Iron and cardiac disease in the end-stage renal disease setting.

Erythropoietin (EPO) therapy and appropriate iron administration are important aspects for managing the anemia of end-stage renal disease (ESRD). Achieving target hemoglobin levels of 11 to 12 g/dL and optimizing iron balance should improve clinical outcomes and increase patient quality of life. However, concerns have been raised about parenteral iron supplementation leading to excessively high iron levels, which may induce increased oxidative stress and risk for cardiovascular disease. Increased oxidative stress is often already present in patients with chronic renal disease and in patients with ESRD undergoing hemodialysis. The "iron hypothesis" proposes that excess iron is associated with increased risk for cardiac disease. While some studies have found an association between high iron levels or increased iron consumption with elevated risk for cardiac disease in subjects without renal disease, others have not found this association. Indeed, several studies suggest that achievement of target hematocrit levels in ESRD patients improves several clinical outcomes and that anemia itself is a risk factor for cardiac disease. Well-designed prospective studies are needed before the relationship between supplemental iron administration, excess iron, and cardiac disease can be firmly established.