title: CYP3A5 polymorphism affects the increase in CYP3A activity after living kidney transplantation in patients with end stage renal disease.
abstract: OBJECTIVE
  It has been reported that cytochrome P450 (CYP)3A activity increases significantly in patients with end stage renal disease (ESRD) after kidney transplantation, with wide interindividual variability in the degree of increase. The aim of this study was to evaluate the influence of CYP3A5 polymorphism on the increase in CYP3A activity after living kidney transplantation, by measuring the plasma concentration of 4β-hydroxycholesterol.
  
  
  METHODS
  This prospective study recruited 22 patients with ESRD who underwent a first living kidney allograft transplantation, comprising 12 patients with CYP3A5*1 allele (CYP3A5*1/*1 or *1/*3) and 10 patients without CYP3A5*1 allele (CYP3A5*3/*3).
  
  
  RESULTS
  No significant difference in estimated glomerular filtration rate over time was observed between patients with the CYP3A5*1 allele and patients without the CYP3A5*1 allele, suggesting that the degrees of recovery in renal function after living kidney transplantation were similar in the two groups. However, plasma concentrations of 4β-hydroxycholesterol on days 90 (57.1 ± 13.4 vs. 39.5 ± 10.8 ng ml(-1)) and 180 (55.0 ± 14.5 vs. 42.4 ± 12.6 ng ml(-1)) after living kidney transplantation were significantly higher in the presence of the CYP3A5*1 allele than in the absence of the CYP3A5*1 allele [P = 0.0034 (95% confidence interval of difference 6.55, 28.6) and P = 0.043 (95% confidence interval of difference 0.47, 24.8), respectively], suggesting that CYP3A activity may increase markedly associated with recovery of renal function in patients with the CYP3A5*1 allele.
  
  
  CONCLUSIONS
  These findings suggest that the presence of the CYP3A5*1 allele contributes to marked elevation of CYP3A activity associated with recovery of renal function after kidney transplantation.
authors.affiliation: Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Oita, 879-5593.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Oita, 879-5593.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujioka
authors.affiliation: Department of Urology, Faculty of Medicine, Oita University, Hasama-machi, Oita, 879-5593.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, Kiyose, Tokyo, 204-8588, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Oita, 879-5593.
authors.forename: Nanako
authors.initials: N
authors.lastname: Muraya
authors.affiliation: Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Oita, 879-5593.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Oita, 879-5593.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, Kiyose, Tokyo, 204-8588, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohno
authors.affiliation: Department of Urology, Faculty of Medicine, Oita University, Hasama-machi, Oita, 879-5593.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Mimata
authors.affiliation: Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, Kiyose, Tokyo, 204-8588, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kishino
authors.affiliation: Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Oita, 879-5593.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000328:Adult; D000368:Aged; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000235:genetics* / Q000601:surgery; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies
chemical_list: D051544:Cytochrome P-450 CYP3A
keywords: 4β-hydroxycholesterol; CYP3A activity; CYP3A5 polymorphism; kidney transplantation