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BACKGROUND: Substantial evidence suggests that increased oxidative stress in hemodialysis (HD) patients may contribute to cardiovascular complications. Oxidative modifications of human serum albumin (HSA), the largest thiol pool in plasma, alter its biological properties and may affect its antioxidant potential in HD patients. METHODS: We conducted a long-term follow-up study in a cohort of normoalbuminemic HD patients to examine the impact of redox state of serum albumin on patients' survival by measuring the human nonmercaptoalbumin (HNA) fraction of HSA. RESULTS: After adjusting for potential demographic, anthropometric, and clinical confounders, a positive association of HNA level with the risk of death from cardiovascular disease (CVD) and all-cause mortality was observed in normoalbuminemic HD patients. Using stratified analysis, we found a stronger association between HNA level and the risk of death from CVD and all-cause mortality in patients with pre-existing CVD. CONCLUSIONS: Serum HNA level is a positive predictor of mortality in normoalbuminemic HD patients, especially among those with pre-existing CVD. Increased oxidative stress resulting from biological changes in serum albumin levels could contribute to accelerated atherosclerosis and the development of cardiovascular disease in HD patients.