KIDNEY TRANSPLANTATION
Yasir A. Qazi, M.D.Associate Professor of Clinical Medicine.Medical Director, Kidney Transplantation.
Division of Nephrology.University of Southern California.
Why would Dr Smogorzewski be happy with this picture ?
IVAN KLASNIC CROATIA
• End Stage Renal Disease on the rise.
• Renal Replacement therapy– Hemodialysis.– Peritoneal Dialysis.– Kidney Transplantation.
History
First Successful Hemodialysis Machine
• Designed by Dr. Kollf in 1945
• 50 yards of sausage casing• Ford motor engine• Salt solution bath
The Herrick Brothers
First Successful Kidney Transplants
12/23/19541st Successful Renal Transplant
4/6/19621st Successful Cadaveric Renal Allograft
Why a Kidney Transplant ?Comparison to Dialysis
Kidney Transplantation is Life Prolonging Compared to Dialysis
Wolfe et al. NEJM 1999. 341:1725-30.
• Adjusted relative risk of death among recipients of a 1st cadaveric transplant
• Dialysis reference group on waitlist for a kidney transplant
• Age, race, sex, and diagnosis matched
Young Diabetics Have the Most to Gain From Kidney Transplantation
Non‐Diabetic ‐ Age Projected Yrs of Life (dialysis transplant)
Years Gained
20‐39 20 31 11
40‐59 12 19 7
60‐74 7 12 5
Diabetic ‐ Age Projected Yrs of Life (dialysis transplant)
Years Gained
20‐39 8 25 17
40‐59 8 22 14
60‐74 5 8 3
The Number of Patients Waiting for a Kidney Transplant Continues to Grow
•An increasing number of candidates are added to the waitlist
Annual Number of Kidney Transplants
20010 UNOS Data. www.unos.org
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010
All Donor Types
Deceased Donor
Living Donor
The Number of Kidney Donors Is Currently Decreasing
2009 SRTR Data. www.ustransplant.org
Total Number of Kidney Donors:2000 ‐ 2008
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
2000
2001
2002
2003
2004
2005
2006
2007
2008
All Donor Types Deceased DonorLiving Donor
•The number of cadaveric kidney donors has plateaued•The number of living kidney donors has decreased
Kidney Allocation is Wait‐Time Based (Time on Dialysis) in Our Area
Blood TypeListed in 2001
Median Wait Time(Years)
O 6.9
A 4.6
B 6.3AB 4.0
Unos Data, 2009
Kidney Transplant Waitlist by Diagnosis: 2006
Glomerular Diseases21%
Diabetes28%
Hypertensive Nephro‐sclerosis21%
Polycystic Kidneys
7%
Tubular and Interstitial Diseases
4%
Renovascular & Other Vascular Diseases
4%
Congenital, Rare Familial, & Metabolic Disorders
1%
Neoplasms0%
Other12%
Unknown2%
2009 SRTR Data. www.ustransplant.org
Indications/Contraindications
Stages of Chronic Kidney Disease
Stage GFR (mL/min/1.73 m2)1 > 902 60‐903 30‐594 15‐295 < 15 or Dialysis Transplant
Indicated
Major Contraindications to Kidney Transplantion
• Active Ischemic Heart Disease/Severe Cardiomyopathy
• Active Infection• Recent Malignancy Excluding Non‐Melanoma Skin Cancer
• Cirrhosis• Active Psychosis• Active Substance Abuse• Non‐Compliance
Immunology
Immunologic Requirements
• ABO Compatibility
• HLA CompatibilityMHC I : All Nucleated CellsMHC II: Designated Antigen Presenting Cells
Inducible Antigen Presenting Cells
• No Pre‐Formed Recipient anti‐Donor HLA Antibodies
The Major Histocompatibility Complex Includes Class I and II MHC Molecules
MHC Presents Antigens toT Cells
Endothelial Cell
T Cell
YHLA Molecule
T Cell Receptor
Self or ForeignAntigen
Interaction With Foreign MHC Leads to T Cell Activation
Endothelial CellDonor
Endothelial Cell
RecipientT Cell
YT Cell Activation
T Cell Activation Results in the Destruction of the Foreign Cell
DonorEndothelial Cell
RecipientT Cell
Y Endothelial Cell Attack
HLA Matching Occurs Along 3 Loci
Class I• HLA‐A• HLA‐B
Class II• HLA‐DR
0 to 6 Antigen Match Possible
Effect of HLA Matching on Rejection Episodes During 1st 6 Months: 1996‐2002
Handbook of Transplantation 4th Edition. Danovitch
Kidney Donors
NEW KIDNEY IN TOWN
Types of Kidney Donors
Deceased DonorBrain Dead Donation after Cardiac Death
Living Donor• Related• Unrelated
The Brain Dead (Cadaveric) Donor:Declaration of Brain Death
• Two physician exams separated by at least 2 hours.• Absence of hypothermia (<= 96 o) and/or CNS depressants.
