Higher number of tacrolimus dose adjustments in kidney transplant recipients who are extensive and intermediate CYP3A5 metabolizers

Kevin A. Reininger, Guillaume C Onyeaghala, Teresa Anderson-Haag, David S. Schladt, Baolin Wu, Weihua Guan, Casey Dorr, Rory P. Remmel, Roslyn Mannon, Arthur J. Matas, William S Oetting, Paul A Stahler, Ajay K Israni, Pamala A. Jacobson

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Kidney transplant recipients carrying the CYP3A5*1 allele have lower tacrolimus troughs, and higher dose requirements compared to those with the CYP3A5*3/*3 genotype. However, data on the effect of CYP3A5 alleles on post-transplant tacrolimus management are lacking. The effect of CYP3A5 metabolism phenotypes on the number of tacrolimus dose adjustments and troughs in the first 6 months post-transplant was evaluated in 78 recipients (64% Caucasians). Time to first therapeutic concentration, percentage of time in therapeutic range (TTR), and estimated glomerular filtration rate (eGFR) were also evaluated. Fifty-five kidney transplant recipients were CYP3A5 poor metabolizers (PM), 17 were intermediate metabolizers (IM), and 6 were extensive metabolizers (EM). Compared to PMs, EMs/IMs had significantly more dose adjustments (6.1 vs. 8.1, p =.015). Overall, 33.82% of trough measurements resulted in a dose change. There was no difference in the number of tacrolimus trough measurements between PMs and EM/IMs. The total daily tacrolimus dose requirements were higher in EMs and IMs compared to PMs (<.001). TTR was ∼50% in the PMs and EMs/IMs groups. CYP3A5 EM/IM metabolizers have more tacrolimus dose changes and higher dose requirements which increases clinical management complexity. Larger studies are needed to assess the cost and benefits of including genotyping data to improve clinical management.

Original languageEnglish (US)
Article numbere14893
JournalClinical Transplantation
Issue number4
StatePublished - Apr 2023

Bibliographical note

Funding Information:
The authors would like to thank the investigators, and clinical research staff who participated in the creation of the DeKAF and GEN03 GWAS cohorts. These cohorts were supported by NIH/NIAID grants 5U19‐AI070119 and 5U01‐AI058013. Additional support was provided by the Hennepin Healthcare Research Institute and R01‐AI140303.

Publisher Copyright:
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


  • CYP3A5
  • clinical management
  • kidney transplants
  • tacrolimus

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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