Abstract
The highly variable pharmacokinetics of tacrolimus can hamper the optimal management of kidney transplant patients. This variability has been attributed to the genetic polymorphism of CYP3A5 6986A>G, but the evidence is not clear. We conducted a meta-analysis of studies evaluating the effect of CYP3A5 polymorphism on kidney transplant recipients with tacrolimus plasma concentration divided by daily dose per body weight (C/D) and clinical outcomes. We searched in MEDLINE and EMBASE. We found evidence suggesting a significantly lower C/D among CYP3A5*1 allele carriers compared with carriers of the CYP3A5*3/*3 genotype at weeks 1 and 2, and months 1, 3, 6 and 12. We demonstrated that the expresser genotype might have higher risk of acute rejection and chronic nephrotoxicity. In conclusion, CYP3A5 6986A>G polymorphism can affect tacrolimus pharmacokinetics and the incidence of acute rejection and chronic nephrotoxicity on kidney transplant recipients. Patients at high risk of developing tacrolimus-related complications could be detected even before their kidney transplant.
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Rojas, L., Neumann, I., Herrero, M. et al. Effect of CYP3A5*3 on kidney transplant recipients treated with tacrolimus: a systematic review and meta-analysis of observational studies. Pharmacogenomics J 15, 38–48 (2015). https://doi.org/10.1038/tpj.2014.38
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DOI: https://doi.org/10.1038/tpj.2014.38
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