title: Intravenous iron exposure and mortality in patients on hemodialysis.
abstract: OBJECTIVE
  Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking, and observational studies have been limited by assessment of short-term exposure only and/or failure to assess cause-specific mortality. The associations between short- and long-term iron exposure on all-cause and cause-specific mortality were examined.
  
  
  METHODS
  The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008. Intravenous iron dose accumulations over 1-, 3-, and 6-month rolling windows were related to all-cause, cardiovascular, and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding.
  
  
  RESULTS
  Patients in the 1-month model cohort (n=14,078) were followed a median of 19 months, during which there were 27.6% all-cause deaths, 13.5% cardiovascular deaths, and 3% infection-related deaths. A reduced risk of all-cause mortality with receipt of >150-350 (hazard ratio, 0.78; 95% confidence interval, 0.64 to 0.95) or >350 mg (hazard ratio, 0.79; 95% confidence interval, 0.62 to 0.99) intravenous iron compared with >0-150 mg over 1 month was observed. There was no relation of 1-month intravenous iron dose with cardiovascular or infection-related mortality and no relation of 3- or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality. There was a nonstatistically significant increase in infection-related mortality with receipt of >1050 mg intravenous iron in 3 months (hazard ratio, 1.69; 95% confidence interval, 0.87 to 3.28) and >2100 mg in 6 months (hazard ratio, 1.59; 95% confidence interval, 0.73 to 3.46).
  
  
  CONCLUSIONS
  Among patients on incident dialysis, receipt of ≤ 1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause, cardiovascular, or infection-related mortality. However, nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of >1050 mg in 3 months or >2100 mg in 6 months. Randomized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material. dmiskulin@tuftsmedicalcenter.org.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Miskulin
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Navdeep
authors.initials: N
authors.lastname: Tangri
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Karen
authors.initials: K
authors.lastname: Bandeen-Roche
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Aidan
authors.initials: A
authors.lastname: McDermott
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Klemens B
authors.initials: KB
authors.lastname: Meyer
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Patti L
authors.initials: PL
authors.lastname: Ephraim
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Wieneke M
authors.initials: WM
authors.lastname: Michels
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Jaar
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Deidra C
authors.initials: DC
authors.lastname: Crews
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Scialla
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Sozio
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Tariq
authors.initials: T
authors.lastname: Shafi
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Albert W
authors.initials: AW
authors.lastname: Wu
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Courtney
authors.initials: C
authors.lastname: Cook
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: L Ebony
authors.initials: LE
authors.lastname: Boulware
mesh_terms: D061605:Administration, Intravenous; D002318:Cardiovascular Diseases / Q000401:mortality*; D005260:Female; D005293:Ferritins / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D007239:Infections / Q000401:mortality*; D007501:Iron / Q000008:administration & dosage / Q000009:adverse effects*; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects* / Q000401:mortality*; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D005293:Ferritins; D007501:Iron
keywords: anemia; epidemiology and outcomes; hemodialysis