ERYTHROPOIETIN AND OXIDATIVE STRESS IN HEMODIALYSIS - BENEFICIAL-EFFECTS OF VITAMIN-E SUPPLEMENTATION

Oxidative stress can produce profound alterations to cellular membrane lipids, impairing cell metabolism and viability. This phenomenon, pre viously observed in haemodialysis patients, has been proposed as a sig nificant factor in regard to haemodialysis-related shortened red blood cells (RBC) survival. In the present study, several parameters associ ated with oxidative stress were evaluated in a group of haemodialysis patients either receiving erythropoietin therapy (n = 12, mean erythro poietin dose 88 +/- 24 U/kg/week) or not receiving such therapy (n = 3 0), and in 38 controls. Malonyldialdehyde (MDA, nmol/ml), an end-produ ct of lipid peroxidation, and RBC antioxidant systems were measured, i ncluding RBC alpha-tocopherol (RBC vitamin E, mg/l), RBC glutathione ( GSH, nmol/mgHb), and RBC superoxide dismutase activity (SOD. U/mgHb). Plasma vitamin E concentrations were also evaluated. Finally, oral vit amin E supplementation (500 mg daily), an exogenous antioxidant, was a dministered for 6 months to seven patients from the dialysis group rec eiving erythropoietin while oxidative parameters were repeatedly evalu ated and erythropoietin requirements monitored, in order to appreciate the therapeutic relevance of an antioxidant supplementation. An eleva tion of serum MDA was observed in all haemodialysis patients and a sig nificant decrease in RBC vitamin E, despite normal serum vitamin E lev els. Furthermore, the reduction in RBC vitamin E was more important in patients treated with erythropoietin. Vitamin E supplementation resul ted in a significant increase in RBC vitamin E (from 0.3 +/- 0.1 to 1. 2 +/- 0.2 mg/l of pellet) and a reduction in erythropoietin dose (from 93 +/- 24 to 74 +/- 26 U/kg/week) while maintaining stable haemoglobi n concentrations. These results suggest that the oxidative stress coul d be one of the resistance factors to erythropoietin response in haemo dialysis and that vitamin E supplementation could have a sparing effec t on erythropoietin dosage requirement.