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Four Cases of Serum Copper Excess in Patients with Renal Anemia Receiving a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor: A Possible Safety Concern

Authors :
Hironori Nakamura
Shigekazu Kurihara
Mariko Anayama
Yasushi Makino
Masaki Nagasawa
Source :
Case Reports in Nephrology and Dialysis, Vol 12, Iss 2, Pp 124-131 (2022)
Publication Year :
2022
Publisher :
Karger Publishers, 2022.

Abstract

Copper is an indispensable trace metal element and is mainly absorbed in the stomach and small intestine and excreted into the bile. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have emerged as a novel approach for renal anemia management. Many intestinal genes, including divalent metal transporter 1, duodenal cytochrome B, and copper transporter ATPase7A, related to iron absorption are transactivated by HlF-α, during iron deficiency. We first report 4 cases of patients with renal anemia who showed excess in serum copper level during roxadustat or daprodustat treatment, which were decreased to the normal level after discontinuing HIF-PHIs and changing the drug to darbepoetin alfa, suggesting that HIF-PHI is associated with serum copper excess. HIF-PHI modulates iron metabolism, such as iron absorption, sequestration, and mobilization, and may increase serum copper levels by increasing copper absorption and/or redistribution of copper in tissues. Therefore, it is urgent to examine the correlation between HIF-PHI use and serum copper levels because copper excess might be involved in several acute or chronic adverse events.

Details

Language :
English
ISSN :
22969705
Volume :
12
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Case Reports in Nephrology and Dialysis
Publication Type :
Academic Journal
Accession number :
edsdoj.6ea6f426c2ea4defb30f926fbdf0b6ee
Document Type :
article
Full Text :
https://doi.org/10.1159/000525735