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Watanabe, K.* ; Sato, E.* ; Mishima, E. ; Moriya, S.* ; Sakabe, T.* ; Sato, A.* ; Fujiwara, M.* ; Fujimaru, T.* ; Ito, Y.* ; Taki, F.* ; Nagahama, M.* ; Tanaka, K.* ; Kazama, J.J.* ; Nakayama, M.*

Changes in metabolomic profiles induced by switching from an erythropoiesis-stimulating agent to a hypoxia-inducible factor prolyl hydroxylase inhibitor in hemodialysis patients: A pilot study.

Int. J. Mol. Sci. 24:14 (2023)
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Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of medications for managing renal anemia in patients with chronic kidney disease (CKD). In addition to their erythropoietic activity, HIF-PHIs exhibit multifaceted effects on iron and glucose metabolism, mitochondrial metabolism, and angiogenesis through the regulation of a wide range of HIF-responsive gene expressions. However, the systemic biological effects of HIF-PHIs in CKD patients have not been fully explored. In this prospective, single-center study, we comprehensively investigated changes in plasma metabolomic profiles following the switch from an erythropoiesis-stimulating agent (ESA) to an HIF-PHI, daprodustat, in 10 maintenance hemodialysis patients. Plasma metabolites were measured before and three months after the switch from an ESA to an HIF-PHI. Among 106 individual markers detected in plasma, significant changes were found in four compounds (erythrulose, n-butyrylglycine, threonine, and leucine), and notable but non-significant changes were found in another five compounds (inositol, phosphoric acid, lyxose, arabinose, and hydroxylamine). Pathway analysis indicated decreased levels of plasma metabolites, particularly those involved in phosphatidylinositol signaling, ascorbate and aldarate metabolism, and inositol phosphate metabolism. Our results provide detailed insights into the systemic biological effects of HIF-PHIs in hemodialysis patients and are expected to contribute to an evaluation of the potential side effects that may result from long-term use of this class of drugs.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Clinical Trial ; Erythropoiesis-stimulating Agents ; Hemodialysis ; Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitors ; Metabolomic Analysis ; Pleiotropic Effects; Chronic Kidney-disease; Insulin-resistance; Darbepoetin Alpha; Double-blind; Anemia; Phase-3; Myoinositol; Roxadustat; Vadadustat; Efficacy
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1661-6596
e-ISSN 1422-0067
Journal International Journal of Molecular Sciences
Quellenangaben Volume: 24, Issue: 16, Pages: , Article Number: 14 Supplement: ,
Publisher MDPI
Publishing Place Basel
Reviewing status Peer reviewed
Institute(s) Institute of Metabolism and Cell Death (MCD)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-506900-001
Grants
JSPS KAKENHI
This work was supported by JSPS KAKENHI Grant Number 22K11347.
DOI 10.3390/ijms241612752
WOS ID 001055821800001
Scopus ID 85168756751
PubMed ID 37628932
Erfassungsdatum 2023-10-06
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