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

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 eva...

Full description

Saved in:
Bibliographic Details
Published in:Journal of lipid research 2013-09, Vol.54 (9), p.2568-2572
Main Authors: Suzuki, Yosuke, Itoh, Hiroki, Sato, Fuminori, Kawasaki, Kanako, Sato, Yukie, Fujioka, Takashi, Sato, Yuhki, Ohno, Keiko, Mimata, Hiromitsu, Kishino, Satoshi
Format: Article
Language:English
Subjects:
CYP3A activity
Cytochrome P-450 CYP3A
end-stage renal disease
Female
Humans
Hydroxycholesterols - blood
Kidney - physiology
Kidney Failure, Chronic - blood
Kidney Failure, Chronic - enzymology
Kidney Failure, Chronic - physiopathology
Kidney Failure, Chronic - therapy
Kidney Transplantation
Male
Patient-Oriented and Epidemiological Research
plasma
Recovery of Function
renal failure
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.P040022