• Coma with generalized flaccidity.• Mid‐line, fixed, and dilated pupils.• Absent corneal reflexes.• No ocular movement with head turning or cold caloric testing.
• Lack of gag, swallow, blink, or yawn.• Apnea Test: lack of spontaneous respiration when pCO2 rises above 60 mm Hg.
www.onelegacy.org
The Non‐Brain Dead (Cadaveric) Donor:Donation After Cardiac Death
1. Cessation of cardiopulmonary function for at least 5 minutes by:
EKGand
ARTERIAL PRESSURE MONITORING
2. Declaration by an attending physicianINDEPENDENT OF TRANSPLANT TEAM
Kidney Quality
SCD Kidneys
ECD Kidneys
Kidney QualityGood WorstBest
Living DonorKidneys
The Surgery
Typical Kidney Transplant Incision
• Extraperitoneal approach• Right side preferred unless
possible pancreas transplant
• Avoid cutting rectus muscle
Handbook of Transplantation 4th Edition. Danovitch
Standard Kidney Implantation
• Renal Artery to Common or External Iliac Artery
• Renal Vein to External Iliac Vein
Handbook of Transplantation 4th Edition. Danovitch
Lich‐Gregoir Ureteral Re‐Implantation
• Mucosal to mucosal apposition
• Anti‐reflux valve created using bladder muscle
• Stent routinely placed
Handbook of Transplantation 4th Edition. Danovitch
The Desired Result
Post‐op
Moderate Graft Function
Excellent Graft Function
Time
Delayed Graft Function
Creatinine Based on Graft FunctionC
reat
inin
e
Living Donor Transplantation Has the Best Outcomes
Immunosuppression
What is the similarity between a Transplant physician and a
Teenager?
BOTH ARE WORRIED ABOUT
REJECTION
The Field of Transplantation Awaited the Arrival of Cyclosporine
Pascual et al. NEJM 2002. 346:580-590.
Current Immunosuppression
Pascual et al. NEJM 2002. 346:580-590.
Catagories of Immunosuppressants
Antimetabolites Steroids Calcineurin Inhibitors
mTORInhibitors
Antibodies
•Azathioprine•Mycophenolate
•Solumedrol•Prednisone
•Cylosporine•FK506 (Prograf)
•Rapamycin•Everolimus
•OKT3•ATG•Simulect•Zenapax
Most centers use a combination of:Antibody Induction + Steroids + Calcineurin Inhibitor + Antimetabolite
Rejection Post Transplant
• HyperacutePre‐Formed Antibodies (anti‐ABO or HLA)
• Acute CellularT Cell Mediated
• Acute Humoral (Antibody)B Cell Mediated
• Chronic
Causes of Graft Injury and Loss
Causes of Graft Injury
Pascual et al. NEJM 2002. 346:580-590.
Causes of Graft Loss
Pascual et al. NEJM 2002. 346:580-590.
Is Kidney Donation Safe?
Kidney Donation Does Not Affect Life Expectancy
Ibrahim et al. NEJM 2009. 360:459-469.
Risk Factors For Reduced GFR, Albuminuria, & HTN Post-Kidney Donation
Ibrahim et al. NEJM 2009. 360:459-469.
OF ALL THE NATIONS IN THIS WORLD…. WHICH ONE IS THE BEST
?
DONATION
• 1ST SUCCESSFUL KIDNEY TRANSPLANT PERFORMED OVER 50 YEARS AGO
• ADVANCES IN IMMUNOSUPPRESSION HAVE RESULTED IN IMPROVED MEDIAN GRAFT SURVIVAL
• LIVING DONOR RENAL TRANSPLANTATION HAS A SUPERIOR OUTCOME & APPEARS SAFE FOR DONORS
• REJECTION RATES LOW BUT GOAL IS NOW SHIFTING TOWARDS…
Conclusions
TOLERANCE…
FOR THE FOLKS VIEWING THIS LECTURE REMOTELY/VIRTUALLY…
… PINK FLOYDAll you touch and all you see Is all your life will ever be…
How I wish you were here