Influence of tacrolimus initial doing strategy based on the CYP3A5 polymorphisms on quantitative interstitial fibrosis, rejection rate, and long-term graft function in kidney transplant recipients.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10636
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Akita University
• Principal Investigator: Satoh Shigeru 秋田大学, 医学部, 教授 (80187195)
• Co-Investigator(Renkei-kenkyūsha): MIURA MAASTOMO 秋田大学, 医学部, 教授 (30265194) ; SAITO MITSURU 秋田大学, 医学部, 講師 (80400505) ; KOMATSUDA ATSUSHI 秋田大学, 医学部, 准教授 (70272044) ; NIIOKA TAKENORI 秋田大学, 医学部, 講師 (20722276) ; OKUYAMA SHIN 秋田大学, 医学部, 准教授 (40543286) ; FUJIYAMA NOBUHIRO 秋田大学, 医学部, 助教 (90603275)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: タクロリムス / 遺伝子多型 / 薬物動態 / 薬理遺伝学 / 線維増生 / 画像解析 / 個別投与量設計 / 拒絶反応

Outline of Final Research Achievements

We investigated the impact of CYP3A5 pharmacogenetic differences on the development of interstitial fibrosis (IF) from 0 hours to 1 year post-transplantation in 96 living kidney recipients under the same target trough regimen of tacrolimus. The relationships among CYP3A5 polymorphisms, long-term graft function, and death-censored graft survival were also examined. The mean increase in the ratio of percent IF from 0 hours to 1 year was 1.38±0.74-fold. Trough levels of tacrolimus were lower in carriers with the CYP3A5*1 allele than in those with the CTP3A5*3/*3 genotype throughout the 1 year post-transplantation period. However, CYP3A5 genetic differences were not associated with the development of IF, any clinical events, or the long-term function and survival of grafts. The clinical impact of CYP3A5 pharmacogenetic differences may be small under the current lower target trough levels with suitable therapeutic drug monitoring in a lower immunological risk population.

Free Research Field

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