Title:Role of Hepcidin-25 in Chronic Kidney Disease: Anemia and Beyond
Volume: 24
Issue: 14
Author(s): Norishi Ueda* Kazuya Takasawa
Affiliation:
- Department of Pediatrics, Public Central Hospital of Matto Ishikawa, 3-8 Kuramitsu, Hakusan, 924-8588 Ishikawa,Japan
Keywords:
Anemia, erythropoiesis, ferritin, hepcidin-25, hypoxia, inflammation, iron, kidney injury.
Abstract: Iron is an essential element for all living organisms, but produces toxic oxidants.
Thus, iron homeostasis is tightly regulated in mammals. Hepcidin-25 (hepcidin) has emerged
as a molecule that regulates iron metabolism. Binding of hepcidin to its receptor, ferroportin,
inhibits intestinal iron absorption and iron efflux from hepatocytes and macrophages. Decreased
hepcidin enhances iron absorption and efflux. Hepcidin could be predictive of iron
status and the response to iron supplementation or erythropoietin-stimulating agents. Monitoring
hepcidin is helpful for the management of anemia. Thus, it is urgent to obtain normal reference
values in a large population of healthy subjects and to standardize various hepcidin assays,
which enables to compare the data measured by different methods. Anemia is an important
and common problem associated with chronic kidney disease (CKD), which is caused by
erythropoietin deficiency, iron-restricted erythropoiesis, inflammation, hypoxia, vitamin D
deficiency, hyperparathyroidism, and obesity. Anemia causes poor quality of life, progression
of CKD, increased risk of cardiovascular events, and mortality. Besides its role in anemia, recent
evidence suggests that hepcidin-25 plays a role in the pathogenesis and progression of
kidney injury via modulation of iron-mediated oxidant injury. Despite accumulating experimental
data, information about clinical significance of hepcidin-25 for anemia and kidney injury
in CKD patients is scarce, especially in children. This review summarizes the current
knowledge of the role of hepcidin-25 in the regulation of anemia and kidney injury in children
and adults with CKD. Strategy for modulating hepcidin-25 to prevent anemia and kidney injury
associated with CKD is also discussed.