Differences in Early Tacrolimus Exposure in Kidney Transplant Recipients With and Without CYP3A5 Genotype-Guided Tacrolimus Dosing
In brief
Genotype-guided dosing cuts tacrolimus steady-state time by ten days in normal metabolizers
In a single-center review of adult kidney transplants, patients whose tacrolimus dose was set by CYP3A5 genotype reached therapeutic steady-state in a median of six days versus sixteen days with standard weight-based dosing. The approach also lowered the proportion of sub-therapeutic troughs on postoperative day two for intermediate metabolizers. Further refinement is needed, especially for poor metabolizers.
- Journal
- Clinical and translational science (Q1)
- Published
- 1 September 2026
- Study design
- Retrospective cohort
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Amy L Pasternak, Jenna Schwartz, Brett Vanderwerff, Sebastian Zöllner, Danielle J Haakinson, Mona Doshi, et al.
- PMID
- 42748365
- DOI
- 10.1111/cts.70726
Why clinicians should know about it
- Picked for Transplantation (paper of the day, 18 September 2026): Tacrolimus exposure, CYP3A5 genotype‑guided dosing in kidney transplant
Abstract
CYP3A5 genotype is a known predictor of tacrolimus dose requirements. This single-center retrospective study evaluated the impact of CYP3A5 genotype-guided dosing, implemented at our institution in 10/2023, on early tacrolimus exposure. Patients were included if they were adult kidney transplant recipients between 7/2014 and 10/2024; patients in the weight-based cohort had research CYP3A5 genotypes in the institutional research biorepository and the genotype-guided cohort had a clinical CYP3A5 genotype available at transplant. The primary outcome was time to therapeutic steady-state (TSS) and secondary outcomes included classification of trough concentration on postoperative-day (POD) 2, tacrolimus dose at TSS, and tacrolimus intrapatient variability (IPV) at 14- and 30-day post-transplant. Outcomes were also evaluated within each CYP3A5 phenotype and a per-protocol evaluation. Outcomes were compared via Mann-Whitney U, Chi-squared, or Fischer's exact tests. The median TSS was decreased in CYP3A5 normal metabolizers (6.0 days (3.0-6.0) vs. 16.0 days (8.0-16.0); p = 0.01) and CYP3A5 intermediate metabolizers had significantly fewer subtherapeutic troughs on POD2 (25.8% vs. 61.1%; p = 0.01) in the genotype-guided cohort. CYP3A5 poor metabolizers were more likely to have a subtherapeutic trough on POD2 in the genotype-guided cohort. The time below therapeutic range in the first 14 days was significantly reduced for CYP3A5 intermediate metabolizers who received per-protocol, genotype-guided dosing. The TSS dose did not differ between the cohorts but was lower than the genotype-guided protocol dosing. CYP3A5 genotype-guided dosing reduced the likelihood of early subtherapeutic exposure in CYP3A5 normal and intermediate metabolizers. Refinement of the genotype-guided dosing strategy may help further improve early tacrolimus exposure.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.