Recovery of CYP3A Phenotype after Kidney Transplantation.

End-stage renal disease impairs drug metabolism via cytochrome P450 CYP3A; however, it is unclear whether CYP3A activity recovers after kidney transplantation. Therefore, the aim of this study was to evaluate the change in CYP3A activity measured as 4 beta-hydroxycholesterol (4 beta OHC) concentration after kidney transplantation. In total, data from 58 renal transplant recipients with 550 prospective 4 beta OHC measurements were included in the study. One sample per patient was collected before transplantation, and 2-12 samples per patient were collected 1-82 days after transplantation. The measured pretransplant 4 beta OHC concentrations ranged by >7-fold, with a median value of 22.8 ng/ml. Linear mixed-model analysis identified a 0.16-ng/ml increase in 4 beta OHC concentration per day after transplantation (P < 0.001), indicating a regain in CYP3A activity. Increasing estimated glomerular filtration rate after transplantation was associated with increasing 4 beta OHC concentration (P < 0.001), supporting that CYP3A activity increases with recovering uremia. In conclusion, this study indicates that CYP3A activity is regained subsequent to kidney transplantation.