Anemia associated with extraerythrocytic oxidative stress damage mediated by neutrophil superoxide anion production in chronic renal failure patients undergoing hemodialysis

Anemia in patients with uremia undergoing hemodialysis (HD) is a complex process that is dependent on erythropoiesis associated with erythropoietin and iron availability. Published information about an extra erythrocytic factor in the data concerning HD and the underlying mechanism by which anemia occurs remain unclear. The aim of this study was to investigate the superoxide anion generation by polymorphonuclear neutrophils and red blood cell (RBC) lipid peroxidizability as well as the possible association between these parameters and anemia in patients undergoing HD. Blood was collected from 15 volunteers prior to and following HD, and hematological data showed significant anemia at both time points. RBC lipid peroxidizability and neutrophil anion superoxide production, as evaluated by kinetics analysis, revealed increased initial and maximal velocity before and after HD. Plasma malondialdehyde (MDA) and antioxidant levels in the patient group were higher than those in the control group. RBC superoxide dismutase and catalase activities did not differ between groups. There was a significant correlation between increased RBC lipid peroxidizability and superoxide anion production and anemia in patients undergoing HD. The individual variation in plasma MDA was accompanied by superoxide anion production. The RBC lipid peroxidizability, mediated by neutrophil-generated superoxide anions, seems to be a plausible mechanism for explaining, in part, the extraerythrocytic damage that leads to anemia in patients on HD.

► We evaluated lipid peroxidizability in erythrocytes of patients undergoing hemodialysis.
► We demonstrated the direct involvement of superoxide anion produced by neutrophils in the pre hemolytic oxidative damage of red blood cells.
► This damage leads to anemia in hemodialysis patients.
► A positive correlation between lipid peroxidizability of red blood cells with both anemia and superoxide generation by neutrophils may confirm such mechanism.