Influence of CYP3A5 Genetic Polymorphism on Long-Term Renal Function in Chinese Kidney Transplant Recipients Using Limited Sampling Strategy and Abbreviated Area Under the Curve for Tacrolimus Monitoring

Chi Yuen Cheung*, Koon Ming Chan, Yuen Ting Wong, Wai Leung Chak, Otto Bekers, Johannes P. van Hooff

*Corresponding author for this work

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Abstract

Introduction: Although the association between CYP3A5 gene polymorphism and tacrolimus dosing requirements was well established, the impact on how CYP3A5 genotype affects the acute rejection and long-term renal function in patients who received kidney transplants and were treated with tacrolimus remained controversial. Design: Sixty-seven Chinese patients with kidney transplants receiving de novo tacrolimus-based immunosuppressive therapy with known CYP3A5 genotype were divided into 2 groups. Those with at least 1 CYP3A5*1 allele were CYP3A5 expressers while homozygotes for the mutant allele CYP3A5*3 were nonexpressers. Instead of trough level, our center used abbreviated area under the curve for tacrolimus monitoring. Primary outcome was the long-term renal function between both groups while secondary outcomes included the weight-adjusted daily tacrolimus dose, graft survival, incidence of biopsy-proven acute rejection (BPAR), opportunistic infection, and cancer. Results: Thirty-five (52.2%) patients were CYP3A5 expressers while 32 were nonexpressers. Mean daily tacrolimus dose in the CYP3A5 expressers and nonexpressers was 0.08 (0.03) and 0.05 (0.02) mg/kg, respectively (P< .01). Starting from 1-month posttransplant, the renal function was comparable between both groups, which persisted up to 10-year. Ten patients experienced BPAR rejection and there was no significant difference in the rejection-free survival between both groups (P= .87). There was also no significant difference in the death-censored graft survival between both groups (P= .86). Finally, the incidence of opportunistic infection and posttransplant cancer was similar between them. Discussion: There was no significant difference in renal function, graft survival, and acute rejection between CYP3A5 expressers and nonexpressers.

Original languageEnglish
Article number1526924820933823
Pages (from-to)249-253
Number of pages5
JournalProgress in Transplantation
Volume30
Issue number3
DOIs
Publication statusPublished - Sep 2020

Keywords

  • kidney transplant
  • pharmacogenetics
  • tacrolimus
  • ACUTE REJECTION
  • CALCINEURIN INHIBITORS
  • DOSE REQUIREMENTS
  • PHARMACOKINETICS
  • IMPACT
  • 6986A-GREATER-THAN-G
  • PHARMACOGENETICS
  • PHARMACODYNAMICS
  • VARIANT
  • TRIAL

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