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  • Review Article
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Iron supplementation to treat anemia in patients with chronic kidney disease

Nature Reviews Nephrology volume 6, pages 699–710 (2010)Cite this article

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A Correction to this article was published on 27 January 2012

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Abstract

Iron deficiency is prevalent in patients with chronic kidney disease (CKD), and use of oral and intravenous iron in patients with CKD who do not require dialysis might obviate or delay the need for treatment with eythropoiesis-stimulating agents (ESAs). Patients on hemodialysis have lower intestinal iron absorption, greater iron losses, and require greater iron turnover to maintain the ESA-driven red cell mass than do healthy individuals. In these patients, intravenous iron reduces ESA dose requirements and increases the likelihood of maintaining levels of hemoglobin within the desired range. Oral iron is inferior to intravenous iron in patients on hemodialysis, in part because elevated serum levels of hepcidin prevent intestinal absorption of iron. Increased levels of hepcidin also impair the normal recycling of iron through the reticuloendothelial system. Levels of serum ferritin and transferrin saturation below 450 pmol/l and 20%, respectively are indicative of iron deficiency, but values above the normal range lack diagnostic value in patients with CKD on dialysis. The availability of various iron preparations and new developments in delivering iron should enable adequate provision of iron to patients with CKD. This Review examines the efficacy, safety and use of iron supplementation therapy for the treatment of anemia in patients with CKD.

Key Points

  • Iron deficiency is prevalent in patients with chronic kidney disease (CKD) and should be treated

  • Inconsistent and inadequate absorption of oral iron frequently leads to the need for administration of intravenous iron

  • Hepcidin (levels of which are frequently increased in patients with CKD) impairs iron absorption and the normal recycling of iron through the reticuloendothelial system

  • Low levels of serum ferritin and transferrin saturation indicate iron deficiency, but values in or above the normal range lack diagnostic value

  • Frequent, small repeat doses of intravenous iron are more effective than infrequent, large doses for maintaining levels of hemoglobin and reducing the requirement for erythropoiesis-stimulating agents (ESAs)

  • Relative thrombocytosis (owing to iron deficiency) might contribute to the increased cardiovascular risk seen with high ESA doses

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Figure 1: Iron distribution in the average adult.
Figure 2: Erythropoiesis.
Figure 3: Photomicrographs of erythroblastic islands, where erythroid precursors proliferate, differentiate and enucleate.
Figure 4: Microphotograph of bone marrow staining for iron.
Figure 5: Serum ferritin level and reticuloendothelial iron accumulation in patients on hemodialysis treated for anemia with blood transfusions in the pre-ESA era.
Figure 6: A treatment algorithm for the management of anemia in patients with CKD.

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Change history

  • 12 December 2011

    In the version of this article initially published online, incorrect volume and page numbers were given for reference 90. The correct reference is Sargent, J. A. & Acchiardo, S. R. Iron requirements in hemodialysis. Blood Purif. 22, 112–123 (2004). The error has been corrected for the HTML and PDF versions of the article.

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Authors and Affiliations

  1. Division of Nephrology and Hypertension, Henry Ford Hospital, CFP 511, 2799 West Grand Boulevard, Detroit, 48301, MI, USA

    Anatole Besarab

  2. Division of Nephrology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, 63110, MO, USA

    Daniel W. Coyne

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A. Besarab and D. W. Coyne contributed equally to all aspects of this manuscript.

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Correspondence to Anatole Besarab.

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A. Besarab has acted as a consultant for Affymax, AMAG Pharmaceuticals, Amgen, Hoffman–La Roche and Watson Pharmaceuticals, is a member of the speakers' bureau or has received honoraria from AMAG Pharmaceuticals, Hoffman–La Roche and Watson Pharmaceuticals and has received grant or research support from Affymax, AMAG Pharmaceuticals and Hoffman–La Roche. D. W. Coyne has acted as a consultant for Pharmacosmos, Sanofi–Aventis and Watson Pharmaceuticals and is a member of the speakers' bureau or has received honoraria from AMAG Pharmaceuticals and Watson Pharmaceuticals.

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Besarab, A., Coyne, D. Iron supplementation to treat anemia in patients with chronic kidney disease. Nat Rev Nephrol 6, 699–710 (2010). https://doi.org/10.1038/nrneph.2010.139

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