Effect of UMOD genotype on long-term graft survival after kidney transplantation in patients treated with cyclosporine-based therapy

Abstract

The genetic rs12917707-G>T variant in uromodulin (UMOD) has been associated with renal function, chronic kidney disease and hypertension with the minor T-allele showing a protective effect. Hypertension and nephrotoxicity are adverse effects of chronic cyclosporine treatment. We tested whether UMOD rs12917707-T in donor kidneys associates with long-term graft survival in 393 Caucasian patients with stable graft function for more than 10 weeks after kidney transplantation treated with a cyclosporine-based maintenance therapy (mean graft survival 9 years). Presence of the donor T-allele had no effect on blood pressure, serum creatinine 1 year after transplantation, and on number of acute graft rejections during the first year. No significant effect on overall graft survival was observed in Kaplan-Meier analysis (P=0.65). In death-censored adjusted multivariate analysis, presence of donor T-allele associated with a significant lower hazard ratio of 0.67 (95% confidence interval: 0.46-0.97, P=0.05) for graft loss. This protective effect of the donor T-allele on graft loss observed in multivariate adjusted analysis justifies further investigations including patients treated with similar or other immunosuppressive regimens.