Journal
NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 33, Issue 12, Pages 2234-2244Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfy190
Keywords
anemia; ferritin; hemodialysis; inflammation; iron; mortality
Categories
Funding
- Amgen
- Kyowa Hakko Kirin
- Baxter Healthcare
- AstraZeneca
- European Renal Association-European Dialysis & Transplant Association
- German Society of Nephrology
- Hexal
- Janssen
- Japanese Society for Peritoneal Dialysis
- Keryx
- Proteon
- Relypsa
- Roche
- Societa Italiana di Nefrologia
- Spanish Society of Nephrology
- Vifor Fresenius Medical Care Renal Pharma
- Agence Nationale de la Recherche (France)
- Canadian Institutes of Health Research (Canada)
- Ontario Renal Network (Canada)
- National Health & Medical Research Council (Australia)
- National Institute for Health Research via the Comprehensive Clinical Research Network (UK)
- National Institutes of Health (USA)
- Patient-Centered Outcomes Research Institute (USA)
- Thailand Research Foundation (Thailand)
- Chulalongkorn University Matching Fund (Thailand)
- King Chulalongkorn Memorial Hospital Matching Fund (Thailand)
- National Research Council of Thailand (Thailand)
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Background. The Kidney Disease: Improving Global Outcomes guidelines have cautioned against administering intravenous (IV) iron to hemodialysis patients with high serum ferritin levels due to safety concerns, but prior research has shown that the association between high ferritin and mortality could be attributed to confounding by malnutrition and inflammation. Our goal was to better understand the ferritin-mortality association and relative influence of IV iron and inflammation in the USA, where ferritin levels have recently increased dramatically, and in Europe and Japan, where ferritin levels are lower and anemia management practices differ. Methods. Data from 18 261 patients in Phases 4 and 5 (2009-15) of the international Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, were analyzed. Using Cox regression, we modeled the association between baseline ferritin and 1-year mortality with restricted cubic splines and assessed the impact of potential confounders. Results. Median ferritin levels were 718 ng/mL in the USA, 405 in Europe and 83 in Japan. High ferritin levels were associated with elevated mortality (relative to region-specific medians) in all three regions. The strength of this association was attenuated more by adjustment for malnutrition and inflammation than by IV iron and erythropoiesis-stimulating agent dose in each region. Conclusion. The utility of high ferritin as a biomarker for clinical risk due to excess iron stores may be limited, although caution regarding IV iron dosing to higher upper ferritin targets remains warranted. Research to resolve biomarker criteria for iron dosing, and whether optimal anemia management strategies differ internationally, is still needed.
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