State of Pediatric Kidney Transplantation

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State of Pediatric Kidney Transplantation

  1. 1. State of Pediatric Kidney Transplantation Vikas Dharnidharka, MD, MPH Medical Director, Pediatric Kidney Transplantation University of Florida
  2. 2. Objectives • To understand unique aspects of pediatric kidney transplantation • To review the state of pediatric kidney transplantation in the USA • To inform you about our current initiatives and research at our center
  3. 3. Common aspects in adult and pediatric kidney transplant • Transplant offers a survival advantage over the long-term and better quality of life • Work up of donor and recipient mostly the same • Allocations also through UNOS • Most surgical aspects are similar, though not all • Medications used are identical • Many complication issues are similar
  4. 4. Unique aspects • Smaller volumes per center than in adults (10-30/year versus 50-300/year) • Therefore, pediatricians need multicenter data • Very different primary causes of end-stage renal disease • Allocation issues for pediatrics • Surgical issues • Drug metabolism issues • Work up differences • Vaccinations • Graft and patient survival results • Complications and outcomes: – Growth – Infections – Post-transplant lymphoproliferative disease (PTLD)
  5. 5. Data Sources • United Network of Organ Sharing (UNOS) and Scientific Registry of Transplant Recipients (SRTR) • North American Pediatric Kidney Transplant Cooperative Studies (NAPRTCS) • Stanford University • University of Florida and Shands Transplant Center
  6. 6. Primary Diagnosis by Age FSGS GN Other Structural 100 90 80 70 Percent 60 50 40 30 20 10 0 0-1 2-5 6-12 >12 Patient Age (Years) Compare to adults, where diabetes and hypertension are the two leading causes of ESRD
  7. 7. Allocation • Pediatric recipients need to live longer with their transplant • May need multiple transplants over their lifetimes • UNOS always had preferential schemes for pediatric kidney, but prior systems did not work • October 2005: new system – Deceased donors <35 years age, relative priority to pediatric patients after 0 antigen mismatch, highly sensitized patients PRA > 80%, or kidney plus other organ combined transplant
  8. 8. Drop in waiting time
  9. 9. Jump in proportion of deceased donors
  10. 10. Surgical issues • Thrombosis rate by recipient age group – < 2 years of age 9.0% – 2-5 years: 5.5% – 6-12 years: 4.4% – > 12 years: 3.5% (P=0.01) • Thrombosis rate by donor age group – < 5 years age 8.3% – 5-10 years: 4.5% – > 10 years: 3.2% (P<0.001) • Practice changed: avoid small kidneys to small recipients; perform en bloc instead (superior results) Singh et al, Transplantation, 1997 Dharnidharka. AJT, 2006
  11. 11. Day 30 Maintenance Medications 100 Prednisone Cyclosporine Tacrolimus Azathioprine MMF Sirolimus 80 60 Percent 40 20 0 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Transplant Year Recent drop in chronic steroid use
  12. 12. Drug metabolism in pediatrics • Immunosuppressive agents are metabolized much faster in very young children • CsA may need to be given three times a day, not twice • Sirolimus may need to be given twice daily, not once a day • MMF marrow toxicity can be worse in absence of concomitant steroids Filler et al, Schachter et al
  13. 13. Causes of Graft Failure 1987-2004 Cause of Index Subsequent Total Graft Failure n=2123 n=291 n=2414 Chronic Rejection 571 (33%) 101 (35%) 811 (34%) Acute Rejection 277 (13%) 39 (13%) 316 (13%) Thrombosis 220 (10%) 36 (12%) 256 (11%) Death 199 (9%) 22 (8%) 221 (9%) Recurrence 138 ( 7%) 28 (10%) 166 ( 7%) Other 718 (34%) 65 (22%) 644 (27%) NAPRTCS, 2002
  14. 14. Time to First Rejection for Index Transplants 100 100 1987-1990 1991-1994 1995-1998 80 1999-2002 Living Donor 80 2003-2007 Percent Rejection 60 60 40 40 20 20 0 0 0 12 24 36 48 Months from Transplant Slope identical after red line
