. In certain embodiments, the rechargeable battery is
rechargeable by wireless energy transfer. An optional pressure
gauge 12 can monitor the fluid pressure within the fibrosis cage
1.
[0118] In certain embodiments, a dialysis chamber 8 within the
fibrosis cage 1 is placed in front of the pump or pumping means 7
and remains in constant contact with the extracellular fluid from
the peritoneum that is flowing in and out of the cage. In certain
embodiments, due to the reduction in the concentration of waste
components in the extracellular fluid, a concentration gradient
between the blood and extracellular fluid across the peritoneal
membrane is maintained to drive the dialysis of waste components
from the blood across the peritoneal membrane 3. In other
embodiments, bulk movement of fluid volume from the blood to the
extracellular fluid, which can then be removed by the medical
device, occurs across the peritoneal membrane 3 to assist bulk
removal of fluid from a subject or patient. The dialysis chamber 8
includes a dialysis membrane across which exchange between a
dialysate solution and extracellular fluid within space 5 occurs.
The dialysate from the dialysis chamber 8 can be regenerated using
an optional dialysate cleansing unit. Alternatively, a fresh supply
of dialysate can be supplied to the dialysis chamber 8 to maintain
a concentration gradient between the dialysate and the
extracellular fluid. That is, in certain embodiments dialysis
across a dialysis membrane is performed by providing a fresh supply
of a dialysate to the dialysis chamber 8 wherein the dialysate is
not regenerated by treatment with a sorbent or a dialysate
cleansing unit.
[0119] The system shown in FIG. 3 performs dialysis by circulating
a dialysate solution through the dialysis chamber 8 via inlet port
9 and outlet port 10 of the dialysis chamber 8. During dialysis,
waste components in the extracellular fluid from the peritoneum
contained within the fibrosis cage are transported by diffusion
across the dialysis membrane of the dialysis chamber 8 to the
dialysate. Effluent dialysate exits the dialysis chamber 8 via
outlet port 10 and enters an optional external dialysate cleansing
unit 11. The optional external dialysate cleansing unit 11 contains
sorbents which are used to remove waste components such as urea and
ions from the dialysate. The structure of the external dialysate
cleansing unit 11 and sorbents is not limited provided that waste
components are removed from effluent dialysate. In some
embodiments, sorbents similar to the REDY sorbent system can be
used. Roberts M. The regenerative dialysis (REDY) sorbent system,
Nephrology 4:275-278, (1998). The dialysate cleansing unit 11 can
also be provided in the dialysis unit 30 described in FIG. 2. Waste
components include urea, potassium ions and various nitrate ions.
The sorbent packages are cartridges which can be replaced by the
patient when saturated by waste components. Once cleansed, the
dialysate exits the external dialysate cleansing unit 11 and
returns to the dialysate chamber 8 to continue dialysis. In an
alternate embodiment, a supply of fresh dialysate is supplied to
the dialysis chamber 8 and a dialysate cleansing unit is not
present. That is, the dialysate exiting outlet 10 is discarded and
replenished with fresh dialysate solution.
[0120] Referring now to FIG. 5, another embodiment of a dialysis
system according to the present invention having an electrodialysis
unit is described. The embodiment of FIG. 5 is similar to that of
FIG. 3, except the embodiment of FIG. 5 does not include an
external sorbent-based dialysate cleansing unit, and instead
includes an electrodialysis cleansing unit 13. FIG. 5 shows an
electrodialysis cleansing unit 13 located internal to the fibrosis
cage 1. In other embodiments, an electrodialysis cleansing unit 13
can also be provided in the embodiment described in FIG. 2 either
inside the cage 1 or inside the dialysis unit 30. The embodiment of
FIG. 5 also includes an optional catheter 14 for discharge of waste
components to a patient's bladder or removed from the patient's
body and either discarded or optionally treated
[0121] In the embodiment of FIG. 5, dialysate cleansing is
accomplished by electrodialysis. The electrodialysis unit 13
generates a pseudo urine and discharges it into the bladder via a
catheter 14 or removed from the patient's body and either discarded
or optionally treated. The electrodialysis unit 13 operates by
applying direct current ("DC") electrical fields to the dialysate
in order to change the osmolarity of the solution. The
electrodialysis unit includes an adjustable voltage generator to
generate electrical fields of varying magnitudes for selective
removal of waste components.
