Donor cyp3a5 gene polymorphism alone cannot predict tacrolimus intrarenal concentration in renal transplant recipients

Mengyu Zhang, Soichiro Tajima, Tomohiro Shigematsu, Rao Fu, Hiroshi Noguchi, Keizo Kaku, Akihiro Tsuchimoto, Yasuhiro Okabe, Nobuaki Egashira, Satohiro Masuda

研究成果: Contribution to journalArticle

抜粋

CYP3A5 gene polymorphism in recipients plays an important role in tacrolimus blood pharmacokinetics after renal transplantation. Even though CYP3A5 protein is expressed in renal tubular cells, little is known about the influence on the tacrolimus intrarenal exposure and hence graft outcome. The aim of our study was to investigate how the tacrolimus intrarenal concentration (Ctissue) could be predicted based on donor CYP3A5 gene polymorphism in renal transplant recipients. A total of 52 Japanese renal transplant patients receiving tacrolimus were enrolled in this study. Seventy-four renal biopsy specimens were obtained at 3 months and 1 year after transplantation to determine the donor CYP3A5 polymorphism and measure the Ctissue by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The tacrolimus Ctissue ranged from 52 to 399 pg/mg tissue (n = 74) and was weak but significantly correlated with tacrolimus trough concentration (C0) at 3 months after transplantation (Spearman, r = 0.3560, p = 0.0096). No significant relationship was observed between the donor CYP3A5 gene polymorphism and Ctissue or Ctissue/C0. These data showed that the tacrolimus systemic level has an impact on tacrolimus renal accumulation after renal transplantation. However, donor CYP3A5 gene polymorphism alone cannot be used to predict tacrolimus intrarenal exposure. This study may be valuable for exploring tacrolimus renal metabolism and toxicology mechanism in renal transplant recipients.

元の言語英語
記事番号2976
ジャーナルInternational journal of molecular sciences
21
発行部数8
DOI
出版物ステータス出版済み - 4 2 2020

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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