  15. 15. Time to First Rejection for Index Transplants 100 100 1987-1990 1991-1994 1995-1998 Deceased Donor 80 1999-2002 80 2003-2007 Percent Rejection 60 60 40 40 20 20 0 0 0 12 24 36 48 Months from Transplant Slope not as identical, especially for recent cohort
  16. 16. Graft Survival 100 100 90 90 80 80 Percent Graft Survival 70 70 60 60 50 50 Living Donor (1987-1995) Living Donor (1996-2007) 40 Deceased Donor (1987-1995) 40 Deceased Donor (1996-2007) 30 30 0 1 2 3 4 5 6 7 Years From Transplant
  17. 17. Worse graft survival in adolescents, also true for living donor
  18. 18. FSGS and Graft Survival Loss of living donor advantage in FSGS Baum, KI, 2001
  19. 19. Patient Survival 100 100 Percent Patient Survival 90 90 80 Living Donor (1987-1995) 80 Living Donor (1996-2007) Deceased Donor (1987-1995) Deceased Donor (1996-2007) 70 70 0 1 2 3 4 5 6 7 Years from transplant
  20. 20. Creatinine Clearance Living Donor Deceased Donor 120 120 0-1 years 0-1 years 110 2-5 years 110 2-5 years 6-12 years 6-12 years >12 years >12 years 100 100 Calculated clearence Calculated clearence 90 90 80 80 70 70 60 60 50 50 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 Years from Transplant Years from Transplant
  21. 21. Standardized Score (mean + SE) By Age at Transplant HEIGHT Z SCORE -0.5 -0.5 0-1 years 2-5 years 6-12 years -1.0 >12 years -1.0 Height Z Score -1.5 -1.5 -2.0 -2.0 -2.5 -2.5 0 1 2 3 4 5 6 Years from Transplant
  22. 22. Infections as Complications 35 30 25 20 Rejection % 15 Viral All Infection 10 5 0 1-6 Months 6-24 Months 1-6 Months 6-24 Months 1987 2000 Dharnidharka, AJT, 2004
  23. 23. Causes of Death Total Living Donor Deceased Donor Functio- Function- Function- ing ing ing N % graft N % graft N % graft All deceased patients 546 100.0 256 242 100.0 119 304 100.0 137 Cause of Death Infection,Viral 44 8.1 23 24 9.9 13 20 6.6 10 Infection,Bacterial 69 12.6 34 33 13.6 15 36 11.8 19 Infection, Not Specified 43 7.9 14 22 9.1 7 21 6.9 7 Cancer/malignancy 58 10.6 40 32 13.2 23 26 8.6 17 Cardiopulmonary 84 15.4 39 30 12.4 15 54 17.8 24 Hemorrhage 33 6.0 12 9 3.7 2 24 7.9 10 Recurrence 10 1.8 1 4 1.7 1 6 2.0 0 Dialysis-related 16 2.9 0 8 3.3 0 8 2.6 0 Complications Other 136 24.9 67 61 25.2 33 75 24.7 34 Unknown 53 9.7 26 19 7.9 10 34 11.2 16 Infections together = 28.6%, plus malignancies = 39.2% These likely represent overimmunosuppression complications
  24. 24. • Big recent increase in number of recommended vaccines • Variable response to immunizations in ESRD • Increased risk with live virus vaccines post-transplantation • Fully immunize prior to transplantation as far as possible
  25. 25. PTLD Time to LPD by Era of Transplant 20 Era of transplant 1987-1992 1993-1997 Percent with LPD 15 1998-2002 2003-2006 10 5 0 0 12 24 36 48 60 72 84 Months from transplant •PTLD rate in pediatric kidney transplantation: rose from < 1 to > 3% over the years •PTLD rate in adult kidney transplantation: stayed < 1% •Highest risk factor is EBV donor/recipient mismatch (D+/R-) •Get EBV donor and recipient serology pre-transplant!
  26. 26. Steroid-free results Better growth Better GFR Sarwal, Transplantation, 2003
  27. 27. CCTPT • Cooperative Clinical Trials in Pediatric Transplantation • NIH grant mechanism for multi-center transplant clinical trials and mechanistic studies, in children • Started in 1994 – IN01 (1994-1999): completed, presented and published – SW01 (1999-2004): completed and presented – SNS01 (2004-2009): data will be presented in 2 months • Latest: – CTOT-2: looking at post-transplant donor specific antibody production and pre-emptive rituximab – CTOT-C: just funded
  28. 28. University of Florida Pediatric Kidney Transplant Program • Continuously active since early 1970s • We are the only CCTPT participating center in Florida • We are an above-average volume center, historically 13-15 transplants/year • We offer a steroid-free protocol as standard of care • Short waiting times • Have patients from throughout the state, work with all groups

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