[0122] In alternate embodiments, the electrodialysis cleansing unit
13 is located outside of the fibrosis cage and can be located
outside of the body of the patient, such as in the dialysis unit 30
as shown in FIG. 2. In such embodiments, dialysate from the outlet
port 10 of the dialysis chamber 8 is transported to an external
electrodialysis unit (not shown) where the dialysate is treated.
The dialysate can then either be treated by electrodialysis or the
dialysate can be partially discarded with the remainder of the
dialysate treated by electrodialysis. Then, the treated dialysate
is retuned via the inlet port 9 of the dialysis chamber 8. The
transport of dialysate from the dialysis chamber 8 to the
electrodialysis unit can be accomplished by the pump or pumping
means 7 or by an additional pumping means.
[0123] Referring to FIG. 6, the electrodialysis unit 13 of FIG. 5
is shown in greater detail. Effluent dialysate enters the
electrodialysis chamber via inlet port 10. Electrical fields
generated by a power source 15 create an electric potential which
drives movement of the ions to concentrate them in different
chambers. Hypoosmotic dialysate exits the electrodialysis unit via
outlet port 9 while a hyperosmotic dialysate solution is discharged
into the urinary bladder or removed from the patient's body and
either discarded or optionally treated via outlet port or catheter
14. The hypoosmotic dialysate returns to the dialysate chamber 8 of
FIG. 5 to continue dialysis.
[0124] By adjusting the electric potential generated by the power
source 15, the osmolarity of the solutions can be controlled,
permitting regulation of fluid and salt removal from the dialysate,
and in turn from the patient. The device can be built as a
completely implantable system, and can be powered by an internal or
external power source, or a combination of an internal and external
power source. Power sources may include implanted batteries or an
external magnetic field. A programmable controller can regulate
fluid and salt extraction and flow rates through the system.
[0125] In both of the embodiments shown by FIGS. 3 and 5, the
growth of fibrotic tissue over the dialysis chamber 8 is prevented
because the dialysis chamber is located inside the fibrosis cage.
This in turn prolongs the useful life of the dialysis chamber 8 and
provides a safe environment for dialysis to take place.
Furthermore, by physically isolating the dialysate from the body,
the risk of infection is reduced dramatically. In the event that a
pathogen was to enter the dialysis chamber 8, the pathogen would
not be able to pass through the dialysis membrane and infect the
patient.
[0126] In an additional embodiment, the implanted cage and the pump
within are used to extract fluid from the body and to direct the
extracted fluid to the urinary bladder to treat fluid overload in a
patient with heart failure or cardio-renal symptoms, as shown in
FIG. 1. This embodiment can be totally implantable within the
patient, where a drainage catheter connects the fibrosis cage to
the urinary bladder for conveyance of extracted fluid to the
urinary bladder. Optionally, the conveyance of the extracted fluid
from the fibrosis cage to the urinary bladder can be assisted
and/or controlled with an additional pump. To reduce the
calcification of the drain catheter, piezoelectric vibrators can be
placed around the catheter and periodically excited. Piezoelectric
vibrators can also be provided in association with catheter 14 and
22 as shown in FIG. 1 or 5. Operation of the device in this
embodiment can be open loop to extract a certain amount of fluid
each day, governed by the patient based on a personal feedback
mechanism such as body weight, or controlled by an electronic unit
and its optional feedback sensor such as electrical impedance
monitor indicating the body fluid level.
[0127] An alternate embodiment is shown in FIG. 7, which depicts a
completely implantable implementation of the system. The fibrosis
cage 1 with fibrotic capsule 6 is used to accumulate fluid within
the device cavity 5 and fluid from the device cavity 5 is removed
via the outlet 36. Pump 42, shown as external to the fibrosis cage
1, is used both for the generation of the negative pressure inside
the device cavity 5 and also to pump the fluid via the outlet 36.
Fluid is finally disposed into the urinary bladder 20 via the
catheter 22. The pumping action commences only when the controller
18 determines that the pressure inside the device cavity 5 is equal
of more than -25 mm Hg. Pressure sensing is done by the pressure
gauge 12. Additionally, the piezoelectric vibrators 44 are
activated by the controller 18 to reduce calcification on the inner
walls of the catheter 23. In this embodiment, all components are
implanted and power can be supplied via an external unit 47 shown
in FIG. 8. Implementation depicted in FIG. 8 shows an embodiment
where the pump 42 is located internal to the fibrosis cage where
other elements are as described in FIG. 7.
[0128] In alternate embodiments of the system shown in FIG. 7, the
catheter 22 or another means can be used to remove fluid from the
cage 1 extracorporeally. That is, the catheter 22 or equivalent
structure can pass out of the body through a port or incision such
that fluid is discarded or collected outside of the body.
