title: Data from the Dialysis Outcomes and Practice Patterns Study validate an association between high intravenous iron doses and mortality.
abstract: Intravenous (IV) iron is required for optimal management of anemia in the majority of hemodialysis (HD) patients. While IV iron prescription has increased over time, the best dosing strategy is unknown and any effect of IV iron on survival is unclear. Here we used adjusted Cox regression to analyze associations between IV iron dose and clinical outcomes in 32,435 HD patients in 12 countries from 2002 to 2011 in the Dialysis Outcomes and Practice Patterns Study. The primary exposure was total prescribed IV iron dose over the first 4 months in the study, expressed as an average dose/month. Compared with 100-199 mg/month (the most common dose range), case-mix-adjusted mortality was similar for the 0, 1-99, and 200-299 mg/month categories but significantly higher for the 300-399 mg/month (HR of 1.13, 95% CI of 1.00-1.27) and 400 mg/month or more (HR of 1.18, 95% CI of 1.07-1.30) groups. Convergent validity was proved by an instrumental variable analysis, using HD facility as the instrument, and by an analysis expressing IV iron dose/kg body weight. Associations with cause-specific mortality (cardiovascular, infectious, and other) were generally similar to those for all-cause mortality. The hospitalization risk was elevated among patients receiving 300 mg/month or more compared with 100-199 mg/month (HR of 1.12, 95% CI of 1.07-1.18). In light of these associations, a well-powered clinical trial to evaluate the safety of different IV iron-dosing strategies in HD patients is urgently needed.
authors: Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors: George R
authors: GR
authors: Bailie
authors: Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA.
authors: Maria
authors: M
authors: Larkina
authors: Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA.
authors: David A
authors: DA
authors: Goodkin
authors: 1] Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA [2] Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
authors: Yun
authors: Y
authors: Li
authors: Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA.
authors: Ronald L
authors: RL
authors: Pisoni
authors: Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA.
authors: Brian
authors: B
authors: Bieber
authors: College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
authors: Nancy
authors: N
authors: Mason
authors: Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA.
authors: Lin
authors: L
authors: Tong
authors: Department of Nephrology and Dialysis and Renal Transplant, Alessandro Manzoni Hospital, Lecco, Italy.
authors: Francesco
authors: F
authors: Locatelli
authors: Department of Renal Medicine, Middlemore Hospital, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors: Mark R
authors: MR
authors: Marshall
authors: Department of Metabolism, Endrocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Masaaki
authors: M
authors: Inaba
authors: 1] Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA [2] Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
authors: Bruce M
authors: BM
authors: Robinson
mesh_terms: D061605:Administration, Intravenous; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy; D005260:Female; D006801:Humans; D007501:Iron / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis / Q000401:mortality*; D015203:Reproducibility of Results
chemical_list: D007501:Iron