A parallel, comparative study of intravenous iron versus intravenous ascorbic acid for erythropoietin-hyporesponsive anaemia in haemodialysis patients with iron overload

Background: Functional iron deficiency may develop and cause erythropoietin resistance in haemodialysis patients with iron overload. Controversy remains as to whether intravenous iron medication can improve this hyporesponsiveness due to decreased iron availability, or whether iron therapy will aggravate haemosiderosis. Intravenous administration of ascorbic acid has been shown to effectively circumvent resistant anaemia associated with iron overload in a small preliminary study. To elucidate further the possible mechanisms of this resistance, a parallel, comparative study was conducted to compare the effects of intravenous iron and ascorbate therapies in iron-overloaded haemodialysis patients. Methods: Fifty haemodialysis patients with serum ferritin of >500 &mgr;g/l were randomly divided into two protocols. They were further stratified into controls (Control I, n=11) and intravenous iron group (IVFE, n=15) in protocol I; and into controls (Control II, n=12) and intravenous ascorbic acid group (IVAA, n=12) in protocol II. Controls had a haematocrit of >30% and did not receive any adjuvant therapy. IVFE and IVAA patients were hyporesponsive to erythropoietin and functionally iron deficient. Ferric saccharate (100 mg dose) was administered intravenously post-dialysis on five consecutive dialysis sessions in the first 2 weeks; and ascorbic acid (300 mg dose) thrice a week for 8 weeks. Red cell and iron metabolism indices were examined before and following therapy. Results: Mean values of haematocrit and transferrin saturation were significantly lower, and erythropoietin dose was higher in IVFE and IVAA patients compared to controls. Intravenous iron therapy neither improved erythropoiesis nor reduced erythropoietin dose during 12 weeks. Iron metabolism indices significantly increased at 2 and 6 weeks, but decreased at 12 weeks returning to the baselines. In contrast, mean haematocrit significantly increased from 25.8±0.5 to 30.6±0.6% with a concomitant reduction of 20% in erythropoietin dose after 8 weeks of ascorbate therapy. Serum ferritin modestly fell but with no statistical significance. The enhanced erythropoiesis paralleled a rise in transferrin saturation from 27±3 to 48±6% and serum iron from 70±11 to 107±19 &mgr;g/dl (P<0.05). Conclusions: Short term intravenous iron therapy cannot resolve the issue of functional iron deficiency in haemodialysis patients with iron overload. Intravenous administration of ascorbic acid not only facilitates iron release from storage sites, but also increases iron utilization in the erythron. Our study draws attention to a potential adjuvant therapy, intravenous ascorbic acid, to treat erythropoietin-hyporesponsive anaemia in iron-overloaded patients.