Impact of TGFbeta1 gene polymorphisms on late renal function in pediatric heart transplantation.

Late renal dysfunction may affect long-term outcome of nonrenal transplant recipients. We hypothesized that transforming growth factor beta1 (TGFbeta1) might play a role in the fibrogenic mechanisms leading to renal dysfunction. The aim was to determine whether TGFbeta1 gene polymorphisms are associated with renal outcome in pediatric heart recipients. Eighty-eight patients underwent a first heart transplantation at the age of 7.1 +/- 6.5 years, received tacrolimus-based immunosuppression, and were followed for > or =1 year (6.7 +/- 3.2 years). Creatinine clearance (CrCl; ml/mn/1.73 m2) was calculated (Schwartz) before transplant, then at 1 month, 6 months, and 1 year, and yearly up to 7 years. Impaired function was defined as CrCl <80 ml/mn/1.73 m2. Mean CrCl decreased from 120 +/- 53 ml/mn/1.73 m2 before transplant to 98 +/- 40, 96 +/- 37, 102 +/- 30, and 101 +/- 38 ml/mn/1.73 m2 at, respectively, 6 months and 1, 5 (n = 58), and 7 years (n = 33). The TGFbeta1 high-producer genotype had worse CrCl than intermediate and low producers at every time point, despite similar pretransplant CrCl (pretransplant = 120 +/- 53 vs 118 +/- 55 ml/mn/1.73 m2 [p = 0.8], 1 year = 92 +/- 38 vs 113 +/- 30 ml/mn/1.73 m2 [p = 0.03]) and similar tacrolimus levels. The TGFbeta1 high-producer genotype was associated with CrCl < 80 ml/mn/1.73 m2. The TGFbeta1 high-producer genotype is associated with renal dysfunction in pediatric heart recipients.