Recovery of CYP3A Phenotype after Kidney Transplantation

Abstract

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-hydroxycholesterol (4OHC) concentration after kidney transplantation. In total, data from 58 renal transplant recipients with 550 prospective 4OHC 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 4OHC 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 4OHC concentration per day after transplantation ( < 0.001), indicating a regain in CYP3A activity. Increasing estimated glomerular filtration rate after transplantation was associated with increasing 4OHC concentration ( < 0.001), supporting that CYP3A activity increases with recovering uremia. In conclusion, this study indicates that CYP3A activity is regained subsequent to kidney transplantation.

Gjestad et al. reply to ‘Was 4β‐hydroxycholesterol ever going to be a useful marker of CYP3A4 activity?’ by Neuhoff and Tucker

“…In the latter, pretransplant 4βOHC levels were matched with post‐transplant tacrolimus concentrations. We recently showed that 4βOHC levels increase following kidney transplantation due to regained CYP3A4 activity , which is suppressed in end‐stage renal disease . It is therefore no surprise that pretransplant 4βOHC levels did not correlate with post‐transplant tacrolimus concentrations in the study by Vanhove et al .…”