Iron supplementation and mortality in incident dialysis patients: an observational study

Emanuel Zitt; Gisela Sturm; Florian Kronenberg; Ulrich Neyer; Florian Knoll; Karl Lhotta; Günter Weiss

doi:10.1371/journal.pone.0114144

Iron supplementation and mortality in incident dialysis patients: an observational study

PLoS One. 2014 Dec 2;9(12):e114144. doi: 10.1371/journal.pone.0114144. eCollection 2014.

Authors

Emanuel Zitt¹, Gisela Sturm², Florian Kronenberg³, Ulrich Neyer⁴, Florian Knoll⁵, Karl Lhotta¹, Günter Weiss⁶

Affiliations

¹ Department of Nephrology and Dialysis, Feldkirch Academic Teaching Hospital, Feldkirch, Austria; Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
² 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.
³ Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
⁴ Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
⁵ Department of Nephrology and Dialysis, Feldkirch Academic Teaching Hospital, Feldkirch, Austria.
⁶ Department of Internal Medicine VI (Infectious Diseases, Immunology, Rheumatology, Pneumology), Innsbruck Medical University, Innsbruck, Austria.

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.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cardiovascular Diseases / mortality*
Cohort Studies
Female
Humans
Iron / administration & dosage*
Male
Middle Aged
Renal Dialysis / adverse effects*
Sepsis / mortality*

Substances

Iron

Grants and funding

This study was supported by a grant from Hans Drexel to the Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT to KL) and by a grant from the Austrian National Bank (Project 13662 to FK) and the Austrian Science Fund FWF (TRP-188 to GW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.