Hypoxia Inducible Factors Proly-Hydroxylase Inhibitors: A Novel Treatment of CKD Patient Anemia

A special issue of Kidney and Dialysis (ISSN 2673-8236).

Deadline for manuscript submissions: 31 December 2024 | Viewed by 3391

Special Issue Editors


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Guest Editor
Department of Nephrology and Dialysis, Alessando Manzoni Hospital, Lecco, Italy
Interests: CKD; proteinuria; hypertension; anemia; ESAS; iron
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Guest Editor
Department of Nephrology and Dialysis, ASST Lariana, 22100 Como, Italy
Interests: anemia; chronic kidney disease; glomerulonephritis; diabetic nephropathy hypoxia indicibile factor; iron

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Guest Editor
1. Unit of Nephrology and Dialysis, Department of Internal Medicine, ICS Maugeri S.p.A. SB, University of Pavia, 27100 Pavia, Italy
2. Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
Interests: CKD and complications; dialysis; glomerular disease; AKI

Special Issue Information

Dear Colleagues,

The pathogenesis of anemia in chronic kidney disease (CKD) patients includes decreased production of erythropoietin (EPO), often associated with iron deficiency; its current management includes iron supplementation, erythropoiesis-stimulating agents (ESAs), and eventually red blood cell transfusion. The introduction of ESAs in the late 1980s revolutionized the treatment of anemia in CKD and resulted in a significant decline in the need for blood transfusions. However, these agents are associated with increased rates of hypertension, seizures, thrombosis, cardiovascular (CV) events, and functional iron deficiency when aimed at normalizing the hemoglobin (Hb) plasma level. Moreover, resistance to ESAs has been observed in a certain proportion of patients, mainly due to chronic inflammation producing cytokines.

A novel class of therapeutic agents for the treatment of anemia in patients with CKD was developed by inhibiting the enzymes that control hypoxia-inducible factors (HIFs), a family of oxygen-sensitive proteins that regulate the cellular transcriptional response to hypoxia. HIFs are controlled by a family of prolyl hydroxylase enzymes, important for maintaining the relationship between oxygen availability and HIF-α expression. These HIF proteins, known as ‘oxygen sensors’ due to their dependency upon oxygen as a direct substrate, are called PHD1, PHD2, and PHD3 based on their distinctive prolyl-4-hydroxylase domains (PHD). They belong to a larger family of proteins (60+ members in humans) whose role, in addition to ‘sensing’ changes in cellular oxygen, includes collagen synthesis and fatty acid metabolism.

Phase 3 trials recently became available for drugs of this class.

The aim of this Special Issue is to report and discuss the efficacy and safety and clinical impact of these drugs, according to the present available data with the help of major experts in the field of treatment of anemia in CKD patients.

Prof. Dr. Francesco Locatelli
Dr. Lucia Del Vecchio
Dr. Ciro Esposito
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Kidney and Dialysis is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • chronic kidney disease
  • CKD
  • anemia
  • iron deficiency
  • red blood cell
  • hypertension
  • seizures
  • thrombosis
  • cardiovascular
  • hypoxia-inducible factors
  • HIFs
  • hypoxia
  • HIF-HPI
  • nephrology

Published Papers (1 paper)

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8 pages, 242 KiB  
Perspective
Is HIF-PHI the Answer to Tackle ESA Hyporesponsiveness in the Elderly?
by Henry H. L. Wu, Rajkumar Chinnadurai and Robert J. Walker
Kidney Dial. 2022, 2(3), 446-453; https://doi.org/10.3390/kidneydial2030040 - 04 Aug 2022
Cited by 1 | Viewed by 2695
Abstract
Anemia in chronic kidney disease (CKD) has become an important clinical issue with the increased prevalence of elderly patients living with CKD progressing to kidney failure. The causes of anemia in elderly individuals tend to be multifactorial, exacerbated by the physiological effects of [...] Read more.
Anemia in chronic kidney disease (CKD) has become an important clinical issue with the increased prevalence of elderly patients living with CKD progressing to kidney failure. The causes of anemia in elderly individuals tend to be multifactorial, exacerbated by the physiological effects of aging, frailty and declining kidney function. Erythropoiesis-stimulating agents (ESAs) are the conventional therapeutic option for anemia in CKD. However, ESA hyporesponsiveness is a commonly observed issue in clinical practice and an issue that is more challenging to resolve in elderly patients living with frailty, kidney disease, and multi-morbidities. Following the emergence of oral hypoxia-induced factor prolyl-hydroxylase inhibitors (HIF-PHI) in recent years, there is discussion on whether it is a solution to the conundrum of ESA hyporesponsiveness, as HIF-PHI treats anemia via an alternative physiological pathway. There remains uncertainty on the suitability of HIF-PHI use in elderly patients, given a lack of data on its safety over long-term follow-up for the elderly population. Further study is needed to provide answers, considering the clinical significance of this issue within a public-health scale. Full article
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