It's Time to Compare Anemia Management Strategies in Hemodialysis

Randomized trials of intravenous (IV) iron have repeatedly demonstrated a rise in hemoglobin (Hgb), an erythropoiesis-stimulating agent (ESA) dose-sparing effect, and apparent safety. Such benefits were confirmed in a trial in hemodialysis patients with high ferritin receiving high ESA doses. But long-term randomized safety trials of IV iron have not been performed, which critics blame on IV iron manufacturers, leading some to question widespread use of IV iron to optimize Hgb and reduce ESA dose. ESAs increase risks of cardiovascular events and death when used to target higher versus lower Hgb values. Association studies report increasing risk with higher ESA doses at approved Hgb targets. Nevertheless, ESAs remain essential in dialysis practice. After early termination of the Normal Hematocrit Trial in 1996, analysis suggested IV iron was a risk factor for harm. In 2006, dangers related to ESA use were recognized. Trial results demonstrating IV iron was efficacious and ESA-sparing even at higher serum ferritin have intensified the focus on iron safety. Two principal alternatives in the management of anemia among dialysis patients are: (1) more intensive ESA dosing sparing iron dosing and (2) more intensive iron dosing sparing ESA dosing. Extended safety trials of IV iron versus no iron will become confounded by ESA dose differences between arms. Similarly higher ESA doses are associated with increased mortality risk, but trials comparing ESA doses will be confounded by Hgb differences. Rather than focus on individual products, we should perform trials comparing anemia management strategies to assess safety, efficacy, and cost. Clin J Am Soc Nephrol 5: 740-742, 2010. doi: 10.2215/CJN.02490409