An indistinct balance: the safety and efficacy of parenteral iron therapy

Recombinant epoetin therapy and correction of the chronic anemia of renal failure have greatly reduced the number of red cell transfusions and hence the propensity to iron overload. The majority of HD patients require intravenous iron therapy to achieve the hematocrit levels that correspond to improved outcome measures. Although the short-term benefits of intravenous iron have been clearly defined, the long-term risks of intravenous iron are less well-defined. Iron overload before the availability of epoetin constituted a serious problem; our review of the literature does not decisively conclude that these patients had more serious bacterial infections or increased mortality when compared with their non-iron overloaded counterparts, unless chronic transfusion-related hepatic disease was superimposed. Specifically, no data unequivocally confirm that iron overload from parenteral iron contributes to all-cause patient morbidity or mortality. Furthermore, therapy that maintains intravenous iron optimal iron stores and replaces iron losses associated with the dialytic procedure does not engender iron overload in the carefully monitored patient. Optimized anemia therapy in ESRD requires individualized and specific application of epoetin and iron for each patient, and significant cost savings can result from such a strategy. Prospective studies are clearly necessary to define those parameters that reflect adequacy of iron storage in renal failure patients. We should develop alternative means of iron delivery and develop monitors that accurately discriminate between patients who will respond to additional iron therapy and those who will not. Whether ferritin should be supplanted by another parameter and whether iron itself poses an increased risk to those patients it has so beneficially served are issues that must be resolved. Until these answers are known, the importance of carefully crafted iron therapy cannot be overstated.