The influence of vitamin E supplementation on erythropoietin responsiveness in chronic hemodialysis patients with low levels of erythrocyte superoxide dismutase

Abstract

About 12-15 % of hemodialysis patients have a poor response to recombinant human erythropoietin (rHuEPO). The aim of this prospective study was to examine the influence of oxidative stress and vitamin E supplementation on rHuEPO responsiveness in chronic hemodialysis patients. Sixty-five hemodialysis patients treated with rHuEPO were studied. Those with iron deficiency, blood loss, malignancy, vitamin B12 and folate deficiency, severe hyperparathyroidism, liver cirrhosis, and congestive heart failure were excluded. Twenty-one healthy volunteers served as a control group. Malondialdehyde, carbonyl proteins, erythrocyte superoxide dismutase (SOD), ceruloplasmin, and serum antioxidant capacity were measured. Values of SOD > 150 U/ml were considered as normal. Patients with SOD < 150 U/ml were divided in two groups: group A (n = 11): treated with vitamin E 400 mg/day (600 IU/day) for 8 weeks; group B (n = 13): not treated. A third, group C consisted of patients with normal SOD. rHuEPO doses (U/kg/week) were recorded. rHuEPO responsiveness index was calculated as rHuEPO U/week/hematocrit. A poor response was defined as a rHuEPO responsiveness index >200. SOD positively correlated with hemoglobin (p = 0.0018, R = 0.337) and negatively with rHuEPO responsiveness index (p = 0.0122, R = 0.319). Vitamin E-treated patients from group A exhibited significantly increased hemoglobin levels as compared to initial values (10.5 ± 0.3 vs. 8.6±0.4, p = 0.002). In comparison with group B, the vitamin E-treated patients displayed a higher hemoglobin (10.5 ± 0.3 vs. 9.4 ± 0.3, p = 0.04), had a lower rHuEPO dose (85.7 ± 7.4 vs. 136.8 ± 13.8, p = 0.025), and a significantly improved rHuEPO responsiveness (rHuEPO responsiveness index 177.9 ± 28.6 vs. 314.1 ± 34.0, p = 0.006). Patients from group A significantly improved their rHuEPO responsiveness after vitamin E therapy as compared to baseline (rHuEPO responsiveness index 177.9 ± 28.6 vs. 271.7 ± 30.3, p = 0.034). We conclude that lower values of SOD correlate with lower hemoglobin, higher rHuEPO dose and poor response to rHuEPO in chronic hemodialysis patients. Vitamin E supplementation significantly improves rHuEPO responsiveness, increases hemoglobin level, and decreases rHuEPO dose.