[0129] Embodiments of the dialysis system preferably include an
electronic controller. The electronic controller can be used to
maintain pressure within the system by regulating the total volume
of fluid within the fibrosis cage. Additionally, the controller can
adjust the dialysis rate of the system. The electronic controller
may include a programmable control unit. A control feedback system
may be formed by electrical or wireless data links between a
control unit, pump or pump means 7 and the pressure gauge 12. A
programmable control unit 18 is shown in FIGS. 1 and 2. Systems and
methods for establishing communication between an external device
and an implanted medical device have been developed, such as those
described in U.S. Pat. No. 7,023,359, Goetz et al., the subject
matter of which is incorporated herein by reference.
[0130] The control unit can also be able to detect a fluid overload
situation within the system. In the event of fluid overload, the
control unit reduces the volume of dialysate in the system in order
to extract additional amounts of fluid from the patient. The
electronic controller regulates the flow of dialysate through the
dialysis chamber 8, and also monitors the amount of dialysate
present in the dialysis chamber. A patient's fluid status can be
measured using a variety of means, such as electrical impedance
plethysmography and arterial pressure measurements.
[0131] The efficacy of dialysis performed by embodiments of the
dialysis system is governed in part by the presence of cellular
matter within the fibrosis cage. The presence of cellular matter
within a dialysis system negatively influences diffusive mass
transfer therein. Thus it is preferable to have a system which
limits the presence of cellular matter in order to maintain the
effectiveness of dialysis performed by the system.
[0132] The medical devices and methods described herein are not
limited to the treatment of humans. Rather, the medical devices and
methods described herein can be applied to other mammals including
cats and dogs and other animals commonly kept as pets but also
including exotic pets. Notably, cats oftentimes require dialysis as
treatment for end-stage renal disease (ESRD). The terms "subject"
and "patient" as used throughout this document include humans as
well as other non-human mammals. Non-limiting examples of non-human
mammals include monkeys, rabbits, gerbils, guinea pigs, hamsters,
chinchillas, ferrets, mice, rats, pigs, horses, felines, canines,
primates, hedgehogs, rodents, polecats, fennec foxes, tame silver
foxes, red foxes, skunks, raccoons, capybaras, hedgehogs, arctic
foxes, bears, coyotes, wolves and wolf/dog hybrids.
[0133] It is known that a pressure of (-)25 mmHg lower body
negative pressure ("LBNP") is tolerated by humans. In certain
embodiments, the pump or pumping means 7 is regulated not to exceed
a maximum LBNP or pressure difference between the internal volume
of the fibrosis cage of the medical device and the peritoneal
cavity, for example, 25 mmHg. However, other non-limiting ranges
for maximum pressure difference can include 10-50, 15-25, 17-29,
12-45, 23-28, and 21-38 mmHg. In some embodiments, the maximum
pressure difference can be any one of 5, 15, 20, 25, 30, 35, 40, 45
and 50 mmHg. In further embodiments, the pump or pumping means 7 is
regulated not to exceed a maximum LBNP or pressure difference
within the medical device selected from any of 5, 10, 15, and 20
mmHg. The pumping means 7 can also be regulated to not exceed a
maximum pressure difference of any one of 5, 15, 20, 25, 30, 35,
40, 45 and 50 mmHg. Furthermore, it is also known that the active
peritoneal flow is approximately 30 mL/hr/cm-H.sub.2O or 40
mL/hr/mmHg. Therefore, flow rate through the peritoneal membrane
can be calculated as:
Flow=25 mmHg.times.40 mL hr.sup.-1 mmHg.sup.-1=1 L/hr
[0134] Since the flow must be reversed periodically to empty the
chamber, the actual flow rate would be half of 1 L/hr, or 0.5 L/hr,
yielding a maximum daily flow rate of 12 L/day.
[0135] In order to limit the pressure generated by the pump or
pumping means 7, a pressure gauge 12 is utilized. During the
generation of the positive and negative pressures that are
necessary for the pumping action, the relative pressure change is
measured and pumping is paused when the absolute value of the
pressure change exceeds 25 mmHg. FIG. 4 shows a graphical
representation of the pressure changes inside the fibrosis cage,
fluid flow in and out of the cage, and fluid volume within the
cage. As discussed above, a control unit in electrical or wireless
communication with the pump or pumping means 7 and pressure gauge
12 may be used to regulate the pressure of fluid within the
fibrosis cage.
