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Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Open accessAbstract
Background: Anemia, a common complication of chronic kidney disease (CKD), has previously been attributed primarily to decreased production of erythropoietin. More recently, it has become apparent that the etiology of anemia involves several other factors, most notably dysfunctional iron metabolism, mediated via increased hepcidin activity and reduced clearance. Current management of anemia in patients with advanced CKD is based on erythropoiesis-stimulating agents and iron supplementation, along with red blood cell transfusions when necessary; however, safety considerations associated with these therapies highlight the need to pursue alternative treatment options targeting other mechanisms such as hypoxia-inducible factors (HIFs) that act as central regulators of erythropoiesis by coordinating a series of graded hypoxic responses. Summary: This review discusses the discovery of the HIF pathway and its regulation via HIF prolyl hydroxylase enzymes in the context of erythropoiesis and iron metabolism. The rationale for targeting this pathway and the clinical development of HIF prolyl hydroxylase inhibitors are reviewed, with a commentary on the potential implications of this class of agents in CKD anemia management. Key Messages: Pharmacologic activation of the HIF pathway results in a transient pseudo-hypoxic state that stimulates erythropoiesis in CKD patients with anemia. Results from clinical studies of a number of HIF prolyl hydroxylase inhibitors are increasingly available and provide support for the continued evaluation of the risk-benefit ratio of this novel therapeutic approach to the treatment of anemia in CKD.
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Metadata
- Authors
- Locatelli, F., Fishbane, S., Block, G. A., & Macdougall, I. C.
- Venue
- American Journal of Nephrology
- Publisher
- S. Karger AG
- Published
- 2017
- Volume
- 45
- Issue
- 3
- Pages
- 187-199
- ISSN
- 0250-8095 (ISSN-L)
- 1421-9670
- OpenAlex
- W2580449060
- Cited by
- 4,813
- References
- 19
- FWCI
- 270.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- Licence
- creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
- creativecommons.org/licenses/by-nc-nd/4.0/ (tdm)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.