TT genotype of transforming growth factor beta1 +869C/T is associated with the development of chronic kidney disease after liver transplantation

Abstract

Background: Chronic kidney disease (CKD) is a frequent complication in patients with liver transplantation (LT), and calcineurin inhibitor chronic nephrotoxicity, mediated by transforming growth factor beta1 (TGF-β1) is an important contributing factor. The aim of this study was to assess the influence of genetic polymorphisms of TGF-β1 in the development of CKD at 6 months after transplantation.

Methods: One hundred sixty-four LT patients (63.4% male; overall mean age, 48.7 ± 11.6 years) were included in the analysis. CKD was considered at the 6th month after LT and was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m(2) as calculated on the basis of Modification of Diet in Renal Disease 4-variable equation. TGF-β1 +869 C/T and +915 G/C polymorphisms were analyzed with the use of hybridization with fluorescent probes and analysis by means of flow cytometry with the Luminex system. The association between the presence of CKD at 6 months and these polymorphisms, as well as with other known risk factors for CKD after LT, was considered.

Results: In the univariate analysis, the TT genotype of TGF-β1 +869 (P = .036; odds ratio, 2.1; 95% confidence interval, 1.1-4.2), age at LT (P < .001), pre-transplantation serum creatinine levels (P = .03), eGFR (P < .001), CKD (P = .027), and immunosuppression with cyclosporine (P = .017) were associated with CKD at 6 months after transplantation. In the multivariate analysis, TGF-β1 +869TT genotype (P = .017), immunosuppression with cyclosporine (P = .002), age at LT (P = .024), and pre-transplantation CKD (P < .001) remained as independent variables associated with the development of CKD at 6 months after transplantation.

Conclusions: The genetic polymorphism TGF-β1 +869 C/T may be an independent risk factor for CKD after liver transplantation.