Abstract

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.

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