Cited by 345Erythropoietin and Anemia TreatmentHemoglobin structure and functionBiosimilars and Bioanalytical Methods

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Inhibition of Prolyl Hydroxylases Increases Erythropoietin Production in ESRD

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Bernhardt, Wanja M., Wiesener, Michael S., Scigalla, Paul, Chou, James, Schmieder, Roland E., Günzler, Volkmar, Eckardt, Kai-Uwe·2010·Journal of the American Society of Nephrology

DOI 10.1681/asn.2010010116PMC PMC3014028

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Abstract

The reasons for inadequate production of erythropoietin (EPO) in patients with ESRD are poorly understood. A better understanding of EPO regulation, namely oxygen-dependent hydroxylation of the hypoxia-inducible transcription factor (HIF), may enable targeted pharmacological intervention. Here, we tested the ability of fibrotic kidneys and extrarenal tissues to produce EPO. In this phase 1 study, we used an orally active prolyl-hydroxylase inhibitor, FG-2216, to stabilize HIF independent of oxygen availability in 12 hemodialysis (HD) patients, six of whom were anephric, and in six healthy volunteers. FG-2216 increased plasma EPO levels 30.8-fold in HD patients with kidneys, 14.5-fold in anephric HD patients, and 12.7-fold in healthy volunteers. These data demonstrate that pharmacologic manipulation of the HIF system can stimulate endogenous EPO production. Furthermore, the data indicate that deranged oxygen sensing--not a loss of EPO production capacity--causes renal anemia.

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Authors: Bernhardt, W. M., Wiesener, M. S., Scigalla, P., Chou, J., Schmieder, R. E., Günzler, V., & Eckardt, K.-U.
Affiliations: Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
ORCID: Bernhardt, Wanja M.
Wiesener, Michael S.
Schmieder, Roland E.
Eckardt, Kai-Uwe
Venue: Journal of the American Society of Nephrology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2010-12
Volume: 21
Issue: 12
Pages: 2151-2156
ISSN: 1046-6673 (ISSN-L)
DOI: 10.1681/asn.2010010116
PMC: PMC3014028
OpenAlex: W2136732413
Cited by: 340
References: 33
Citations by year: 2026: 7 · 2025: 12 · 2024: 8 · 2023: 20 · 2022: 23 · 2021: 31 · 2020: 16 · 2019: 13 · 2018: 18 · 2017: 25 · 2016: 28 · 2015: 30 · 2014: 22 · 2013: 34 · 2012: 28
FWCI: 17.26
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of the American Society of Nephrology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: FibroGen
Topics: Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
Keywords: erythropoietin, prolyl hydroxylase inhibitors, hypoxia-inducible factor, end-stage renal disease, anemia of chronic kidney disease, hemodialysis, oxygen sensing, anephric patients
MeSH terms: Administration, Oral, Adult, Aged, Aged, 80 and over, Anemia, Erythropoietin, Female, Follow-Up Studies, Renal Dialysis, Humans, Kidney Failure, Chronic, Male, Middle Aged, Nephrectomy, Procollagen-Proline Dioxygenase, Reference Values, Treatment Outcome, Risk Assessment, Hypoxia-Inducible Factor 1, alpha Subunit

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Inhibition of Prolyl Hydroxylases Increases Erythropoietin Production in ESRD

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