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Meta-analysis reveals CYP3A5 expressers require higher tacrolimus doses and show varied rejection risk across ethnic populations.
Abstract Tacrolimus is a cornerstone immunosuppressant in kidney transplantation, but its pharmacokinetics show significant interindividual variability, primarily due to CYP3A5 polymorphisms. This meta-analysis evaluated the impact of CYP3A5 expresser (*1/*1, *1/*3) versus non-expresser (*3/*3) genotypes on tacrolimus concentration-to-dose (Co/D) ratios and renal allograft rejection. Fifty-one studies were included: 24 reported Co/D ratios, 17 addressed rejection episodes, and 10 provided both. CYP3A5 expressers had significantly lower Co/D ratios at all post-transplant time points, reflecting faster metabolism and higher dose requirements. Ethnicity-stratified analysis revealed stronger effects in Asians (SMD: − 1.35 to − 1.50) than in Europeans (SMD: − 0.37 to − 1.05). Although overall rejection risk was not significantly higher in expressers (OR: 1.16, p = 0.13), a significant association was found in Asian populations (OR: 1.56, p = 0.0061). These findings support genotype-guided dosing of tacrolimus to improve clinical outcomes in kidney transplant recipients.
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Khan et al. (2025) studied this question.
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