title: Considerations and challenges in defining optimal iron utilization in hemodialysis.
abstract: Trials raising concerns about erythropoiesis-stimulating agents, revisions to their labeling, and changes to practice guidelines and dialysis payment systems have provided strong stimuli to decrease erythropoiesis-stimulating agent use and increase intravenous iron administration in recent years. These factors have been associated with a rise in iron utilization, particularly among hemodialysis patients, and an unprecedented increase in serum ferritin concentrations. The mean serum ferritin concentration among United States dialysis patients in 2013 exceeded 800 ng/ml, with 18% of patients exceeding 1200 ng/ml. Although these changes are broad based, the wisdom of these practices is uncertain. Herein, we examine influences on and trends in intravenous iron utilization and assess the clinical trial, epidemiologic, and experimental evidence relevant to its safety and efficacy in the setting of maintenance dialysis. These data suggest a potential for harm from increasing use of parenteral iron in dialysis-dependent patients. In the absence of well powered, randomized clinical trials, available evidence will remain inadequate for making reliable conclusions about the effect of a ubiquitous therapy on mortality or other outcomes of importance to dialysis patients. Nephrology stakeholders have an urgent obligation to initiate well designed investigations of intravenous iron in order to ensure the safety of the dialysis population.
authors.affiliation: Renal Division and dcharytan@partners.org.
authors.forename: David M
authors.initials: DM
authors.lastname: Charytan
authors.affiliation: Pharmacy Practice, Brigham & Women's Hospital, Boston, Massachusetts; Albany College of Pharmacy and Health Sciences, Albany, New York;
authors.forename: Amy Barton
authors.initials: AB
authors.lastname: Pai
authors.affiliation: Renal Division and Toronto General Hospital, University Health Network, Ontario, Canada;
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Chan
authors.affiliation: Renal Division and Washington University, Saint Louis, Missouri;
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Coyne
authors.affiliation: Nephrology Division, Departments of Medicine and Vanderbilt University Medical Center, Nashville, Tennessee;
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Hung
authors.affiliation: Nephrology Division, Departments of Medicine and University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
authors.affiliation: Renal Division and Hofstra North Shore-LIJ School of Medicine, Great Neck, New York.
authors.forename: Steven
authors.initials: S
authors.lastname: Fishbane
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005293:Ferritins / Q000378:metabolism; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D058085:Iron Compounds / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D058085:Iron Compounds; D004921:Erythropoietin; D005293:Ferritins
keywords: ESRD; anemia; dialysis; erythropoietin