1. Genetic determinants of tacrolimus metabolism associated with CYP3A5 in kidney transplantation: a literature review

Авторлар

DOI:

https://doi.org/10.35805/BSK2025I001

Жүктеулер

Аңдатпа

Background. Kidney transplantation is the most effective treatment for end-stage chronic kidney disease, improving quality of life and reducing mortality compared with dialysis. The success of transplantation depends on HLA compatibility, immune sensitization, immune status and immunosuppressive therapy. Tacrolimus, a key immunosuppressant, prevents graft rejection by suppressing T-cell activity and is metabolized by CYP3A4 and CYP3A5 enzymes. CYP3A5 gene polymorphisms influence enzyme activity and tacrolimus metabolism.

Methods. The review analyzed 46 of 141 publications from PubMed, MEDLINE, Embase, Scopus, and Cochrane Library databases that met the inclusion criteria and focused on the role of CYP3A5 gene polymorphisms in tacrolimus metabolism in renal transplant patients.

Results. CYP3A5 gene polymorphisms significantly affect tacrolimus pharmacokinetics. Carriers of the *1 allele (expressers) demonstrated accelerated metabolism requiring higher doses, while patients with the *3/*3 genotype (non-expressers) exhibited slower metabolism, allowing for reduced doses but increasing the risk of toxicity, including nephrotoxicity. An analysis of 46 publications and randomized studies confirmed that CYP3A5 genotyping enables personalized tacrolimus dosing. For expressers, genotyping facilitated faster achievement of therapeutic concentrations, while for non-expressers, it reduced the risk of toxic effects. However, long-term differences in clinical outcomes between groups with and without genotyping remain statistically insignificant, emphasizing the need for larger-scale studies to validate the efficacy of this approach.

Conclusion. CYP3A5 polymorphisms play a key role in the personalization of immunosuppressive therapy. Genotyping optimizes tacrolimus dosing and reduces the risk of rejection and toxicity. Integration of pharmacogenetic testing into clinical practice may improve transplantation outcomes.

Кілт сөздер

tacrolimus, CYP3A5 gene, kidney transplantation, immunosuppression, genotyping

Әдебиеттер тізімі

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2025-03-31

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№ 1 (2025)

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