Anemia of Chronic Kidney Disease: Forward to the Past

Abstract

2009 by the National Kidney Foundation, Inc. All rights reserved. 1548-5595/09/1602-0001$36.00/0 doi:10.1053/j.ackd.2008.12.001 This issue of Advances in Chronic Kidney Disease limits the broad topic of the anemia of chronic kidney disease (CKD) to 2 issues: (1) the reemergence of iron as a principal hematinic and (2) the clinical outcomes associated with iron use in CKD, the biological and practice-related causes of hyporesponsiveness and hemoglobin variability, the relationship between hemoglobin targets and erythropoiesis-stimulating agents (ESAs), and the future of anemia management in the United States, which may involve a host of new iron-containing ESAs. Phylacus, through the advice of Melampus the seer, cured his son Iphiclus of impotence by having him ingest iron melted from his broadsword. Despite the mythology of this original report of oral iron therapy, this element, for decades, remained the sole treatment for the anemia of chronic kidney disease. When iron therapy failed to elevate hemoglobin levels in end-stage renal disease (ESRD) patients, blood transfusion therapy was the only recourse for those individuals with obligate blood losses from the dialytic procedures and multiple venipunctures. Thus, survival for dialysis patients was perforce associated with the risk of transfusion-related hemosiderosis and/or hemachromatosis. The putative consequence of maintaining hemoglobin levels .6.5 to 7 g/dL, which today are considered suboptimal by any standard, were iron overload, manifested as hyperferritinemia, and, possibly, increased cardiovascular risk. The ‘‘iron hypothesis’’—cardiac dysfunction induced by iron overload—first posited by Sullivan in 1981 noted that males, in age-dependent