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