Greater use of ESAs and iron at lower hematocrit levels decrease risk of death for hemodialysis patients

Greater use of erythropoiesis-stimulating agents (ESAs) and more frequent use of iron at lower hematocrit levels (the proportion of the blood that consists of red blood cells) was associated with a decreased risk of death for hemodialysis patients, according to a study in the March 3 issue of JAMA.

"Appropriate use of ESAs [which stimulate red blood cell production] and intravenous iron can effectively manage the anemia of chronic kidney disease and end-stage renal disease (ESRD), but several randomized trials have reported an increased risk of mortality and cardiovascular events in patients treated to achieve higher hematocrit levels. The earlier of these reports prompted the U.S. Food and Drug Administration in March 2007 to issue a black box warning for all ESAs recommending that they be used at the lowest level necessary to prevent transfusions," the authors write. There is disagreement regarding the appropriate management of anemia in ESRD.

M. Alan Brookhart, Ph.D., of the University of North Carolina, Chapel Hill, and colleagues assessed the 1-year mortality risk associated with different dialysis center-level patterns of ESA and intravenous iron use for 269,717 new hemodialysis patients. Using data from Medicare's ESRD program (1999-2007), the researchers characterized each U.S. dialysis center's annual anemia management practice by estimating its typical use of ESAs and intravenous iron in hemodialysis patients within 4 hematocrit categories.

After adjustment for various factors, the researchers found that certain patterns of ESA and iron use by dialysis centers were associated with different mortality risks among new patients at those centers. Centers that used larger doses of ESAs in patients with hematocrit less than 30 percent achieved lower mortality rates, while mortality rates were increased in centers that used larger ESA doses in patients with hematocrit between 33 percent and 35.9 percent and in those with hematocrit of 36 percent or higher. "We observed decreased mortality in centers that used iron more frequently in patients with hematocrit less than 30 percent and in patients with hematocrit between 30 percent and 32.9 percent. We also observed increasing mortality rates in centers that used iron more frequently in patients with hematocrit levels of 36 percent or higher," the authors write.

"Further observational and experimental studies are needed to help identify optimal treatment algorithms for both ESAs and iron that maximize clinical benefit while minimizing adverse outcomes."
(JAMA. 2010;303[9]:857-864. Available pre-embargo to the media at www.jamamedia.org)