Abstract

Late renal dysfunction may affect long-term outcome of nonrenal transplant recipients. We hypothesized that transforming growth factor β1 (TGFβ1) might play a role in the fibrogenic mechanisms leading to renal dysfunction. The aim was to determine whether TGFβ1 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 ≥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 TGFβ1 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 TGFβ1 high-producer genotype was associated with CrCl < 80 ml/mn/1.73 m². The TGFβ1 high-producer genotype is associated with renal dysfunction in pediatric heart recipients.

Keywords: transforming growth factor beta1; gene polymorphism; renal function; heart transplantation; pediatrics

Abbreviations

CrCl

creatinine clearance

GFR

glomerular filtration rate

TGFβ1

transforming growth factor β1

TGFβ1-H

transforming growth factor β1 high producer genotype

TGFβ1-I/L

transforming growth factor β1 intermediate and low producer genotype

Article Outline

Nomenclature

Introduction

Patients and methods

Results

Population

TGFβ1 distribution

TGFβ1 and renal function

Mean CrCl

Percentage of patients with CrCl <80 ml/mn/1.73m²

CrCl at latest follow-up

Freedom from renal dysfunction: CrCl <80 ml/mn/1.73 m²

Discussion

Acknowledgements

References