Iron metabolism, iron deficiency, thrombocytosis, and the cardiorenal anemia syndrome.

In treating moderate to severe anemia of chronic kidney disease (CKD), oral iron is effective only in a minority of nondialysis patients. Intravenous iron is more effective and can raise levels of hemoglobin even without the use of erythropoiesis-stimulating agents (ESAs). Unfortunately, the current assays of iron status that are presently widely available are not especially helpful in predicting response. In patients on dialysis, i.v. iron is effective over a wide range of serum ferritin from <100 ng/ml to 800 ng/ml. None of the three available randomized controlled trials comparing oral with i.v. iron showed evidence of nephrotoxicity caused by i.v. iron. Iron deficiency is a risk factor for thrombocytosis and should, wherever possible, be avoided. Optimal coadministration of iron may reduce the risk for ESA-driven cardiovascular events. Increased total body iron stores (imperfectly reflected by serum ferritin levels in CKD) do not appear to be related to such events or hospitalization in CKD; it is unclear what other risk factors and mechanisms need to be considered. In the appreciable proportion of patients with both renal and cardiac dysfunction, management is further complicated by a vicious circle (which can be characterized as cardiorenal anemia syndrome) in which CKD, heart failure, and anemia exacerbate each other. In such patients, correction of anemia appears to improve cardiac function and quality of life without a greater risk for adverse events.