Pediatric Kidney Transplantation

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1 Pediatric Kidney Transplantation Vikas Dharnidharka, MD, MPH Associate Professor Division of Pediatric Nephrology Conflict of Interest Disclosure Vikas Dharnidharka, MD, MPH Employer: University of Florida College of Medicine Consultancy Agreements: Bristol-Meyers Squibb Honoraria: Genzyme Scientific Advisor or Membership: Chimerix, Quest Diagnostics 1 2 Objectives To understand unique aspects of pediatric kidney transplantation To review the current state of pediatric kidney transplantation in the USA To discuss research priorities for upcoming future in this area 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 3 4 1

2 Unique aspects Smaller volumes per center than in adults (10-30 transplants/year per center versus /year in adult centers) Therefore, pediatricians need multicenter data to acquire any meaningful results Very different primary causes of end-stage renal disease than with adults 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) Data Sources United Network of Organ Sharing (UNOS) and Scientific Registry of Transplant Recipients (SRTR) United States Renal Data System (USRDS) North American Pediatric Kidney Transplant Cooperative Studies (NAPRTCS) Published articles 5 6 Primary Diagnosis by Age Allocation Structural lesions (congenital, urological) account for a third of ESRD in children Glomerulopathies are more common in older children About 5-10% are unknown ESRD cause Compare to adults, where diabetes and hypertension are the two leading causes of ESRD NAPRTCS 2010 annual report 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 (called Share 35) Deceased donors <35 years age are given preferentially to pediatric patients after 0 antigen mismatch, highly sensitized patients PRA > 80%, or kidney plus other organ combined transplant 7 8 2

3 DROP IN WAITING TIME JUMP IN PROPORTION OF DECEASED DONORS 9 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 Size Does Matter! For children < 10 kg Midline abdominal wall incision Intraperitoneal kidney placement External iliac vessels may be too small for vascular anastomosis; may need to use aorta and IVC Strict attention to intravascular volume at time of clamp release and immediate post-operatively Ureteral re-implantation: similar to adults Stenting of ureter: controversial Native kidney nephrectomy may be required in Blood flow steal Persistent nephrotic syndrome Children > 30 kg: surgical techniques similar to adult

4 Day 30 Maintenance Medications Percent 100 Prednisone Cyclosporine Tacrolimus Azathioprine MMF Sirolimus Transplant Year RECENT DROP IN CHRONIC STEROID USE NAPRTCS 13 NAPRTCS 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 14 Causes of Graft Failure Time to First Rejection for Index Transplants NAPRTCS, 2010 annual report (Slope identical after red line) NAPRTCS

5 Graft Survival Percent Graft Survival Living Donor ( ) Living Donor ( ) Deceased Donor ( ) Deceased Donor ( ) Both living and deceased donor graft survival have improved Yet difference in survival between living versus deceased donation persists Years From Transplant NAPRTCS 2008 Worse graft survival in adolescents, also true for living donor FSGS and Graft Survival Patient Survival LOSS OF LIVING DONOR ADVANTAGE IN FSGS Baum, KI, NAPRTCS 2010 annual report 20 5

6 Creatinine Clearance Growth Post-Transplant By Age at Transplant years 2-5 years 6-12 years >12 years HEIGHT Z SCORE Height Z Score NAPRTCS 2010 annual report Years from Transplant Infections as Complications Causes of Death

7 Immunizations PTLD Time to PTLD by era of transplant Percent with LPD 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 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! Steroid-free results Long-term survival Better growth Long-term survival rate among children requiring renal replacement therapy was 79% at 10 years and 66% at 20 years Mortality rates were 30 times as high as for children without ESRD Better GFR Sarwal et al, Transplantation, 2003 & Am J Transplant 2009 McDonald and Craig, NEJM

8 Current and Future initiatives Viral monitoring and surveillance Steroid minimization Adherence improvement in adolescents Genomic markers Tolerance 29 8