1. Renal Transplantation
J. Andrew Dreslin
Department of Urology
Children’s Hospital Boston
19 March 2003

2. Overview 1) End Stage Renal Disease
2) History of Renal Transplantation
3) Recipient/Donor Selection
4) Operative Techniques
5) Rejection/Immunosuppression
6) Results

3. End Stage Renal Disease
250/million new cases each year
GFR < 10cc/min, Cr > 8.0
Etiology:
Structural 49% (Congenital obstruction, Renal hypoplasia/dysplasia, Reflux nephropathy)
Focal Segmental Glomerulosclerosis 12%
Systemic Immunologic Disease 5%

4. Treatment Options Dialysis (30%) Renal Transplantation (70%):
In-Center
Peritoneal
Renal Transplantation (70%):
Reduced morbidity/mortality from ESRD
More cost effective (4.5 yrs)
Return to normal life-style

5. History of Renal Transplantation
Voronoy 1st human renal allograft
Murray 1st successful renal transplant
Azathioprine
Donor/Recipient matching
Cyclosporin
National Transplant Act

6. Recipient Selection Diagnose Primary Disease
Determine Risk of Recurrence
Rule-Out Unsuitable Candidates

7. Risk of Disease Recurrence
Hi Risk
Focal Glomerulosclerosis
Hemolytic Uremic Syndrome
Lo Risk
Congenital Structural Disease
Renal Dysplasia
Alport’s Syndrome
Interstitial Nephritis
Chronic Pyelonephritis

8. Donor Selection Absence of renal disease Absence of active infection
Absence of malignancy

9. Living Donors Related / Unrelated Pre-Operative Testing
Higher success rates
Longer allograft half-life
Pre-Operative Testing
ABO compatibility, lymphocyte cross-match
Serologic screening (HIV, Hep B/C, CMV, Syphilis
Imaging (CT Angio, IVP/Aortography, MRI)
Contraindications:
mental dysfunc, renal disease, hi operative risk, transmissible disease

10. Cadaver Donors Declaration of Brain Death Age 2-60 y/o
Exclusion factors: HTN, DM, Malignancy, Infection, Renal failure
Resuscitation Goals: SBP > 90, U/O > 0.5cc/kg/hr
Allocation based on point system
Local -> Regional -> National

11. Histocompability ABO blood group Human Leukocyte Antigen (HLA)
T Lymphocyte Cross-Match

12. HLA Chromosome 6 Class I Class II A, B, C
All nucleated cells and platelets
Interact w/ CD8 T cells (Cytotoxic)
Class II
DR, DQ
APCs (B cells, monocytes, macrophage)
Interact w/ CD4 T cells (Helper)

13. HLA Compatibility Haplotype homogeneity w/ 1st deg relative
DR > B > A graft survival
Improved graft survival
2 haplotype v 1 haplotype matches
2 v 1 v 0 HLA-DR
6-Antigen (6-AG)

14. Operative Techniques
Donor Nephrectomy
Recipient Transplantation

15. Donor Nephrectomy Goals: Techniques Minimize Warm Ischemia Time
Preserve Renal Vessels
Preserve Ureteral Blood Supply
Techniques
Open
Laparoscopic
Hand-Assisted

16. Recipient Operation Extraperitoneal iliac fossa
Contralateral to keep renal pelvis/ureter medial
End-to-end Renal A to Int Iliac A
End-to-side Renal V to Ext Iliac V
Ureteroneocystostomy (Extra v Trans-Vesical)

17. Prophylactic Care Pre-operative Immunizations Prophylactic therapies
Pneumococcus, Hep B, Diptheria, Tetanus, Influenza, Varicella
Prophylactic therapies
Bactrim x 3mo (UTI, Pneumocystis)
Clotrimazole lozenge/vaginal insert x 3mo (Candida)
H2-Blocker

18. Allograft Rejection

19. Hyperacute Rejection Immediate and irreversible Humoral mediated
Preformed antibodies to donor HLA
Prevent by pre-operative lymphocyte to serum x-match

20. Acute Rejection Weeks to months following transplant
25-55% of all transplants
T lymphocyte mediated against donor HLA
Febrile, graft tenderness, declining renal func
Treatable with immunosuppressants
Dx w/ renal biopsy
mononuclear infiltrate
vasculitis

21. Chronic Rejection ? Mechanism 5-7% per year after 1st year
Gradual, progressive decline of renal func
No treatment

22. Immunosuppression Prevent / reverse acute rejection
Triple therapy to decrease dosing/toxicity
Corticosteroids (2,4) Cyclosporine (2,3) Azathioprine (2) Ig/Antibodies (1,2,3) 1. Ag
Recog 2. 3.
CD8 4.
Tissue
Injury
Proliferation
CD4
Differentiation

23. Immunosuppressive Drugs
Drug Mech Use Side Effects
Glucocorticoid Inhibit IL Induct/Maint Adrenal Insuff
Rx Acute Reject Growth inhib
Cyclosporin A/ Inhibit IL Induct/Maint Nephro toxic
Tacrolimus Neuro toxic
Azathioprine Purine analog Induct/Maint Myelosupp
Anti-Lymph Ab Bind T Cells Induction Hypersens
Rx Acute Reject Anaphylaxis

24. Graft Survival North American Pediatric Renal Transplant Cooperative Study
Living Donor Graft Cadaver Donor Graft
1 Year % %
2 Year % %
5 Year % %