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End-stage renal disease (ESRD) is associated with enhanced oxidative stress and may contribute to substantial cardiovascular complications in dialysis patients. Recent studies suggested that human serum albumin (HSA), the major plasma protein, may possess a direct vasculoprotective antioxidant effect. In this study, we investigated if such protective effect is impaired in uremic milieu.Thirty-one ESRD patients on maintenance haemodialysis and 22 age-matched healthy controls were recruited. Serum albumin was purified and changes in biological properties of HSA were analysed by several biochemistry techniques, spectrophotometric measurements, ligand-binding assays and western blot analysis.We found that both dityrosine (0.25 ± 0.1 vs 0.15 ± 0.07, P < 0.001), and carbonyl (10.5 ± 1.88 nmol/mg vs 5.29 ± 1.21 nmol/mg, P < 0.001) contents were increased in the uremic HSA. Decreased thiol activity of plasma was also noted and may be related to dimerization of HSA. In addition, uremic HSA had shown impaired ligand-binding capability such as haemin (0.37 × 107/M vs 2.18 × 107/M, P < 0.001), bilirubin (0.08 × 106/M vs 0.15 × 106/M, P < 0.05) and cis-parinaric acid (3.8 × 107/M vs 2.9 × 107/M, P < 0.05). Furthermore, using two different systems namely copper mediated oxidation of human low density lipoproteins and the free radicals mediated haemolysis test, we have demonstrated that the observed changes of uremic HSA can affect its antioxidant properties.In conclusion, the present study demonstrated that the quality and integrity of HSA molecule in dialysis patients were subtly altered and impaired its biological properties. Oxidative alterations of this major plasma protein might adversely affect its vasculoprotective effects in dialysis patients.