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 andcause erythropoietin resistance in haemodialysis patients with ironoverload. Controversy remains as to whether intravenous iron medication canimprove this hyporesponsiveness due to decreased iron availability, orwhether iron therapy will aggravate haemosiderosis. Intravenousadministration of ascorbic acid has been shown to effectively circumventresistant anaemia associated with iron overload in a small preliminarystudy. To elucidate further the possible mechanisms of this resistance, aparallel, comparative study was conducted to compare the effects ofintravenous iron and ascorbate therapies in iron-overloaded haemodialysispatients. Methods: Fifty haemodialysis patients withserum ferritin of >500 &mgr;g/l were randomly divided into twoprotocols. They were further stratified into controls (Control I, n=11) andintravenous iron group (IVFE, n=15) in protocol I; and into controls(Control II, n=12) and intravenous ascorbic acid group (IVAA, n=12) inprotocol II. Controls had a haematocrit of >30% and did not receiveany adjuvant therapy. IVFE and IVAA patients were hyporesponsive toerythropoietin and functionally iron deficient. Ferric saccharate (100 mgdose) was administered intravenously post-dialysis on five consecutivedialysis sessions in the first 2 weeks; and ascorbic acid (300 mg dose)thrice a week for 8 weeks. Red cell and iron metabolism indices wereexamined before and following therapy. Results: Meanvalues of haematocrit and transferrin saturation were significantly lower,and erythropoietin dose was higher in IVFE and IVAA patients compared tocontrols. Intravenous iron therapy neither improved erythropoiesis norreduced erythropoietin dose during 12 weeks. Iron metabolism indicessignificantly increased at 2 and 6 weeks, but decreased at 12 weeksreturning to the baselines. In contrast, mean haematocrit significantlyincreased from 25.8±0.5 to 30.6±0.6% with aconcomitant reduction of 20% in erythropoietin dose after 8 weeks ofascorbate therapy. Serum ferritin modestly fell but with no statisticalsignificance. The enhanced erythropoiesis paralleled a rise in transferrinsaturation from 27±3 to 48±6% and serum iron from70±11 to 107±19 &mgr;g/dl (P<0.05).Conclusions: Short term intravenous iron therapycannot resolve the issue of functional iron deficiency in haemodialysispatients with iron overload. Intravenous administration of ascorbic acidnot only facilitates iron release from storage sites, but also increasesiron utilization in the erythron. Our study draws attention to a potentialadjuvant therapy, intravenous ascorbic acid, to treaterythropoietin-hyporesponsive anaemia in iron-overloaded patients.