Differences in Early Tacrolimus Exposure in Kidney Transplant Recipients With and Without CYP3A5 Genotype-Guided Tacrolimus Dosing.

CYP3A5

The enzyme encoded by CYP3A5 metabolises tacrolimus: patients who express it reach the therapeutic range more slowly when the starting dose is based on body weight alone.

This single-centre retrospective study compares early tacrolimus exposure in adult kidney transplant recipients before and after the introduction, in October 2023, of CYP3A5 genotype-guided dosing. The historical cohort was dosed by weight and had research genotypes from the institutional biorepository; the genotype-guided cohort had a clinical genotype available at transplant. Median time to therapeutic steady state fell from 16.0 days (8.0-16.0) to 6.0 days (3.0-6.0) in normal metabolisers (p = 0.01), and the proportion of subtherapeutic troughs on postoperative day 2 fell from 61.1% to 25.8% in intermediate metabolisers (p = 0.01). Poor metabolisers, by contrast, were more likely to be subtherapeutic on day 2 in the genotype-guided cohort. The dose reached at steady state did not differ between cohorts and remained below the dose specified by the genotype-guided protocol.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The most instructive finding runs counter to expectation: in poor metabolisers the genotype-guided protocol produced more early underexposure than weight-based dosing, signalling a starting dose that is too low for that group at this centre. The lesson is to recalibrate a dosing algorithm locally before applying it, all the more so as the dose actually reached at steady state stayed below the protocol dose in both arms. The before-and-after comparison spans ten years of practice: concurrent changes in immunosuppression regimens and target concentrations make it impossible to credit genotyping alone with the gain seen in normal and intermediate metabolisers.

Analysis by Dr Thibaut Benquey