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Cited by 71Iron Metabolism and DisordersErythropoietin and Anemia TreatmentDialysis and Renal Disease Management

Iatrogenic Iron Overload in Dialysis Patients at the Beginning of the 21st Century

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Rostoker, Guy, Vaziri, Nosratola D., Fishbane, Steven·2016·Drugs
DOI 10.1007/s40265-016-0569-0PMC PMC4848337
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Abstract

Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a 'second hit' on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients.

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  • Minihepcidins may have therapeutic potential in patients with primary iron overload due to hepcidin deficiency (e.g., hereditary hemochromatosis) and in patients with iatrogenic iron overload who still produce endogenous hepcidin.

    “Thus, minihepcidins may have therapeutic potential not only in patients with primary iron overload due to hepcidin deficiency (eg, hereditary hemochromatosis), but also in patients with iatrogenic iron overload (dialysis patients,20 patients with hemolytic anemias,21 transfused patients, etc) who still produce endogenous hepcidin.”

    From Endogenous hepcidin and its agonist mediate resistance to selected infections by clearing non-transferrin-bound iron (2017) · cites this paper as [20]

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Sorted by citations

Authors
Rostoker, G., Vaziri, N. D., & Fishbane, S.
Affiliations
  • University of California, Irvine (US)
  • Northwell Health (US)
Corresponding author
Rostoker, Guy
ORCID
Venue
Drugs
Publisher
Springer Science and Business Media LLC
Published
2016-04-18
Volume
76
Issue
7
Pages
741-757
ISSN
  • 0012-6667 (ISSN-L)
  • 1179-1950
DOI
10.1007/s40265-016-0569-0
PMC
PMC4848337
OpenAlex
W2340183923
Cited by
71
References
2
Citations by year
2026: 2 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 11 · 2020: 8 · 2019: 9 · 2018: 3 · 2017: 13 · 2016: 3
FWCI
1.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Drugs (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
RAMSAY-Générale de Santé
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
Keywords
hemodialysis patients, intravenous iron, liver iron concentration, hepcidin, cardiovascular events, sudden death, erythropoiesis-stimulating agents, fibroblast growth factor 23, oxidative stress, myocardial iron deposition, hereditary hemochromatosis
MeSH terms
Hematinics, Renal Dialysis, Humans, Iatrogenic Disease, Iron, Liver, Magnetic Resonance Imaging, Iron Overload, Hepcidins

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Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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