title: Significant increase in plasma 4β-hydroxycholesterol concentration in patients after kidney transplantation.
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.
authors.affiliation: Department of Clinical Pharmacy Faculty of Medicine, Oita University, Hasama-machi, Oita 879-5593, Japan. y-suzuki@oita-u.ac.jp
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Itoh
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sato
authors.forename: Kanako
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Yukie
authors.initials: Y
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujioka
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Sato
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohno
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Mimata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kishino
mesh_terms: D051544:Cytochrome P-450 CYP3A; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D007668:Kidney / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D020127:Recovery of Function
chemical_list: D006888:Hydroxycholesterols; C099828:cholest-5-ene-3,4-diol; D051544:Cytochrome P-450 CYP3A
keywords: CYP3A activity; end-stage renal disease; plasma; renal failure