RESUMO

Aim: The influence of variants in pharmacokinetics-related genes on long-term exposure to tacrolimus (TAC)-based therapy and clinical outcomes was investigated. Patients & methods: Brazilian kidney recipients were treated with TAC combined with everolimus (n = 178) or mycophenolate sodium (n = 97). The variants in CYP2C8, CYP2J2, CYP3A4, CYP3A5, POR, ABCB1, ABCC2, ABCG2, SLCO1B1 and SLCO2B1 were analyzed. Main results:CYP3A5*3/*3 genotype influenced increase in TAC concentration from week 1 to month 6 post-transplantation (p < 0.05). The living donor and CYP2C8*3 variant were associated with reduced risk for delayed graft function (OR = 0.07; 95% CI = 0.03-0.18 and OR = 0.45; 95% CI = 0.20-0.99, respectively, p < 0.05). Conclusion: The CYP3A5*3 variant is associated with increased early exposure to TAC. Living donor and CYP2C8*3 variant seem to be protective factors for delayed graft function in kidney recipients.

Assuntos

Citocromo P-450 CYP2C8/genética , Citocromo P-450 CYP3A/genética , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Tacrolimo/efeitos adversos , Adulto , Brasil/epidemiologia , Feminino , Genótipo , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/administração & dosagem , Imunossupressores/imunologia , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Polimorfismo de Nucleotídeo Único/genética , Tacrolimo/administração & dosagem , Tacrolimo/imunologia , Resultado do Tratamento