CYP3A5 polymorphism affects the increase in CYP3A activity after living kidney transplantation in patients with end stage renal disease

Abstract

Aims It has been reported that cytochrome P450 (CYP)3A activity increases significantly in patients with end stage renal disease (ESRD) after kidney transplantation, with wide interindividual variability in the degree of increase. The aim of this study was to evaluate the influence of CYP3A5 polymorphism on the increase in CYP3A activity after living kidney transplantation, by measuring the plasma concentration of 4β-hydroxycholesterol. Methods This prospective study recruited 22 patients with ESRD who underwent a first living kidney allograft transplantation, comprising 12 patients with CYP3A5∗1 allele (CYP3A5∗1/∗1 or ∗1/∗3) and 10 patients without CYP3A5∗1 allele (CYP3A5∗3/∗3). Results No significant difference in estimated glomerular filtration rate over time was observed between patients with the CYP3A5∗1 allele and patients without the CYP3A5∗1 allele, suggesting that the degrees of recovery in renal function after living kidney transplantation were similar in the two groups. However, plasma concentrations of 4β-hydroxycholesterol on days 90 (57.1 ± 13.4 vs. 39.5 ± 10.8 ng ml-1) and 180 (55.0 ± 14.5 vs. 42.4 ± 12.6 ng ml-1) after living kidney transplantation were significantly higher in the presence of the CYP3A5∗1 allele than in the absence of the CYP3A5∗1 allele [P = 0.0034 (95% confidence interval of difference 6.55, 28.6) and P = 0.043 (95% confidence interval of difference 0.47, 24.8), respectively], suggesting that CYP3A activity may increase markedly associated with recovery of renal function in patients with the CYP3A5∗1 allele. Conclusions These findings suggest that the presence of the CYP3A5∗1 allele contributes to marked elevation of CYP3A activity associated with recovery of renal function after kidney transplantation.