Association of , and Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients.

The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 () deletion polymorphism, was further analyzed. Polymorphisms in (rs6721961), (rs4880), (rs1050450), and were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The / genotype increased ESRD risk (OR = 2.01, = 0.002), which was even higher in combination with the genotype (OR = 3.27, = 0.019). Polymorphism in also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the (/) and / genotypes in addition to a patients' age and polymorphism. Similarly, the / genotype contributed to longer cardiovascular survival. Conclusions: Our results show that , , and polymorphisms are associated with ESRD development and can predict survival.