Role of TGF-β1+869T>C polymorphism in renal dysfunction one year after heart transplantation

BACKGROUND: Chronic kidney disease is a major complication after heart transplantation with wide inter-individual variability. Calcineurin inhibitor nephrotoxicity, mediated by transforming growth factor-beta1 (TGF-b1), is an important contributing factor. Our objective was to evaluate the association between TGF-b1 polymorphisms and renal dysfunction 1-year after heart transplantation. METHODS: Single-center observational study that included patients who received a first heart transplant between 1990-2013. According to the 1-year eGFR decline, patients were classified as "Stable" (decrease in eGFR< 10% or eGFR> 60 ml/min/1.73m2) or "Progressors" (decrease in eGFR> 10% and eGFR< 60 ml/min/1.73m2). "Progressors" were then subdivided by the degree of eGFR decrease in "Mild progressors" (10-30%) or "Rapid progressors" (> 30%). The association between TGF-b1 +869T> C polymorphism and other risk factors with the eGFR outcome was analysed. RESULTS: A total of 355 patients (78% male; 50.7 +/- 11.8 years) were included. According to the 1-year eGFR decline, 220 patients (62%) were classified as "Stable" and 135 (38%) as "Progressors". TGF-b1 +869CC genotype was more prevalent in "Stable" vs "Progressors" group (20% vs 8%, p = 0.009). In the multivariate analysis, female sex (p 0.02) and eGFR<60 ml/min/1.73 m2 at first month post-heart transplant (p = 0.004) remained as risk factors of eGFR decline, and TGF-beta 1 + 869CC genotype (p = 0.001) and renal dysfunction pre-heart transplant (p = 0.04) as protective factors. TGFb1 + 869CC genotype was less frequently found in "Mild progressors" compared to "Rapid progressors" [p = 0.019; OR (95%CI) = 0.19 (.05-.76)]. CONCLUSIONS: The TGF-b1 +869CC genotype is associated with a lower risk of calcineurin inhibitor nephrotoxicity after heart transplant. This genetic susceptibility could enable a more personalized patient treatment. J Heart Lung Transplant 2022;41:1672- 1678 (c) 2022 International Society for Heart and Lung Transplantation. All rights reserved.