Impact of CYP3A5 genomic variances on clinical outcomes among African American kidney transplant recipients.

Abstract

Little is known about the impact of CYP3A5 polymorphisms on transplantation outcomes among African American (AA) kidney transplant recipients (KTRs). To assess this issue, clinical outcomes were compared between AA CYP3A5*1 expressers and nonexpressers. This retrospective cohort study analyzed AA KTRs. Biopsy-proven acute rejection (BPAR), delayed graft function (DGF), glomerular filtration rate (GFR), infections, and tacrolimus dosing requirements were examined in 106 immunologically high-risk AA kidney transplant patients over a 2-year follow-up period. In CYP3A5*1 expressers compared to nonexpressers, the incidence of BPAR was significantly higher in the first 6months (13% vs 0%; P=.016) compared to 24months (13% vs 7%; P=.521). Tacrolimus total daily dose at first therapeutic level was significantly higher in CYP3A5*1 expressers (12mg/day) compared to nonexpressers (8mg/day; P<.001). Compared to CYP3A5*1 nonexpressers, DGF incidence was significantly higher among CYP3A5*1 expressers (27.6% vs 6.7%; P=.006). By contrast, median GFR was significantly higher in CYP3A5*1 expressers compared to nonexpressers (54.5mL/min vs 50.0mL/min; P=.003) at 24months. The findings from this retrospective study suggest that AAs with CYP3A5*1 expression require 50% more tacrolimus and have an increased incidence of DGF and acute rejection.