Cited by 315Erythropoietin and Anemia TreatmentIron Metabolism and DisordersHemoglobin structure and function

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Anaemia in kidney disease: harnessing hypoxia responses for therapy

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Koury, Mark J., Haase, Volker H.·2015·Nature Reviews Nephrology

DOI 10.1038/nrneph.2015.82PMC PMC4497972

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Abstract

Improved understanding of the oxygen-dependent regulation of erythropoiesis has provided new insights into the pathogenesis of anaemia associated with renal failure and has led to the development of novel therapeutic agents for its treatment. Hypoxia-inducible factor (HIF)-2 is a key regulator of erythropoiesis and iron metabolism. HIF-2 is activated by hypoxic conditions and controls the production of erythropoietin by renal peritubular interstitial fibroblast-like cells and hepatocytes. In anaemia associated with renal disease, erythropoiesis is suppressed due to inadequate erythropoietin production in the kidney, inflammation and iron deficiency; however, pharmacologic agents that activate the HIF axis could provide a physiologic approach to the treatment of renal anaemia by mimicking hypoxia responses that coordinate erythropoiesis with iron metabolism. This Review discusses the functional inter-relationships between erythropoietin, iron and inflammatory mediators under physiologic conditions and in relation to the pathogenesis of renal anaemia, as well as recent insights into the molecular and cellular basis of erythropoietin production in the kidney. It furthermore provides a detailed overview of current clinical experience with pharmacologic activators of HIF signalling as a novel comprehensive and physiologic approach to the treatment of anaemia.

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Authors: Koury, M. J., & Haase, V. H.
Affiliations: Vanderbilt University Medical Center (US)
Corresponding author: Haase, Volker H.
ORCID: Koury, Mark J.
Haase, Volker H.
Venue: Nature Reviews Nephrology
Publisher: Springer Science and Business Media LLC
Published: 2015-06-09
Volume: 11
Issue: 7
Pages: 394-410
ISSN: 1745-8323 (ISSN-L)
1759-5061
1759-507X
DOI: 10.1038/nrneph.2015.82
PMC: PMC4497972
OpenAlex: W1893364029
Cited by: 313
References: 239
Citations by year: 2026: 20 · 2025: 28 · 2024: 26 · 2023: 39 · 2022: 45 · 2021: 36 · 2020: 31 · 2019: 20 · 2018: 22 · 2017: 20 · 2016: 20 · 2015: 5
FWCI: 3.34
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Nephrology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Veterans Affairs (I01 BX002348)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080821, R01DK101791, R01DK081646)
Topics: Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
Keywords: anemia of chronic kidney disease, erythropoiesis, erythropoietin, hypoxia-inducible factor, HIF-2, iron metabolism, inflammation, iron deficiency, renal failure, hepatocytes, oxygen sensing
MeSH terms: Endothelial PAS Domain-Containing Protein 1, Anemia, Erythropoiesis, Humans, Signal Transduction, Cell Hypoxia, Renal Insufficiency, Chronic, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1

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Anaemia in kidney disease: harnessing hypoxia responses for therapy

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