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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