Erythropoietin Resistance Development in Hemodialysis Patients: The Role of Oxidative Stress

Oxidative stress (OS) is considered a significant risk factor for the development of anemia in patients treated by regular hemodialysis (HD). Moreover, OS represents a risk factor for the development of erythropoietin (EPO) resistance in these patients. The aim of this study was to examine the role of OS regarding EPO resistance development in patients treated by regular HD. 96 patients treated with standard HD and on-line hemodiafiltration were included in this study. The patients were treated with short-acting and long-acting EPOs for anemia. The concentration of superoxide anion radical, hydrogen peroxide, thiobarbituric acid reactive substances, and nitric oxide in the form of nitrites and the activity of catalase, superoxide dismutase and reduced glutathione were measured in patients' blood spectrophotometrically. Standard biochemical analysis, inflammatory markers, nutritional status, HD parameters, and erythropoietin resistance index were also determined. Patients with resistance to short-acting EPO had significantly lower concentration of hemoglobin in the blood and hematocrit value, a significantly higher serum ferritin concentration, and significantly lower catalase activity in erythrocytes than patients without EPO resistance. Patients with resistance to long-acting EPO have a significantly lower hemoglobin concentration in the blood, hematocrit values, and serum concentration of prealbumin and vitamin D, as well as significantly higher concentration of C-reactive protein, superoxide anion, and hydrogen peroxide concentration than those without resistance. OS significantly contributes to EPO resistance development. OS, higher ferritin and CRP levels, lower hemoglobin, hematocrit and prealbumin levels, and vitamin D deficiency represent significant risk factors for EPO resistance development in HD patients.