Donor P - gp polymorphisms strongly influence renal function and graft loss in a cohort of renal transplant recipients with long term follow - up

Cyclosporine A (CsA) is a substrate for cytochrome P450 3A and the efflux transporter P-glycoprotein (P-gp; ABCB1), both abundantly expressed in the kidney. We retrospectively investigated the role of polymorphisms in CYP3A4, CYP3A5 and ABCB1 kidney graft donors on recipient renal function and subsequent graft loss, in a long-term cohort of recipients transplanted between 1990 and 2005. DNA from 227 donors and clinical data from the respective 259 recipients were analysed. Graft loss was significantly associated with the donor The variant haplotype was also associated with a greater decrease in renal function (homozygotes for TTT-3.047 mL.min-1 /y; heterozygotes for TTT-4.435 mL.min-1 /y; others-2.186 mL.min-1 /y; p=0.0240). ABCB1 polymorphisms in donors influence long-term graft outcome, favouring the decrease in renal function and graft loss in transplant recipients receiving CsA.