Wearable artififial kidney and bioimplantable kidney by Dr Vishnu RS

introductionintroduction
Patients with chronic kidney disease (stage 5) or end-stage renal diseasePatients with chronic kidney disease (stage 5) or end-stage renal disease
(ESRD) usually receive dialysis three times per week in a specialist renal(ESRD) usually receive dialysis three times per week in a specialist renal
unit.unit.
More frequent haemodialysis has been demonstrated to be beneficial toMore frequent haemodialysis has been demonstrated to be beneficial to
ESRD patients in terms of both survival and quality of life.ESRD patients in terms of both survival and quality of life.
Benefits for patients include less hypertension, reduced cardiovascularBenefits for patients include less hypertension, reduced cardiovascular
disease, improved patient appetite and nutrition, improved serum albumindisease, improved patient appetite and nutrition, improved serum albumin
levels, improved anaemia and a decrease in the incidence of strokelevels, improved anaemia and a decrease in the incidence of stroke

Need for manpower (nurses and technicians)
Building new dialysis facilities
Lack of funds
Patients may not be willing or may be unsuitable for dialysis at home
Executing such a task would take time

A device that can
 Used 24 x 7
 Portable
 Able to ambulate while on treatment
 Independent of water and stationery electricity sources
 Cost effective

Wearable artificial kidney (wak)Wearable artificial kidney (wak)
The wearable artificial kidney (WAK) has been the holy grail in
kidney failure for decades .

NanodialysisNanodialysis
Wearable kidney device runs on the principle of nanodialysisWearable kidney device runs on the principle of nanodialysis
This involvesThis involves miniaturisation of hemodialysis machine apparatus
Uses sorbents for continuous regeneration of dialysate. Here only 150 -300 ml
of dialysate is needed.
 Thanks to the efficiency of the nanosorbents, the sorbent system can be very
small allowing a wearable system.

Wearable artificial kidney device (WAK)Wearable artificial kidney device (WAK)
 offering continuous blood cleansing, 24 hrs/day
 avoiding concentration peaks in the blood
 better clearance than current hemodialysis
 sorbents also remove middle molecules and protein bound toxins
 optimal mobility and better life expectancy for the patient

WAK wearable dialysis conceptWAK wearable dialysis concept
Victor Gura pioneered this work ..
A dialyzer filter exchanges toxins from the blood to a dialysateA dialyzer filter exchanges toxins from the blood to a dialysate
circuitcircuit
 The dialysate is continuously purified withThe dialysate is continuously purified with nanostructurednanostructured
sorbentssorbents
It uses 150 ml dialysate and 150 g sorbents (instead of 120 LIt uses 150 ml dialysate and 150 g sorbents (instead of 120 L
dialysate)dialysate)
 Total device is small and lightweight: 2 kgTotal device is small and lightweight: 2 kg

the circuit consist of two compartments- the blood and dialysatethe circuit consist of two compartments- the blood and dialysate
compartmentscompartments

Push pull flows
Sorbent system
Additives for dialysate
Fluid collection bag

Schematics of the WAK. Blood drawn from a double lumen catheter (red) is anticoagulated with
heparin from a reservoir (white) using a commercially available, battery-operated micro pump
(ambIT, Sorenson, Salt Lake City, UT) and circulated through the blood ...
Gura V et al. CJASN 2009;4:1441-1448
©2009 by American Society of Nephrology

Sorbent systemSorbent system
The fresh dialysate enters the dialyser and then exits to a series of sorbentThe fresh dialysate enters the dialyser and then exits to a series of sorbent
canisters where it is regenerated and bicarbonate is addedcanisters where it is regenerated and bicarbonate is added
The three sorbent canisters contain urease, activated charcoal, and bothThe three sorbent canisters contain urease, activated charcoal, and both
hydroxyl zirconium oxide and zirconium phosphatehydroxyl zirconium oxide and zirconium phosphate

sorbentssorbents
The zirconium phosphate cation exchanger is loaded with H+
and Na+
during
manufacture.
Free hydrogen ions compete with ammonium for binding to zirconium
phosphate.
By raising the dialysate pH to 7.4 (and neutralizing H+
), more sites are opened
for ammonium adsorption, optimizing urea removal

sorbentssorbents
the WAK sorbents effectively remove β2M from dialysate, mainly by charcoal
 The hemodynamic characteristics of the WAK strongly favor convection.
Since β2M is considered a marker of middle molecule uremic toxins and its
removal is desirable, the present results further support the notion that the
WAK may be effective in the treatment of uremic patients

sorbentssorbents
In the early pioneering days, patients were treated for 3–4 months with these
devices, but the cartridges had to be changed three to four times daily
Improvement in sorbent technology has enabled patients to be treated for
longer interval
Novel sorbent compounds that would enable patients to use a WAK for 7 days
without changing sorbent cartridges

