title: Iron supplementation and mortality in incident dialysis patients: an observational study.
abstract: BACKGROUND
  Studies on the association between iron supplementation and mortality in dialysis patients are rare and conflicting.
  
  
  METHODS
  In our observational single-center cohort study (INVOR study) we prospectively studied 235 incident dialysis patients. Time-dependent Cox proportional hazards models using all measured laboratory values for up to 7.6 years were applied to study the association between iron supplementation and all-cause mortality, cardiovascular and sepsis-related mortality. Furthermore, the time-dependent association of ferritin levels with mortality in patients with normal C-reactive protein (CRP) levels (<0.5 mg/dL) and elevated CRP levels (≧0.5 mg/dL) was evaluated by using non-linear P-splines to allow flexible modeling of the association.
  
  
  RESULTS
  One hundred and ninety-one (81.3%) patients received intravenous iron, 13 (5.5%) patients oral iron, whereas 31 (13.2%) patients were never supplemented with iron throughout the observation period. Eighty-two (35%) patients died during a median follow-up of 34 months, 38 patients due to cardiovascular events and 21 patients from sepsis. Baseline CRP levels were not different between patients with and without iron supplementation. However, baseline serum ferritin levels were lower in patients receiving iron during follow up (median 93 vs 251 ng/mL, p<0.001). Iron supplementation was associated with a significantly reduced all-cause mortality [HR (95%CI): 0.22 (0.08-0.58); p = 0.002] and a reduced cardiovascular and sepsis-related mortality [HR (95%CI): 0.31 (0.09-1.04); p = 0.06]. Increasing ferritin concentrations in patients with normal CRP were associated with a decreasing mortality, whereas in patients with elevated CRP values ferritin levels>800 ng/mL were linked with increased mortality.
  
  
  CONCLUSIONS
  Iron supplementation is associated with reduced all-cause mortality in incident dialysis patients. While serum ferritin levels up to 800 ng/mL appear to be safe, higher ferritin levels are associated with increased mortality in the setting of concomitant inflammation.
authors.affiliation: Department of Nephrology and Dialysis, Feldkirch Academic Teaching Hospital, Feldkirch, Austria; Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Zitt
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria; Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Gisela
authors.initials: G
authors.lastname: Sturm
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Neyer
authors.affiliation: Department of Nephrology and Dialysis, Feldkirch Academic Teaching Hospital, Feldkirch, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Knoll
authors.affiliation: Department of Nephrology and Dialysis, Feldkirch Academic Teaching Hospital, Feldkirch, Austria; Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Lhotta
authors.affiliation: Department of Internal Medicine VI (Infectious Diseases, Immunology, Rheumatology, Pneumology), Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Günter
authors.initials: G
authors.lastname: Weiss
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007501:Iron / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D018805:Sepsis / Q000401:mortality*
chemical_list: D007501:Iron