title: Effects of CYP3A5 polymorphism and the tacrolimus 12 h concentration on tacrolimus-induced acute renal dysfunction in patients with lupus nephritis.
abstract: 1. The purpose of the present study was to investigate the effect of tacrolimus concentration in blood 12 h after administration (C12h) on acute renal dysfunction in patients with lupus nephritis (LN) taking tacrolimus once daily. 2. Five of the 35 LN patients experienced tacrolimus-induced acute renal dysfunction. 3. The average annual C12h of tacrolimus was higher for patients with events of elevated serum creatinine level than for patients not experiencing these events [6.4 (5.6-8.8) versus 2.8 (2.2-4.6) ng/mL, respectively, p=0.001]. 4. The average annual tacrolimus C12h was higher for patients with CYP3A5*3/*3 (PM) than for patients with the CYP3A5*1 allele (EM) [4.6 (3.2-6.6) versus 2.5 (2.0-3.1) ng/mL, respectively, p=0.002]. 5. The area under the receiver operating characteristic was 0.887, which gave the best sensitivity (80.0%) and specificity (86.7%) at a tacrolimus C12h (average annual C12h or C12h at events) threshold of 5.2 ng/mL. 6. C12h measurements, CYP3A5 genotyping and dose adjustments of tacrolimus should be performed to prevent acute renal dysfunction in LN patients taking tacrolimus once daily.
authors.affiliation: a Department of Pharmacy , Akita University Hospital , Akita , Japan .
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.affiliation: b Department of Hematology, Nephrology, Rheumatology , Akita University Graduate School of Medicine , Akita , Japan .
authors.forename: Atsushi
authors.initials: A
authors.lastname: Komatsuda
authors.affiliation: a Department of Pharmacy , Akita University Hospital , Akita , Japan .
authors.forename: Shotaro
authors.initials: S
authors.lastname: Kato
authors.affiliation: b Department of Hematology, Nephrology, Rheumatology , Akita University Graduate School of Medicine , Akita , Japan .
authors.forename: Masaru
authors.initials: M
authors.lastname: Togashi
authors.affiliation: c Center for Kidney Disease and Transplantation, Akita University Hospital , Akita , Japan .
authors.forename: Shin
authors.initials: S
authors.lastname: Okuyama
authors.affiliation: d Department of General Internal Medicine and Clinical Laboratory Medicine , Akita University Graduate School of Medicine , Akita , Japan , and.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Omokawa
authors.affiliation: b Department of Hematology, Nephrology, Rheumatology , Akita University Graduate School of Medicine , Akita , Japan .
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nara
authors.affiliation: e Department of Life Science , Graduate School of Engineering and Resource Science, Akita University , Akita , Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Wakui
authors.affiliation: b Department of Hematology, Nephrology, Rheumatology , Akita University Graduate School of Medicine , Akita , Japan .
authors.forename: Naoto
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: a Department of Pharmacy , Akita University Hospital , Akita , Japan .
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000139:chemically induced* / Q000150:complications; D008181:Lupus Nephritis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016559:Tacrolimus / Q000009:adverse effects* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
keywords: Acute renal dysfunction; CYP3A5 polymorphism; lupus nephritis; tacrolimus; therapeutic drug monitoring