[0136] It will be apparent to one skilled in the art that
variations of the present invention are possible. For example, the
dialysis chamber 8 can be constructed in layers, and additional
layers can be used to increase the efficacy of dialysis.
Modifications to the shape of the cage and the internal structures
such as the pump or pumping means 7 can also be incorporated to
improve the system dialysis function, anatomical fit, and cosmetic
appearance of the device.
[0137] It will also 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.
EXAMPLE
[0138] Cylinder shaped cages were formed using stainless steel and
polyester meshes. Ends of the cylinders were capped using poly
(N,N-dimethylacrylamide), also known as PDMA. A picture of the
stainless steel cage can be seen in FIG. 9. The size the cage in
FIG. 9 is shown relative to a Japanese 100 yen coin. Some of the
cages were wrapped in poly vinyl alcohol (PVA) sheets. All cages
were sterilized by dipping them in alcohol prior to
implantation.
[0139] Cages were subcutaneously implanted into rats on the back of
the animals. Animals were anesthetized with ethyl ether and small
incisions were made to place two cages in the back of each animal.
Two weeks after the implantation of the cages, the animals were
sacrificed and the cages were removed. As shown in FIGS. 10 and 11,
the cages developed fibrotic capsules during the two weeks of
implantation. FIG. 10 shows an exemplary cage formed from a
polyester mesh having a fibrotic cage. FIG. 11 shows an exemplary
cage formed from stainless steel wrapped in PVA prior to
implantation having a fibrotic cage.
[0140] Procedures were carried out in vitro to measure the
diffusion properties of the explanted device with its associated
fibrotic capsule. First, one of the PDMA caps was removed to verify
that the cages were free of tissue growth within the cage. After
verification of the absence of internal tissue growth, the cages
were partially inserted into hyperosmotic solutions to measure the
changes in the concentrations of solutes within the cavity of the
cages. Care was taken to keep the open end of the cage (having the
PDMA cap removed) above the level of the hyperosmotic solution to
prevent the solution from entering the cage by a route other than
by diffusion across the fibrotic capsule.
[0141] Two measurements were carried out to measure the diffusion
properties of the fibrotic capsule. In the first study, the cage
and the surrounding fibrotic capsule were partially immersed into a
hyperosmotic urea solution. Periodically, fluid samples were taken
from the inside of the cage to measure the urea concentration
inside the cage. The results from this study are shown in FIG. 12,
where the internal urea concentration (mM) increases as a function
of time, which indicates that urea diffuses across the fibrotic
capsule and the cage. Data for both a polyester cage and a
stainless steel cage with PVA (PVA cage) are shown in FIG. 12.
[0142] In the second study, the diffusion of potassium ions was
measured (mM) using a hyperosmotic potassium solution for a
stainless steel cage with PVA and a surrounding fibrotic capsule.
The procedure was the same as in the first study except a potassium
chloride solution was provided. As shown in FIG. 13, potassium ions
also diffuse across the fibrotic capsule and the cage.
[0143] Table 1 below shows the expected number of red blood cells
("RBC") and white blood cells ("WBC") in a patient's blood and
peritoneal cavity. The values in Table 1 reflect typical ranges
found in healthy individuals. As shown in Table 1, the cellular
concentration is substantially reduced in the peritoneal cavity
compared with the blood for all individuals regardless of
physiological or disease state. As such, placement of the device in
the peritoneal space or at a location having access to the
peritoneal space reduces exposure to blood cells. Table 2 shows an
exemplary reduction in counts of white blood cells,
polymorphonuclear neutrophils ("PMN"), macrophages ("MP"), and
lymphocytes ("LYMP") in a cage over the course of three weeks
following implantation of the cage. Marchant et al., In vivo
Biocompatibility Studies I: The Cage Implant System and a
Biodegradable Hydrogel, J. Biomed. Mat. Res. 17:301-25 (1983).
TABLE-US-00001 TABLE 1 Expected cell counts in the blood and
peritoneal cavity RBC WBC Blood 4.2-6.9 million/.mu.L
4,300-10,800/.mu.L Peritoneum <10,000/.mu.L <500/.mu.L
TABLE-US-00002 TABLE 2 Cell count (cells/.mu.L) interior to an
implanted cage with time Day Total WBC PMN MP LYMP 1 21600 20100
220 1300 3 11000 10100 170 770 4 4160 3500 110 570 5 2890 2080 84
720 7 820 390 43 390 8 730 180 60 490 11 450 42 70 340 14 260 12 14
230 17 250 4 11 240 21 120 2 14 100
* * * * *