Significant increase in plasma 4β-hydroxycholesterol concentration in patients after kidney transplantation

Takashi Fujioka,Hiromitsu Mimata,Yuhki Sato,Yukie Sato,Hiroki Itoh,Satoshi Kishino,Keiko Ohno,Kanako Kawasaki,Yosuke Suzuki,Fuminori Sato

doi:10.1194/jlr.p040022

Takashi Fujioka, Hiromitsu Mimata + Show 8 more

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https://doi.org/10.1194/jlr.p040022

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Abstract

Several previous studies have shown that renal failure decreases not only renal elimination but also metabolic clearance of drugs, particularly those metabolized by CYP3A. However, whether recovery of renal function results in recovery of hepatic CYP3A activity remains unknown. In this study, we evaluated the effect of renal function on CYP3A activity after kidney transplantation in patients with end-stage renal disease (ESRD) by measuring the change in CYP3A activity using plasma concentration of 4β-hydroxycholesterol as a biomarker. The study enrolled 13 patients with ESRD who underwent the first kidney allograft transplantation. Morning blood samples were collected before and 3, 7, 10, 14, 21, 30, 60, 90, 120, 150 and 180 days after kidney transplantation. Plasma concentration of 4β-hydroxycholesterol was measured using GC-MS. Compared with before kidney transplantation, creatinine clearance increased significantly from day 3 after kidney transplantation and stabilized thereafter. Plasma concentration of 4β-hydroxycholesterol was elevated significantly on days 90 and 180 after kidney transplantation. In conclusion, this study suggests the recovery of CYP3A activity with improvement in renal function after kidney transplantation in patients with ESRD.

Highlights

Several previous studies have shown that renal failure decreases renal elimination and metabolic clearance of drugs, those metabolized by CYP3A
We investigated the change in CYP3A activity over time after kidney transplantation in patients with end-stage renal disease (ESRD)
Nolin et al [30] reported that hepatic and intestinal CYP3A activities were not affected in patients with ESRD compared with healthy control subjects

Summary

Introduction

Several previous studies have shown that renal failure decreases renal elimination and metabolic clearance of drugs, those metabolized by CYP3A. Whether recovery of renal function results in recovery of hepatic CYP3A activity remains unknown. We evaluated the effect of renal function on CYP3A activity after kidney transplantation in patients with end-stage renal disease (ESRD) by measuring the change in CYP3A activity using plasma concentration of 4␤-hydroxycholesterol as a biomarker. The study enrolled 13 patients with ESRD who underwent the first kidney allograft transplantation. Plasma concentration of 4␤-hydroxycholesterol was measured using GC-MS. Plasma concentration of 4␤-hydroxycholesterol was elevated significantly on days 90 and 180 after kidney transplantation. This study suggests the recovery of CYP3A activity with improvement in renal function after kidney transplantation in patients with ESRD.—Suzuki, Y., H. Significant increase in plasma 4␤-hydroxycholesterol concentration in patients after kidney transplantation.J. Lipid Res. 2013.

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