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Nephrology Updates
Bioartificial Kidney
Dr. Chaudhary Muhammad Junaid Nazar
MBBS,MPH,FRSPH,MD INTERNAL MEDICINE,MSC NEPHROLOGY, FCPS-1
NEPHROLOGY
Senior Medical Officer,
Neohrology Department ,
Shifa International Hospital, Islamabad,Pakistan
Unmet Medical Needs
• Acute Renal Failure
1.Mortality rate exceeds 50%
• End Stage Renal Disease
1.20% Annual Mortality Rate
2.Self Withdrawal from dialysis
• Renal Transplantation Improves Survival
What Next?
History of the Artificial 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.
• Received $3 million in funding
as of October 1, 2012.
• Plan to go through human
clinical trials by 2017.
Current State
• Two Stage System:
• First compartment holds
thousands of nano-scale filters
remove toxins from the blood
(dialysis).
• 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.
Component of BAK
• Membrane Hemofilter
• Used silcon nanotechnology to produce highly
efficient and compact membrane relies on
blood pressure to perform filtration without
needing a pump or power supply
• Must be capable of producing meaningful
ultrafiltration volume at driving pressure similar
to capillary perfusion pressure while remaining
free of fouling for months
• Protein Loss must be minimal
• Bioreactor
• Field of tissue engineering to grow and maintain
renal tubule cells.
• Must be capable
1. High Volume Salt and Water reabsorption from
ultra filtrate
2. Maintain biological activity such as
autoregulation of blood pressure and
production of vitamin D
What it Plans to Solve
• Plans to replace dialysis (blood
is pumped through an external
circuit for filtration; typically
three sessions per week, 3-5
hours per session.)
• U.S. Medicare system spends
upwards of $29 billion per
year (6 percent of its total
budget) to treat kidney failure.
• $24 billion each year to pay for
dialysis.
• Allows the patient to live a
more normal lifestyle; takes
less of a toll on them than
normal from today’s dialysis.
• Maintain water and salt
balances, produce Vitamin D,
and regulate blood pressure.
Fundamental Barrier to Miniature
Key Target Specification
Completed Wafer
2nd
Generation Membrane
Anti-Biofouling Coatings
• Evaluations of 3 coatings for protein
resistance
1.Polyethylene glycol(PEG) is widely used
2.Poly(N-vinyldextran aldonamide-co-N-
vinylhexanamide
3.Polysulobetaine Methacrylate
Benchtop Testing-10 day
Clinical Trails on Dog
Plasma Analysis
Scale Up Mini hemofilter
Cell Growth
• Human renal tubule cells(HRTCs)
1. reliable isolation and expansion protocols
2.1gm od biopsy tissue for 17 doubling
Successful cryopreservation and functional
longevity
4 plus month in liquid nitrogen
6 plus month cell viability in perfusion circuit
Perfusion Flow Bioreactor
Long Term Barrier Function
Current Limitations
• Is not available for personal use (as of right
now).
• Because it is not available for humans,
transplants and dialysis are the only ways to
effectively treat kidney failure.
• Will be costly when first coming out (~$25,000
from $75,000).
Future of the Artificial Kidney
• Will go through clinical trials and be on the
market.
• Will be more affordable.
• Remove need for constant dialysis.
• Will be able to function without rejection or
malfunction.
Thank You
Bibliography
• Bole, Kristen. "UCSF Unveils Model for Implantable Artificial Kidney to Replace Dialysis." UCSF Unveils Model for
Implantable Artificial Kidney to Replace Dialysis. University of California-San Francisco, 2 Sept. 2010. Web. 17
Oct. 2012. <http://www.ucsf.edu/news/2010/09/4450/ucsf-unveils-model-implantable-artificial- kidney-replace-dialysis>.
• Bole, Kristen. "Artificial Kidney Project at UCSF Receives $3 Million in New Funding." University of California, San
Francisco. The Regents of the University of California, 1 Oct. 2012. Web. 22 Oct. 2012.
