Pediatric Kidney Transplant Survival in a Predominantly Hispanic cohort

1. Pediatric Kidney Transplant Survival in a Predominantly Hispanic cohort Jayanthi Chandar, M.D. Associate Professor of Clinical Pediatrics University of Miami, Miller School of Medicine, Miami, Florida

3. Facts Incidence of kidney disease is rising in the adult population Hispanics are twice as likely to develop kidney failure compared to non-Hispanic Whites Higher prevalence of obesity and type 2 Diabetes Mellitus Number of patients with end stage kidney disease is rising by 7-8% /year The number of patients with end-stage renal disease is increasing at the rate of 7 to 8 percent per year in the United States.1 Renal transplantation is the treatment of choice for most of these patients, but the number of kidneys available for transplantation is limited.2 Since 1988, there has been a growing discrepancy between the number of transplantations performed and the number of patients awaiting transplantation, underscoring the need to maximize graft survivalThe number of patients with end-stage renal disease is increasing at the rate of 7 to 8 percent per year in the United States.1 Renal transplantation is the treatment of choice for most of these patients, but the number of kidneys available for transplantation is limited.2 Since 1988, there has been a growing discrepancy between the number of transplantations performed and the number of patients awaiting transplantation, underscoring the need to maximize graft survival

4. Facts About 14,000 kidney transplants are performed each year. Just over one third of transplanted kidneys are from living donors. At any point, about 55,000 people are on the waiting list for a kidney transplant. Every year, over 3,000 people die while waiting for a kidney transplant.

5. Racial disparities Hispanics were less likely than Whites to be placed on the waiting list for transplantation They were less likely to be transplanted Hispanics over age 50 are 25—30% more likely to have type 2 diabetes and diabetic kidney disease Hispanics are 60% less likely to donate organs

7. Renal Transplant Survival Slow deterioration of renal function over time Donor source Recipient race Calcineurin inhibitors Hypertension Infections

8. Unadjusted Graft and Patient Survival –OPTN/SRTR report Optn/srtr report…42% and 58% Centralized agency in which patients are placed on a waiting lisat for organ transplant and allocated organs depending on ABO and HLA matching and priorty. It has a collaborative to increase the number of transplantable organsOptn/srtr report…42% and 58% Centralized agency in which patients are placed on a waiting lisat for organ transplant and allocated organs depending on ABO and HLA matching and priorty. It has a collaborative to increase the number of transplantable organs

9. Unadjusted Graft and Patient Survival OPTN/SRTR report 1997-2004

10. Why do we do kidney Transplantation? Better quality of life and survival Dialysis is a life sustaining treatment Kidney transplantation achieves all of the functions of a normal kidney and eliminates the time spent on dialytic treatment Commitment to life long immunosuppressive medications

11. LD versus DD Shorter time on dialysis Pre-emptive transplants are possible Better HLA matching Eliminate cold ischemia time Help overcome organ shortage

13. UNOS Data in Children

14. Hispanic children Higher prevalence of FSGS with progression to ESKD Higher risk of obesity, diabetes (In Mexican Americans 2-5 times higher than non-hispanic Whites) and hypertension Increased prevalence and severity of Lupus Nephritis (LUMINA)

15. NAPRTCS White 60% Black 17% Hispanic 17% Other 6% 110 participating centers with 10.670 transplants North American pedaitric Trials and Collaborative registries110 participating centers with 10.670 transplants North American pedaitric Trials and Collaborative registries

16. Impetus for Study South Florida is a multi-ethnic community and Hispanics constitute 40 to 60% of the population Opportunity to study outcome measures in kidney transplantation in a pre-dominantly Hispanic community Studies on longitudinal assessment of long term renal function in children are scarce Number of hispanic patients with transplants has doubled in 10 yearsNumber of hispanic patients with transplants has doubled in 10 years