Power sourcePower source
Traditional hemodialysis machines run on mains electricity, with a back up
heavy battery.
 So to be portable ,WAK must have a battery that, though small and light, will
provide enough energy to power all the necessary systems for a signiﬁcant
period of time to make the WAK independent of a ﬁxed electrical outlet

dialysatedialysateStandard hemodialysis therapy requires large volumes of fresh dialysate
The volume of fresh dialysate would require a huge weight burden that
would render wear-ability impossible
 WAK uses a sorbent system which can purify and regenerate efﬂuent
dialysate, so avoiding the need for fresh dialysate.
The dialysate should be ultra-pure and free not only of bacteria but also
of toxins and pyrogens.
To provide such quality dialysate, the WAK uses sterile 0.45% saline in
the dialysate circuit and both the tubing and sorbent systems are gamma
sterilized

additivesadditives
The ﬁnal dialysate is made by adding an electrolyte solution
and bicarbonate to the dialysis using a proportionating system in dialysis
apparatus.
Similarly, WAK was designed to have two additional pumps, one for a
bicarbonate solution and a second for an electrolyte solution to be added to the
dialysate compartment

Fluid removalFluid removal
Standard hemodialysis machines allow controlled ultraﬁltration.
 WAK must have a volumetric pump to remove ﬂuid at a physiological rate to
avoid hemodynamic problems and yet maintain euvolemia

Pilot study by Gura et al.,Pilot study by Gura et al.,
 0.6 m2 high ﬂux polysulfone dialyzer
The dialysate was regenerated using three sorbents- urease, activated charcoal
and both zirconium oxide and zirconium phosphate
Connected to the device using their usual vascular access
Anticoagulated using standard loading and maintainence dose of
unfractionated heparin

The mean blood flow was kept at 60ml/min, and ultrafiltrate flow at 50ml/minThe mean blood flow was kept at 60ml/min, and ultrafiltrate flow at 50ml/min
Feasibility study done in 8 subjects for periods varying upto 8 hours a dayFeasibility study done in 8 subjects for periods varying upto 8 hours a day

All patients tolerated the procedure wellAll patients tolerated the procedure well
Urea clearance was 22.7 ml/minUrea clearance was 22.7 ml/min
Creatinine clearance was 20.7 ml/minCreatinine clearance was 20.7 ml/min
Hourly Kt/v of 0.035Hourly Kt/v of 0.035
The safety devices stopped blood and dialysis flow at the time of incidentsThe safety devices stopped blood and dialysis flow at the time of incidents

Effective and slow removal of sodium and waterEffective and slow removal of sodium and water
Amount of potassium and phosphate removed is significantAmount of potassium and phosphate removed is significant
Able to deliver 168 hrs of continuous dialysisAble to deliver 168 hrs of continuous dialysis
The catridges containing sorbents need to be removed once in 2 daysThe catridges containing sorbents need to be removed once in 2 days

It has taken 40 years to develop a true wearable artificial kidney device
prototype
Pilot study was successfully completed by Gura et al.,
Further clinical studies to substantiate the efficacy are approved by US FDA
WAK has the potential to become the standard of care for dialysis in the future

BIOARTIFICIAL RENAL TUBULE ASSIST DEVICE
H. DAVID HUMES, WILLIAM H. FISSELL pioneered the work .
 An extracorporeal bioartificial kidney consisting of a conventional
hemofilter followed in series with a renal tubule assist device (RAD) has
been developed.

.The RAD is a hemofiltration cartridge containing 109 human renal
tubule cells grown as monolayers along the inner surface of the hollow
fibers.
The fibers provide a porous scaffold that is immunoprotective.
blood is pumped through out of body using a peristaltic pump. The
blood then enters the fibers of a hemofilter, where ultrafiltrate is
formed and delivered into the fibers of the tubule downstream to the
hemofilter.
 Processed ultrafiltrate exiting the RAD discarded as “urine.” The filtered
blood enters the RAD through the extracapillary space exiting the RAD,
the processed blood travels through a pump and is delivered back to
body.

.
The tubule unit is able to maintain viability because metabolic
substrates and low-molecular weight growth delivered to the tubule
cells from the ultrafiltration unit and the blood in the extracapillary
space.
 Furthermore, immunoprotection of the cells grown is achieved because
of the impenetrability of immunoglobulins and immunologically cells
through the hollow fibers. Rejection of the cells does not occur.

Implantable Bioartificial Kidney

.
University of California-San Francisco researchers unveiled a
prototype model of the first implantable artificial kidney on
September 2, 2010.
Led by Shuvo Roy, PhD, in the UCSF Department of Bioengineering
and Therapeutic Sciences.
First Phase (already completed) – focused on developing the
technologies required to reduce the device to a size to be tested by
animals.
Second Phase (current) – doing the work needed to scale up the
device for humans.

Silicon Nanotechnology
Current hollow-fiber membranes have limitations thick porous
polymer films have non-uniform pore sizes and degrade over time
upon exposure to body fluids.
High hydraulic permeability up to 600 ml/hr/mmHg/m2no pump needed
Manufacturing compatibility. scalable for larger quantities.

‘Two Stage System:
Silicon filter
First compartment holds thousands of nano-scale filters remove
toxins from the blood (dialysis).
Bioreactor
A second compartment would hold live kidney cells that perform
the other biological actions of a real kidney.
The entire device would be implanted in the abdomen and powered
by the body’s blood pressure, without a need for external pumps or
tubes

Wearable artififial kidney and bioimplantable kidney by Dr Vishnu RS

Wearable artififial kidney and bioimplantable kidney by Dr Vishnu RS

In this document