The relationship between the dose of continuous erythropoietin receptor activator and oxidative stress in hemodialysis patients

At present, there have been no reports on the dose-dependent effects of continuous erythropoietin receptor activator(CERA) therapy on oxidative stress and red blood cell membrane lipid peroxidation parameters in hemodialysis (HD) patients. The aim of our work was to evaluate whether the dose of CERA treatment affected lipid peroxidation and antioxidant system in HD patients. Methods. 38 HD patients were included in this single-center cross-sectional observational study. The study protocol was approved by a local Ethics Committee and all patients provided signed informed consent. The patients were stratified into quartiles (≤25% and ≥75%) according to the average dose of continuous erythropoietin receptor activator (CERA) and grouped in the following way: Group I (> 6 months of CERA treatment in a low dosage ≤ 50 μg/month, n = 20) and Group II (> 6 months of CERA treatment in a high dosage ≥ 125 μg/month, n = 18). Along with the standard diagnostic methods, we defined the content of malondialdehyde levels in the serum (MDAs) and erythrocytes (MDAe) spectrophotometrically as an indicator of lipid peroxidation. Such parameters as the concentration of ceruloplasmin (CP) and transferrin (TR) in the blood and total peroxidase activity (TPA) in erythrocyte were studied as the indicators of antioxidant system. In addition, we calculated the percentage of hemolysis, the RBC membrane permeability and oxidation coefficient. Results. We obtained heterogeneous results in assessing oxidative stress parameters. The significantly higher levels of CP (p = 0.007) and TR (p = 0.0003) were found in the patients treated with a high dosage CERA. TPA activity in erythrocyte in the patients of Group II was statistically higher compared to Group I (p = 0.02). Moreover, we determined a statistically high percentage of hemolysis (p = 0.03) and RBC membrane permeability (p ˂ 0.0001) in the patients who were treated with CERA in a dose ≥ 125 μg/month compared to other patients. Using the probit regression model, we established the dose-dependent effect of CERA on the level of RBC membranes permeability: χ2 = 21; p = ˂ 0.0001. Conclusions. We demonstrated that administration of CERA in a dose more 125 μg/month improved the antioxidant status in HD patients. But, at the same time, it increased the hemolysis and RBC membranes permeability. Our preliminary data pointing to the dose-dependent effect of CERA on the RBC membrane lipid peroxidation parameters require further confirmation.