17. AIM Determine trends in kidney transplant survival and function in a multi-ethnic pediatric cohort over 2 decades

18. METHODS Chart review of children <18 years of age Years of transplant: 1985 –2005 Minimum follow up of at least 3 years of all functioning grafts Children with multi-organ transplants were excluded

19. Data collected Donor characteristics Recipient characteristics Race/ethnicity Age HLA matches Primary disease Socioeconomic status

20. Data collected Clinical characteristics Type of immune suppression Number of acute rejections Number of infections Recurrence of primary disease eGFR at 10 days, 1,3,5,7,10,15 and 20 years

21. Categorization Survival < 5 years 5-10 years >10 years Function at 1 year CKD 1 eGFR > 90ml/min/1.73m2 CKD 2 eGFR > 60 <90ml/min/1.73m2 CKD 3 eGFR <60ml/ min/1.73m2

22. Definitions Graft survival: Time period from the date of transplant to the date of graft failure resulting in renal replacement therapy, or death with a functioning graft. Acute Rejection Episode: 20% elevation in serum creatinine associated with biopsy evidence of acute rejection. Disease Recurrence: Biopsy proven disease recurrence, or massive albuminuria in the immediate post-transplant period requiring plasmapheresis.

23. Definitions Non-adherence Determined by the patient’s admittance, and undetectable or negligible calcineurin inhibitor levels (tacrolimus (TAC) levels <3 ng/ml or cyclosporine (CSA) levels < 50µg/L) or marked variations in calcineurin inhibitor levels in the weeks prior to a rejection episode.

24. Immunosuppressive regimen Anti-lymphocyte globulin or Muromonab-CD3 used for induction until 1998 Daclizumab was introduced after 1998 Anti-thymocyte globulin was given in addition to Daclizumab in 2000 Antibody to human T cells Humanized antibody to the IL2 receptor of activated TcellsAntibody to human T cells Humanized antibody to the IL2 receptor of activated Tcells

25. Immunosuppressive regimen 1985-1995 –Cyclosporine, Azathioprine and Methylprednisolone were used for maintenance therapy 1996-2005 –Tacrolimus, Mycophenolate Mofetil and Methylprednisolone were used for maintenance therapy

29. Deceased donor race 30% -Caucasian 40% African American 21% Hispanic Donor race did not impact graft survival

41. Race Typically refers to biological differences in human groups Refers to social relationships among ethnic groups shaped by historical and current patterns of discrimination

42. Ethnicity Group with a common set of traditions Traditions include language, religious practices, historical continuity, common ancestry or origin Hispanic race is heterogeneous Ethnic groups maintain a common cultural identity, but there is heterogeneity within them [89,90]. For example, Hispanics, as an ethnic group, include Hispanics of Mexican, Puerto Rican, Cuban, Spanish, South and Central American and other Spanish-speaking countries. broad range of groups with different cultures,Ethnic groups maintain a common cultural identity, but there is heterogeneity within them [89,90]. For example, Hispanics, as an ethnic group, include Hispanics of Mexican, Puerto Rican, Cuban, Spanish, South and Central American and other Spanish-speaking countries. broad range of groups with different cultures,

43. Summary Hispanic children have an intermediate advantage in kidney allograft survival compared to Caucasian and African American children There is an increased prevalence of recurrent disease and infections resulting in graft loss

44. Summary Children with renal allografts have a gradual decline in GFR. Rate of decline in GFR is greater in children with < 5 year survival GFR at the end of the first year of transplant has a major impact on subsequent graft function and survival

45. Summary Non-adherence is a major problem in children affecting graft survival. Graft survival is adversely affected by number of acute rejection episodes. Survival of LD is superior to DD

46. Future Directions Efforts to improve medication adherence in adolescent children are important. Measures to promote stabilization of long term graft function need further investigation. We need better tools to assess renal function.

47. Future Directions Prolonged graft survival will be facilitated by innovations in immunologic monitoring Development of genetic tools to define populations at risk for chronic kidney disease Pharmacogenomics to tailor immune suppression to needs of patient