Renal function and genetic polymorphisms in pediatric heart transplant recipients.
BACKGROUND
Common genetic variations influence rejection, infection, drug metabolism, and side effect profiles after pediatric heart transplantation. Reports in adults suggest that genetic background may influence post-transplant renal function. In this multicenter study, we investigated the association of genetic polymorphisms (GPs) in a panel of candidate genes on renal function in 453 pediatric heart transplant recipients.


METHODS
We performed genotyping for functional GPs in 19 candidate genes. Renal function was determined annually after transplantation by calculation of the estimated glomerular filtration rate (eGFR). Mixed-effects and Cox proportional hazard models were used to assess recipient characteristics and the effect of GPs on longitudinal eGFR and time to eGFR < 60 mL/min/1.73m(2).


RESULTS
Mean age at transplantation was 6.2 ± 6.1 years. Mean follow-up was 5.1 ± 2.5 years. Older age at transplant and black race were independently associated with post-transplant renal dysfunction. Univariate analyses showed FASL (C-843T) T allele (p = 0.014) and HO-1 (A326G) G allele (p = 0.0017) were associated with decreased renal function. After adjusting for age and race, these associations were attenuated (FASL, p = 0.075; HO-1, p = 0.053). We found no associations of other GPs with post-transplant renal function, including GPs in TGFβ1, CYP3A5, ABCB1, and ACE.


CONCLUSIONS
In this multicenter, large, sample of pediatric heart transplant recipients, we found no strong associations between GPs in 19 candidate genes and post-transplant renal function. Our findings contradict reported associations of CYP3A5 and TGFβ1 with renal function and suggest that genotyping for these GPs will not facilitate individualized immunosuppression for the purpose of protecting renal function after pediatric heart transplantation.
Pediatric Cardiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. brian.feingold@chp.edu
Brian
B
Feingold
Maria M
MM
Brooks
Adriana
A
Zeevi
Erin L
EL
Ohmann
Gilbert J
GJ
Burckart
Robert E
RE
Ferrell
Richard
R
Chinnock
Charles
C
Canter
Linda
L
Addonizio
Daniel
D
Bernstein
James K
JK
Kirklin
David C
DC
Naftel
Steven A
SA
Webber
D002648:Child; D002675:Child, Preschool; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007223:Infant; D007668:Kidney / Q000502:physiology*; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies