The application of nanotechnology, microfluidics, bioreactors with kidney cells, and miniaturized sorbent systems to regenerate dialysate makes clinical reality seem closer than ever before. Finally, stem cells hold much promise, But more far realistic. In summary, nephrology is at an exciting crossroad with the application of innovative and novel technologies to RRT that hold considerable promise for the near future. Bioartificial Kidney as an ideal form of RRT would mimic the functions of natural kidneys and be affordable to the patient

1. Artificial Kidney Transplant -
?KT
Dr KENIZ Mohammed Yassine/
Consultant Nephrology / MSc Renal Transplantation. University of Liverpool

2. Plan
 CHRONIC KIDNEY DISEASE
 Treatment
 Haemodialysis
 Renal Replacement Therapy (RRT)
 Renal Transplantation
 Alternatives
 Current work on RRT
 ???? Kidney Transplant - An Exciting crossroad
 - The Feasibility
 – Technical approach

3. Abstract
 The application of nanotechnology, microfluidics, bioreactors with kidney
cells, and miniaturized sorbent systems to regenerate dialysate makes clinical
reality seem closer than ever before.
 Finally, stem cells hold much promise, But more far realistic. In summary,
nephrology is at an exciting crossroad with the application of innovative and
novel technologies to RRT that hold considerable promise for the near future.
 ??????? Kidney as an ideal form of RRT would mimic the functions of natural
kidneys and be affordable to the patient,

4. ESKD CHRONIC KIDNEY DISEASE
All individuals with a glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3
months are classified as having chronic kidney disease, irrespective of the
presence or absence of kidney damage.
STAGES OF CHRONIC KIDNEY DISEASE
 Stage 1: kidney damage with normal or relatively high GFR (≥90
mL/min/1.73 m2).
 Stage 2: Mild reduction in GFR (60–89 mL/min/1.73 m2) with kidney
damage.
 Stage 3: Moderate reduction in GFR (30–59 mL/min/1.73 m2).
 Stage 4: Severe reduction in GFR (15–29 mL/min/1.73 m2)
 Stage 5: End stage renal disease (ESRD) (GFR <15 mL/min/1.73 m2

5. History of
Haemodialysis
•The first scientific description of haemodialysis
principle was published by Graham in 1854.
•The first prototype hemodialyzer was developed
by Abel Rowntree and Tuner in 1913.
•The first hemodialyzer used on humans was
reported by Hass in 1923.
•Kolf developed the rotating drum artificial kidney
in 1945 and is succeeded in treating ARF for the
first time and it is modified in 1956
•In 1960,a plate and frame hemodialyzer called Killi
dialyzer was developed by Killi.
•In 1964 ,the hollow-fiber hemodialyzers called the
capillary kidney was First proposed by Stewart,
Creny and Mahon.
Hollow-fiber type hemodialyzers are the most
widely used

6. Artificial kidneys is
Haemodialysis
 Patients with ESRD are on intermittent
Haemodialysis based on the diffusion
principle (HD).
 Artificial kidneys or Haemodialysis is an
extracorporeal renal therapies for removal of
uremic solutes and excess plasma water
from the blood of patients with kidney
failure.

7. Major obstacles in the widespread adoption of
this therapeutic approach
 The morbidity and mortality remain unacceptably high due to the clearance
provided by HD three times per week or Continuous peritoneal dialysis (PD) is
barely 15 to 20 ml / min,
 Annual patient mortality exceeding 20% in patients with chronic end-stage renal
disease (ESRD) and greater than 50% mortality in patients in the intensive care
unit with acute renal failure (ARF).
 Need for manpower (nurses and technicians)
 Building new dialysis facilities
 Patients may not be willing or may be unsuitable for dialysis at home
 Executing such a task would take time
 Long term Costing Therapy

8. Need a new multifactorial approach in
conjunction with dialysis, to correct the
shortcomings of conventional therapy alone
CONFUSION?

9. Renal transplantation
 Based on know-how, most often surgical, this medical progress was made
possible by the discoveries made in the field of immunology, drugs, medical
instrumentation, but also through the development of transport,
telecommunications and IT infrastructures.
 The practice of transplants (organ, tissues or cells) requires the use of a human,
cadaveric or living donor. But with organ shortage, many patients can wait up to
two years on average before receiving a kidney transplant. The number of grafts
can only meet about 1/3 of the demand; the waiting list elongates. Faced with
this observation, several donation conditions were exceeded.

