Recipient uridine 5'-diphospho-glucuronosyltransferase UGT1A9 c.98T>C variant determines transplanted kidney filtration rate.

ABSTRACT

Mycophenolic acid preparations are commonly used in prophylaxis of kidney allograft acute rejection. The medication is metabolized by uridine diphosphate glucuronosyltransferases, mainly UGT1A9 present in liver, kidney, and intestine. The effect of UGT1A9 allelic variants on drug metabolism in healthy volunteers and transplant recipients has been previously evaluated; these studies included the UGT1A9 c.98T>C polymorphism (rs72551330, p.Met33Thr) causing methionine-to-threonine substitution in the polypeptide chain. The study objective was to evaluate the relationship between UGT1A9 c.98T>C polymorphism and kidney graft function and survival and the risk of acute allograft rejection. Kidney recipients who underwent transplantation between 2000 and 2007 at the Medical University of Warsaw were included. Clinical data originated from standard medical records, UGT1A9 c.98T>C was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. A group of 243 kidney transplant recipients was enrolled in the study. The frequency of the c.98C allele was 2.4% (12 of 486). Most of the carriers of the allelic variant (10 of 12) received cyclosporine A at transplantation. In the c.98C allele carriers, worse function of the renal allograft, manifested by a significantly lower glomerular filtration rate, was found in the first posttransplantation month and persisted at a lower level for 8 years after the procedure (for comparison of the UGT1A9 c.98 TT vs the UGT1A9 c.98 TC groups, P = .03). No association was found between the presence of the UGT1A9 c.98C allele and the risk of delayed renal graft function, acute rejection, dysfunction of the renal graft, or dialysis treatment reintroduction. Significantly lower estimated glomerular filtration rate of the renal allograft in UGT1A9 c.98C carriers did not translate into decreased allograft survival.