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Genetic Polymorphisms Affecting Tacrolimus Metabolism and the Relationship to Post-Transplant Outcomes in Kidney Transplant Recipients

BACKGROUND: Tacrolimus is a key drug in kidney transplantation with a narrow therapeutic index. However, whether tacrolimus exposure variability affects clinical outcomes and adverse reactions remains unknown. OBJECTIVE: Our study investigated the factors that influence tacrolimus exposure in kidney...

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Detalles Bibliográficos
Autores principales: Cheng, Fang, Li, Qiang, Wang, Jinglin, Hu, Min, Zeng, Fang, Wang, Zhendi, Zhang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610755/
https://www.ncbi.nlm.nih.gov/pubmed/34824543
http://dx.doi.org/10.2147/PGPM.S337947
Descripción
Sumario:BACKGROUND: Tacrolimus is a key drug in kidney transplantation with a narrow therapeutic index. However, whether tacrolimus exposure variability affects clinical outcomes and adverse reactions remains unknown. OBJECTIVE: Our study investigated the factors that influence tacrolimus exposure in kidney transplantation recipients and the relationship between tacrolimus concentration and clinical outcomes and adverse reactions. SETTINGS AND METHODS: We examined the effect of tacrolimus concentration on clinical outcomes and adverse reactions in 201 kidney transplantation recipients, and identified clinical and pharmacogenetic factors that explain tacrolimus exposure. RESULTS: The CYP3A5 genotype was clearly associated with dose-adjusted trough blood tacrolimus concentrations (C(0)/D), whereas no significant difference was observed in patients with the CYP3A4*1B, CYP3A4*22, ABCB1, ABCC2, POR*28 or PXR alleles. Clinical factors such as red blood cell count, hemoglobin, and albumin were the most useful influence factors affecting tacrolimus C(0)/D. Besides, Wuzhi capsule increased tacrolimus C(0)/D in kidney transplantation recipients. Furthermore, higher tacrolimus concentrations were associated with higher diarrhea and post-transplant diabetes mellitus (PTDM) risk but not with acute rejection and chronic allograft kidney dysfunction. CONCLUSION: Clinical factors, medication, and CYP-enzyme polymorphisms accounted for tacrolimus concentration variability in kidney transplantation recipients. Furthermore, higher tacrolimus concentrations were associated with higher diarrhea and PTDM risk.