<http://www.ucsf.edu/news/2012/10/12810/artificial-kidney-project-ucsf-receives-3-million-new-funding>.
• Boyle, Rebecca. "Researchers Announce First Implantable Artificial Kidney Prototype." Popular Science. Bonnier
Corporation, 3 Sept. 2010. Web. 17 Oct. 2012. <http://www.popsci.com/science/article/2010- 09/researchers-
announce-first-artificial-kidney-prototype>.
• OneIndiaNews. "Implantable Artificial Kidney Set to Make Dialysis History." OneIndiaNews. Greynium Information
Technologies Pvt. Ltd., 3 Sept. 2010. Web. 17 Oct. 2012.
<http://news.oneindia.in/2010/09/03/implantableartificial-kidney-set-to-make-dialysishistory.html>.
• Shadiq, Sheraz. "Scientists Work on New Artificial Kidney." QUEST. S. D. Bechtel, Jr. Foundation, 21 Sept. 2010. Web. 17
Oct. 2012. <http://science.kqed.org/quest/2010/09/21/scientists-work-to-develop-artificial kidney/>.
• UCSF. "Roy Unveils Model of Bioartificial Kidney - School of Pharmacy." UCSF School of Pharmacy. The Regents of the
University of California, 03 Sept. 2010. Web. 17 Oct. 2012. <http://pharmacy.ucsf.edu/news/2010/09/03/1/>.
• U.S. Department of Health and Human Services. "National Kidney and Urologic Diseases Information
Clearinghouse (NKUDIC)." The Kidneys and How They Work Page. National Institute of Diabetes and Digestive
and Kidney Diseases, 23 Mar. 2012. Web. 17 Oct. 2012.
<http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/>.

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Junaid

  • 1. Nephrology Updates Bioartificial Kidney Dr. Chaudhary Muhammad Junaid Nazar MBBS,MPH,FRSPH,MD INTERNAL MEDICINE,MSC NEPHROLOGY, FCPS-1 NEPHROLOGY Senior Medical Officer, Neohrology Department , Shifa International Hospital, Islamabad,Pakistan
  • 2. Unmet Medical Needs • Acute Renal Failure 1.Mortality rate exceeds 50% • End Stage Renal Disease 1.20% Annual Mortality Rate 2.Self Withdrawal from dialysis • Renal Transplantation Improves Survival
  • 4. History of the Artificial 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. • Received $3 million in funding as of October 1, 2012. • Plan to go through human clinical trials by 2017.
  • 5. Current State • Two Stage System: • First compartment holds thousands of nano-scale filters remove toxins from the blood (dialysis). • 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.
  • 6.
  • 7. Component of BAK • Membrane Hemofilter • Used silcon nanotechnology to produce highly efficient and compact membrane relies on blood pressure to perform filtration without needing a pump or power supply • Must be capable of producing meaningful ultrafiltration volume at driving pressure similar to capillary perfusion pressure while remaining free of fouling for months • Protein Loss must be minimal • Bioreactor • Field of tissue engineering to grow and maintain renal tubule cells. • Must be capable 1. High Volume Salt and Water reabsorption from ultra filtrate 2. Maintain biological activity such as autoregulation of blood pressure and production of vitamin D
  • 8. What it Plans to Solve • Plans to replace dialysis (blood is pumped through an external circuit for filtration; typically three sessions per week, 3-5 hours per session.) • U.S. Medicare system spends upwards of $29 billion per year (6 percent of its total budget) to treat kidney failure. • $24 billion each year to pay for dialysis. • Allows the patient to live a more normal lifestyle; takes less of a toll on them than normal from today’s dialysis. • Maintain water and salt balances, produce Vitamin D, and regulate blood pressure.
  • 13.
