Supplementary Material for: CYP3A5 Expressor Genotype of the Transplanted Kidney Increases the Risk of Preterm Graft Loss and Acute Rejection

<b><i>Introduction:</i></b> Tacrolimus is metabolized mainly in the liver by the CYP3A enzyme family, with a particularly well-documented role of CYP3A5. CYP3A5 is also expressed in the renal tissue and is present in the transplanted kidney. To date, the association between donor <i>CYP3A5</i> polymorphisms and transplant outcome remains poorly understood. The aim of this study was to assess the effect of donor CYP3A5 expression on early and long-term transplant outcomes. <b><i>Methods:</i></b> A retrospective cohort study including 207 patients who received kidney grafts from 110 deceased donors was conducted at a single Central European Center. Tissue samples from all donors were studied for <i>CYP3A5</i> single-nucleotide polymorphism (rs776746). Death-censored graft loss within 5-year follow-up, acute rejection occurrence, and kidney function, measured using serum creatinine and MDRD eGFR, were compared between groups of patients with allografts from rs776746 carriers (CYP3A5 expressors) and noncarriers (CYP3A5 nonexpressors). <b><i>Results:</i></b> Recipients who received kidneys from CYP3A5 expressors (<i>n</i> = 24) were at significantly higher risk of death-censored graft loss within 5-year follow-up (adjusted HR, 95% CI: 6.82, 2.01–23.12; <i>p</i> = 0.002) and acute rejection within the 1st posttransplant year (adjusted OR, 95% CI: 4.62, 1.67–12.77; <i>p</i> = 0.003) than those who did not (<i>n</i> = 183). The median time to loss of function was 1.93 [IQR; 0.77–3.19] years. <b><i>Conclusions:</i></b> Donor CYP3A5 expressor status is associated with worse renal graft survival and a higher risk of acute rejection. Determination of donor <i>CYP3A5</i> genotype is a potentially useful tool that may improve kidney transplant outcomes.