10. Renal Transplantation as principal means of
replacement during the ESKD
Organ Trade
 Living related  Living unrelated
Sources of kidneys:
 Deceased
The graft is mainly carried out from cadaveric graft (88% of cases).
 Organ harvesting from a living person is the ideal solution. Indeed, this
alternative guarantees better results in terms of quality of the graft, survival of the
graft and of the recipient.

11. Absolute contraindications
 Presence of potentially harmful antibodies against the donor kidney
 Antibodies against the ABO blood group antigens
 Antibodies against HLA class 1 and class II antigens
 Absolute contraindications
 Recipient is sensitized:
Pregnancy, Blood transfusions, Previous failed kidney transplant
 Tissue Typing
 Inheritance of HLA antigens Panel reactive antibodies
 White cell cross match
Recipient Evaluation

12. Donor Evaluation
 Normal renal function
 Not hypertensive
 Diabetic
 No infections; HIV, HBV, HCV
 Psychiatric evaluation: psychologically sound, no coercion
 Lab: CBC, FBS,LFT, Urine analysis, MC&S, assess GFR, CXR, ECG, HLA screening,
viral screening, tuberculin skin test, IVU, renal angiogram
 Tissue Typing
 Inheritance of HLA antigens Panel reactive antibodies
 White cell cross match

13. Phases of
immunosuppression
 Induction immunosuppression:
requires use of powerful drugs that
are specific for cells that initiate &
effect allograft directed immune
response
Antibodies ALG, ATGAM, OKT3, IL-2
receptor Abs
 Maintenance immunosuppression:
steroids, CNI, adjunctive agents
AZT, MMF
 Treatment of acute rejection: Abs,
pulsed methyl prednisolone

14. Longer Life with a Transplant
 Patients who receive a kidney transplant
typically live longer than those who stay on
dialysis.
 A living donor kidney functions, on average,
12 to 20 years, and a deceased donor
kidney from 8 to 12 years.
 Patients who get a kidney transplant before
dialysis live an average of 10 to 15 years
longer than if they stayed on dialysis.
 Younger adults benefit the most from a
kidney transplant, but even adults as old as
75 gain an average of four more years after
a transplant than if they had stayed on
dialysis.
Data from US Renal Data System. USRD 2003 annual data

15. CONCLUSION from the CONFUSION
 Even though kidney transplant is a major surgery with a phased
recovery period, it can, in comparison to dialysis, offer the opportunity
for a longer and more satisfying life.
SOLUTIONS?

16. Physicians tried after encountering a few points of failure
encountered in kidney transplantation to bypass it.
 Acute rejection appears within the first 3 posttransplant months and affects 30% of
cadaveric transplants and 27% of transplants from living donors.
 Approximately 20% of patients with transplants experience recurrent rejection episodes.

17. SO WHAT’S THE ALTERNATIVE?
 2. THE CYBORG KIDNEY.
 3. THE DARK HORSE KIDNEY.
 1. KIDNEY-ON-A-BELT.

18. 1. Kidney-on-a-Belt
 Wearable Artificial Kidney(WAK)
 On the WAK belt, which weighs 5 kilograms.
 Small two-channel pump propels the patient’s blood
and The dialysate through separate tubes into a small
dialyzer, where the standard filtering process occurs.
 WAK can improve quality of life for dialysis patients.
 Patients can walk around during treatment, eat and
drink whatever they want, and sleep.
Pilot study was completed by Gura et al.,

19. How does it
work?
 Nanodialysis
Wearable kidney device runs on the principle of nano dialysis
This involves miniaturisation of Haemodialysis machine apparatus
Uses sorbents for continuous regeneration of dialysate. Here only
150 -300 ml of dialysate is needed.
Thanks to the efficiency of the nano-sorbents, the sorbent system
can be very small allowing a wearable system.