  • 14. Anti-Biofouling Coatings • Evaluations of 3 coatings for protein resistance 1.Polyethylene glycol(PEG) is widely used 2.Poly(N-vinyldextran aldonamide-co-N- vinylhexanamide 3.Polysulobetaine Methacrylate
  • 18. Scale Up Mini hemofilter
  • 19. Cell Growth • Human renal tubule cells(HRTCs) 1. reliable isolation and expansion protocols 2.1gm od biopsy tissue for 17 doubling Successful cryopreservation and functional longevity 4 plus month in liquid nitrogen 6 plus month cell viability in perfusion circuit
  • 20.
  • 22. Long Term Barrier Function
  • 23.
  • 24. Current Limitations • Is not available for personal use (as of right now). • Because it is not available for humans, transplants and dialysis are the only ways to effectively treat kidney failure. • Will be costly when first coming out (~$25,000 from $75,000).
  • 25. Future of the Artificial Kidney • Will go through clinical trials and be on the market. • Will be more affordable. • Remove need for constant dialysis. • Will be able to function without rejection or malfunction.
  • 27. Bibliography • Bole, Kristen. "UCSF Unveils Model for Implantable Artificial Kidney to Replace Dialysis." UCSF Unveils Model for Implantable Artificial Kidney to Replace Dialysis. University of California-San Francisco, 2 Sept. 2010. Web. 17 Oct. 2012. <http://www.ucsf.edu/news/2010/09/4450/ucsf-unveils-model-implantable-artificial- kidney-replace-dialysis>. • Bole, Kristen. "Artificial Kidney Project at UCSF Receives $3 Million in New Funding." University of California, San Francisco. The Regents of the University of California, 1 Oct. 2012. Web. 22 Oct. 2012. <http://www.ucsf.edu/news/2012/10/12810/artificial-kidney-project-ucsf-receives-3-million-new-funding>. • Boyle, Rebecca. "Researchers Announce First Implantable Artificial Kidney Prototype." Popular Science. Bonnier Corporation, 3 Sept. 2010. Web. 17 Oct. 2012. <http://www.popsci.com/science/article/2010- 09/researchers- announce-first-artificial-kidney-prototype>. • OneIndiaNews. "Implantable Artificial Kidney Set to Make Dialysis History." OneIndiaNews. Greynium Information Technologies Pvt. Ltd., 3 Sept. 2010. Web. 17 Oct. 2012. <http://news.oneindia.in/2010/09/03/implantableartificial-kidney-set-to-make-dialysishistory.html>. • Shadiq, Sheraz. "Scientists Work on New Artificial Kidney." QUEST. S. D. Bechtel, Jr. Foundation, 21 Sept. 2010. Web. 17 Oct. 2012. <http://science.kqed.org/quest/2010/09/21/scientists-work-to-develop-artificial kidney/>. • UCSF. "Roy Unveils Model of Bioartificial Kidney - School of Pharmacy." UCSF School of Pharmacy. The Regents of the University of California, 03 Sept. 2010. Web. 17 Oct. 2012. <http://pharmacy.ucsf.edu/news/2010/09/03/1/>. • U.S. Department of Health and Human Services. "National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC)." The Kidneys and How They Work Page. National Institute of Diabetes and Digestive and Kidney Diseases, 23 Mar. 2012. Web. 17 Oct. 2012. <http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/>.

Editor's Notes

  1. The implantable bioartificial kidney builds upon the existing extracorporeal Renal Assist Device (RAD), which is a bioartificial kidney that combines a membrane hemofilter and a bioreactor of human renal tubule cells to mimic many of the metabolic, endocrine, and immunological functions of a healthy kidney. While clinical trials confirmed that the RAD can safely treat acute renal failure in a critical care setting, adoption of the RAD for routine treatment of ESRD patients is hampered by its labor-intensive and complex operation, large size, and high marginal cost. The ultimate goal of The Kidney Project is to apply microelectromechanical systems (MEMS) and nanotechnology to miniaturize the extracorporeal RAD into a surgically implantable, self-monitoring, and self-regulating bioartificial kidney.