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Am J Nephrol. 2018;47(2):72-83. doi: 10.1159/000486968. Epub 2018 Feb 13.

Positive Iron Balance in Chronic Kidney Disease: How Much is Too Much and How to Tell?

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Division of Nephrology, Indiana University Health, Indianapolis, Indiana, USA.
Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA.
DaVita Kidney Care, Denver, Colorado, USA.
Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
Department of Laboratory Medicine, Boston Children's Hospital and Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin, Berlin, Germany.
Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA.
Department of Renal Medicine, King's College Hospital, Denmark Hill, London, United Kingdom.
Cardiology Service, Hospital Clínico Universitario, INCLIVA, CIBERCV and University of Valencia, Valencia, Spain.
NorthStar Strategic Consulting, LLC, Gladstone, New Jersey, USA.
Division of Cardiology, Children's Hospital Los Angeles, Los Angeles, California, USA.



Regulation of body iron occurs at cellular, tissue, and systemic levels. In healthy individuals, iron absorption and losses are minimal, creating a virtually closed system. In the setting of chronic kidney disease and hemodialysis (HD), increased iron losses, reduced iron absorption, and limited iron availability lead to iron deficiency. Intravenous (IV) iron therapy is frequently prescribed to replace lost iron, but determining an individual's iron balance and stores can be challenging and imprecise, contributing to uncertainty about the long-term safety of IV iron therapy.


Patients on HD receiving judicious doses of IV iron are likely to be in a state of positive iron balance, yet this does not appear to confer an overt risk for clinically relevant iron toxicity. The concomitant use of iron with erythropoiesis-stimulating agents, the use of maintenance iron dosing regimens, and the reticuloendothelial distribution of hepatic iron deposition likely minimize the potential for iron toxicity in patients on HD. Key Messages: Because no single diagnostic test can, at present, accurately assess iron status and risk for toxicity, clinicians need to take an integrative approach to avoid iron doses that impose excessive exposure while ensuring sufficient replenishment of iron stores capable of overcoming hepcidin blockade and allowing for effective erythropoiesis.


Chronic kidney disease; Hemodialysis; Hepcidin; Iron; Iron overload; Iron storage disorder; Transferrin

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