20.  offering continuous blood cleansing, 24 hrs/day
 avoiding concentration peaks in the blood
 better clearance than current Haemodialysis
 sorbents also remove middle molecules and protein bound toxins
 optimal mobility and better life expectancy for the patient
 A dialyzer filter exchanges toxins from the blood to a dialysate circuit
 The dialysate is continuously purified with nanostructured sorbents
 It uses 150 ml dialysate and 150 g sorbents (instead off 120 L dialysate)
 Total device is small and lightweight:: 2 kg

21. Sorbent system
 The fresh dialysate enters the dialyser and then exits to a series of sorbent canisters
where is regenerated and bicarbonate is added
The three sorbent canisters contain urease, activated charcoal, and both hydroxyl
zirconium oxide and zirconium phosphate.
 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
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
 Novel sorbent compounds that would enable patients to use a WAK for 7
days………without changing sorbent cartridges.

22.  The WAK uses sterile 0.45% saline in the dialysate circuit and both the tubing
and sorbent systems are gamma sterilized.
 WAK must have a volumetric pump to remove fluid at a physiological rate to
avoid hemodynamic problems and yet maintain euvolemia
 Effective and slow removal of sodium and water
 Amount of potassium and phosphate removed is significant
 Able to deliver 168 hrs of continuous dialysis
 The cartridges containing sorbents need to be removed once in 2 days
 It has taken 40 years to develop a true wearable artificial kidney device
prototype
 Further clinical studies to substantiate the efficacy are approved by US FDA
BUT

23. Limitations of WAK
 The researchers encountered kinked tubes, an erratic pump, and batteries
and absorbent cartridges that needed replacing.
 Carbon dioxide bubbles in the dialysate circuit, and gas bubbles can be
deadly if they reach the heart or brain.
 The WAK included both gas bubble alarms and degassing vents.
 But the incidents made it clear that the device needs a redesign to reduce the
production of gas and improve its venting.
 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

24. 3. The Dark
Horse
Kidney
Currently being nurtured at IndieBio, a San Francisco accelerator for
biotech companies.
Uses a nano-filtration system to mimic the organ’s function and drains waste
products into the bladder.
Make ultrathin membranes out of crystalline silicon that would serve as the filter
between the blood and the dialysate.
A filtering unit that uses a silicon membrane with nanopores to from the blood
An innovative bioreactor unit that holds living kidney cells inside.
The bioreactor performs the various metabolic and endocrine roles of a functioning
kidney.
It’s Called also BIOARTIFICIAL RENAL TUBULE ASSIST DEVICE

25. 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.

26. Mechanism
 The RAD is a hemofiltration cartridge
containing 109 human renal tubule cells
grown as monolayers along the inner surface
of the hollow fibre.
 The fibre provide a porous scaffold that is
immunoprotective.
 blood is pumped throughout the body using
a peristaltic pump. The blood then enters the
fibre of a hemofilter, where ultrafiltrate is
formed and delivered into the fibre 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 the body.

27.  The tubule unit is able to maintain viability because
metabolic substrates and low-molecular weight growth are
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 through the hollow
fibers.
 Rejection of the cells does not occur.

28. 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.

29. Silicon
Nanotechnology
 Current hollow-fibre
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.

30. 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

31. Remember!
 Blood filtration and a cell-unfused recalibration module. While using a blood filtration
process based on silicon-membrane, instigate questioning the lifespan of that filter and the
filtration capacities after an estimated time frame post-implementation. Moreover, the urea
evacuation mechanism remains not clear and undefined.
 The way using the stem-cell techniques is long lasting and complex - as long that it’s based
on recreating a glomerular simulation requiring a biology and physiology reproducing
concept which is in his beginning and didn’t show any positive hope such as diabetes
treatment, can lead to rejection and a huge failure probability.
 Research are too complex and require more advanced stem-cell techniques wish is slow and
non-realistic process , moreover that project need more money, and funding want be easy to
get especially that this principle have been slow to pay off in other areas.
 “The bioartificial kidney, at least at first, won't provide all the functions of a "real" kidney,
such as blood pressure regulation through the renin-angiotensin system, or epo production.
It probably won't, at first, provide as "much" function as a "real" kidney - William Fissell

32. Comparison of various devices for
wearable artificial kidney

33. Project ???
Kidney
M.Keniz@liverpool.ac.uk
???? Kidney Transplant SKT - An
Exciting crossroad
??? Kidney © Copyright