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

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.