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

Pharmacogenomics J. 2018 Apr;18(2):227-231. doi: 10.1038/tpj.2017.14. Epub 2017 Apr 18.

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.

MeSH terms

  • Adult
  • Cyclosporine / pharmacology*
  • Female
  • Genotype*
  • Graft Survival / drug effects
  • Graft Survival / genetics*
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / trends*
  • Male
  • Middle Aged
  • Registries
  • Time Factors
  • Tissue Donors
  • Treatment Outcome
  • Uromodulin / genetics*

Substances

  • Immunosuppressive Agents
  • UMOD protein, human
  • Uromodulin
  • Cyclosporine