Hepcidin for Clinicians

Abstract

Despite the use of erythropoiesis-stimulating agents (ESAs), the anemia of chronic kidney disease (CKD) can be resistant to therapy. Both absolute and functional iron deficiency along with inflammation can contribute to ESA resistance and can be difficult to identify with current-day markers of iron storage. Hepcidin, a small peptide produced by the liver, is a recently discovered key regulator of iron homeostasis. Via regulation of ferroportin, hepcidin inhibits intestinal iron absorption and iron release from macrophages and hepatocytes. Because of its renal elimination and regulation by inflammation, it is possible that progressive renal insufficiency leads to altered hepcidin metabolism, subsequently affecting enteric absorption of iron and the availability of iron stores. Thus, hepcidin likely plays a major role in the anemia of CKD as well as ESA resistance. This article discusses the biologic actions and regulation of hepcidin along with reviewing studies of hepcidin in CKD.

A Phase I/II, Multiple-Dose, Dose-Escalation Study of Siltuximab, an Anti-Interleukin-6 Monoclonal Antibody, in Patients with Advanced Solid Tumors

“…Interestingly, among these patients with hemoglobin response, 88% also showed a decrease in hepcidin, a marker associated with iron regulation. This trend is consistent with the biologic rationale in the literature, in which increased IL-6 levels increases the activity of hepcidin in an inflammatory state (17). Consequently, treatment with the anti-IL-6 siltuximab reduced hepcidin levels with a general trend toward hemoglobin improvement in this study population as well as in an earlier study in B-cell non-Hodgkin's lymphoma, multiple myeloma, or MCD (22).…”

“…Increases in hepcidin result in decreased absorption of iron, resulting in iron-reutilization restricted erythropoiesis and reduced hemoglobin levels (17). Treatment with siltuximab led to a sustained increase in hemoglobin levels in patients with renal cell carcinoma (18) and multicentric Castleman's disease (MCD; ref.…”

Estimating prevalence of functional iron deficiency anaemia in advanced cancer

“…Ferroportin is a transmembrane protein that exports iron [5] and is the only known vertebrate cellular iron exporter [6]. Proinflammatory cytokines, especially interleukin-6 (IL-6) and tumour necrosis factor (TNF) induce hepcidin, a small peptide produced by the liver.…”

Is Hepcidin a Good Marker for Inflammation in Obstructive Sleep Apnea Syndrome (OSAS) Patients?

“…Hepcidin synthesis is induced by iron loading and inflammation and suppressed by iron deficiency, hypoxia and erythropoesis. These complex regulations are not fully understood (35,36), but the induction of hepcidin synthesis by inflammation has been shown to be interleukin-6-dependent (22,37,38). Intermittent hypoxemia occurring in OSAS can stimulate transcription factors such as nuclear factor-κB and increase production of cytokines like IL-6 (39).…”