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Int. J. Mol. Sci. 2018, 19(2), 389; https://doi.org/10.3390/ijms19020389

Hypoxia-Inducible Factor and Its Role in the Management of Anemia in Chronic Kidney Disease

Division of Nephrology and Hypertension, Rutgers-New Jersey Medical School, University Hospital, 185 South Orange Avenue, I512, Newark, NJ 07103, USA
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Received: 7 December 2017 / Revised: 4 January 2018 / Accepted: 8 January 2018 / Published: 29 January 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Hypoxia-inducible factor (HIF) plays a crucial role in the response to hypoxia at the cellular, tissue, and organism level. New agents under development to pharmacologically manipulate HIF may provide new and exciting possibilities in the treatment of anemia of chronic kidney disease (CKD) as well as in multiple other disease states involving ischemia–reperfusion injury. This article provides an overview of recent studies describing current standards of care for patients with anemia in CKD and associated clinical issues, and those supporting the clinical potential for targeting HIF stabilization with HIF prolyl-hydroxylase inhibitors (HIF-PHI) in these patients. Additionally, articles reporting the clinical potential for HIF-PHIs in ‘other’ putative therapeutic areas, the tissue and intracellular distribution of HIF- and prolyl-hydroxylase domain (PHD) isoforms, and HIF isoforms targeted by the different PHDs, were identified. There is increasing uncertainty regarding the optimal treatment for anemia of CKD with poorer outcomes associated with treatment to higher hemoglobin targets, and the increasing use of iron and consequent risk of iron imbalance. Attainment and maintenance of more physiologic erythropoietin levels associated with HIF stabilization may improve the management of patients resistant to treatment with erythropoiesis-stimulating agents and improve outcomes at higher hemoglobin targets. View Full-Text
Keywords: anemia; chronic kidney disease; hypoxia-inducible factor; prolyl-hydroxylase; erythropoiesis-stimulating agent anemia; chronic kidney disease; hypoxia-inducible factor; prolyl-hydroxylase; erythropoiesis-stimulating agent
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Kaplan, J.M.; Sharma, N.; Dikdan, S. Hypoxia-Inducible Factor and Its Role in the Management of Anemia in Chronic Kidney Disease. Int. J. Mol. Sci. 2018, 19, 389.

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