Parameters indicating oxidative stress after complete correction of renal anemia

Chronic hemodialysis (HD) patients are exposed to oxidative stress, induced at least in part by immunological reactions, the metabolic acidosis and th e hemodialysis itself Increased levels of malondialdehyde (MDA) were demons trated in these patients, indicating an increase in lipid peroxidation (LPO ). The plasma levels of MDA correlated with the degree of anemia and were l ower in patients with a partially corrected anemia under therapy with recom binant human erythropoietin (rhEPO), compared to patients with severe anemi a. Therefore, anemia itself may contribute to free-radical formation. Furth ermore, anemia is associated with a decrease in reduced glutathione (GSH), one of the important antioxidants in human blood, paralleled by increased l evels of glutathiondisulfide (GSSG). Oxidative stress may contribute to a d ecrease in erythrocyte deformability, increased levels of oxidated hemoglob in and a decreased erythrocyte survival time. Free radicals cah inactivate enzymes and react with structures like proteins, RNA or DNA. An increase in LDL oxidation is associated with a higher risk for atherosclerosis. Theref ore, we investigated whether the complete correction of renal anemia by mea ns of rhEPO-therapy can reduce the free radical formation and increase the levels of antioxidants. MDA, GSH und GSSG were measured in patients with a normal hematocrit (Hct greater than or equal to 0.4), receiving rhEPO-thera py and compared to patients with mild (Hct 0.3 - 0.39) and severe anemia (H ct < 0.3). The patients were comparable in age, sex and body weight, but th e patients with a normal Hct were significantly longer on HD (74.0 +/- 70.3 vs. 23.0 +/- 30.9, respectively 30.6 +/- 34.8 months, p < 0.05) and receiv ed significantly lower doses of iron (35.7 +/- 19.5 vs. 55.4 +/- 26.0, resp ectively 80.0 rt:47.1, p < 0.05 [mg/week]) and rhEPO (68.9 +/- 63.6 vs. 106 .5 +/- 63.9, respectively 152.8 +/- 86.0, p < 0.05 [IU/kg KGxweek]). The MD A concentration was significantly lower in the normal Hct patient group com pared to anemic patients (1.54 +/- 0.27 vs. 1.98 +/- 0.52, respectively 2.2 3 +/- 0.93, p = 0.01 [mu Mol/l]). The difference between the groups of anem ic patients was not significant. Comparing the 3 patient groups, no differe nces were found in GSH and GSSG, when the concentrations were corrected for Hct. The whole blood concentration were significantly higher in patients w ith Hct greater than or equal to 0.4 and Hct 0.3 - 0.39 than in patients wi th Hct < 0.3 (0.97 +/- 0.42 vs. 1.03 +/- 0.38, respectively 0.62 +/- 0.34, p less than or equal to 0.05 [mu Mol/ml] and 14.57 +/- 6.06 vs. 13.07 +/- 5 .18, respectively 7.28 +/- 3.64, p less than or equal to 0.05 [mu Mol/l]). Conclusion: In comparison to anemic patients, MDA levels are significantly decreased in HD patients after complete correction of renal anemia, indicat ing a reduction in free radical formation and the antioxidative capacity of whole blood is significantly increased, implicating positive aspects of rh EPO therapy in free radical metabolism.