Identification of factors affecting tacrolimus level and 5-year clinical outcome in kidney transplant patients

Abstract

The purpose of this study was to identify and characterize the association of various clinical variables and CYP3A5 genotypes with the pharmacokinetics of tacrolimus and outcome over 1-5 years in kidney transplantation patients in Korea. A total of 129 recipients (aged 18-65 years) administered tacrolimus were genotyped for CYP3A5 (6986A>G in intron 3; rs776746). Clinical covariates and trough levels, doses and dose-adjusted trough levels of tacrolimus, as well as complications during the 1-5 years after transplantation, were analysed. A linear mixed model was used to investigate potential factors affecting the trough levels, doses and dose-adjusted levels of tacrolimus. We identified factors affecting chronic allograft nephropathy (CAN) and tacrolimus-related complications. After adjusting for sex, body-weight and doses of corticosteroids and mycophenolate mofetil, we noted that CYP3A5 genotypes had the most profound effect on the dose and dose-adjusted trough levels of tacrolimus 1-5 years after transplantation (p < 0.001). Trough levels of tacrolimus were associated with post-transplantation hyperlipidaemia (p < 0.05), and estimated glomerular filtration rate was associated with CAN (p < 0.05). Therefore, the CYP3A5 genotype is a variable marker for tacrolimus dose requirement, and the trough level of tacrolimus should be controlled to minimize post-transplant hyperlipidaemia to achieve optimum outcome.