Association between renal function and CYP3A5 genotype in heart transplant recipients treated with calcineurin inhibitors

Abstract

Background: The renal expression of the cytochrome P450 3A5 (CYP3A5) isoenzyme and of the adenosine triphosphate (ATP)-binding cassette (ABC) efflux transporter P-glycoprotein is inversely associated with calcineurin-induced nephrotoxicity. The aim of this study was to evaluate the association between polymorphisms of the genes encoding these proteins and the long-term renal function of heart transplant recipients treated with calcineurin inhibitors.

Methods: We performed a retrospective cohort study of 160 heart transplant recipients from two institutions who were discharged alive after transplant and who received a calcineurin inhibitor during follow-up. The aim of this study was to evaluate the impact of common variants of the genes encoding this isoenzyme (CYP3A5*1 and *3) and the transporter (ABCB1 G2677T/A and C3435T) on the renal function of these patients after heart transplantation. The primary end-point of the study was changes in the estimated glomerular filtration rate (eGFR) at hospital discharge; at 3, 6, 12, 18 and 24 months after heart transplant; and then every year for up to 9 years.

Results: After adjusting for independent predictors of eGFR during follow-up, CYP3A5 was significantly associated with eGFR after transplantation (p = 0.0002), with carriers of the CYP3A5*1 allele exhibiting a higher eGFR. None of the ABCB1 variants or haplotypes were associated with eGFR after transplantation.

Conclusion: The CYP3A5*1 genetic polymorphism is a promising marker to identify heart transplant recipients least likely to develop renal dysfunction during long-term treatment with a calcineurin inhibitor.