DR VISHNU R S

introductionintroductionPatients with chronic kidney disease (stage 5) or end-stage Patients with chronic kidney disease (stage 5) or end-stage

renal disease (ESRD) usually receive dialysis three times per renal disease (ESRD) usually receive dialysis three times per week in a specialist renal unit.week in a specialist renal unit.

More frequent haemodialysis has been demonstrated to be More frequent haemodialysis has been demonstrated to be beneficial to ESRD patients in terms of both survival and beneficial to ESRD patients in terms of both survival and quality of life. quality of life.

Benefits for patients include less hypertension, reduced Benefits for patients include less hypertension, reduced cardiovascular disease, improved patient appetite and cardiovascular disease, improved patient appetite and nutrition, improved serum albumin levels, improved anaemia nutrition, improved serum albumin levels, improved anaemia and a decrease in the incidence of strokeand a decrease in the incidence of stroke

Need for manpower (nurses and technicians)Building new dialysis facilitiesLack of funds Patients may not be willing or may be unsuitable for dialysis at

homeExecuting 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 .

NanodialysisNanodialysisWearable kidney device runs on the principle of nanodialysisWearable kidney device runs on the principle of nanodialysisThis involves This involves miniaturisation of hemodialysis machine apparatusUses 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 conceptVictor Gura pioneered this work .. A dialyzer filter exchanges toxins from the blood to a dialysate A dialyzer filter exchanges toxins from the blood to a dialysate

circuitcircuit The dialysate is continuously purified with The dialysate is continuously purified with nanostructured sorbentsnanostructured sorbentsIt uses 150 ml dialysate and 150 g sorbents (instead of 120 L It 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 dialysate the circuit consist of two compartments- the blood and dialysate compartmentscompartments

Push pull flows Sorbent systemAdditives for dialysateFluid 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 systemThe fresh dialysate enters the dialyser and then exits to a series of The fresh dialysate enters the dialyser and then exits to a series of

sorbent canisters where it is regenerated and bicarbonate is addedsorbent canisters where it is regenerated and bicarbonate is addedThe three sorbent canisters contain urease, activated charcoal, and The three sorbent canisters contain urease, activated charcoal, and

both hydroxyl zirconium oxide and zirconium phosphateboth hydroxyl zirconium oxide and zirconium phosphate

sorbentssorbentsThe 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

sorbentssorbentsthe 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

sorbentssorbentsIn 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 sourceTraditional 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

dialysatedialysateStandard 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

additivesadditivesThe 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 removalStandard 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 accessAnticoagulated using standard loading and maintainence dose of

unfractionated heparin

The mean blood flow was kept at 60ml/min, and ultrafiltrate flow at The mean blood flow was kept at 60ml/min, and ultrafiltrate flow at 50ml/min50ml/min

Feasibility study done in 8 subjects for periods varying upto 8 Feasibility study done in 8 subjects for periods varying upto 8 hours a dayhours a day

All patients tolerated the procedure wellAll patients tolerated the procedure wellUrea clearance was 22.7 ml/minUrea clearance was 22.7 ml/minCreatinine clearance was 20.7 ml/minCreatinine clearance was 20.7 ml/minHourly Kt/v of 0.035Hourly Kt/v of 0.035The safety devices stopped blood and dialysis flow at the time of The safety devices stopped blood and dialysis flow at the time of

incidentsincidents

Effective and slow removal of sodium and waterEffective and slow removal of sodium and waterAmount of potassium and phosphate removed is significantAmount of potassium and phosphate removed is significantAble to deliver 168 hrs of continuous dialysisAble to deliver 168 hrs of continuous dialysisThe catridges containing sorbents need to be removed once in 2 The catridges containing sorbents need to be removed once in 2

daysdays

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 FDAWAK has the potential to become the standard of care for dialysis

in the future

BIOARTIFICIAL RENAL TUBULE ASSIST DEVICEH. DAVID HUMES, WILLIAM H. FISSELL pioneered the

work . An extracorporeal bioartificial kidney consisting of a

conventionalhemofilter 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 NanotechnologyCurrent 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.

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Two Stage System: Silicon filter First compartment holds thousands of nano-scale filters

remove toxins from the blood (dialysis). BioreactorA 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

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