Iron Balance and the Role of Hepcidin in Chronic Kidney Disease

Abstract

The hepatic iron-regulatory hormone hepcidin and its receptor, the cellular iron exporter ferroportin, constitute a feedback-regulated mechanism that maintains adequate plasma concentrations of iron-transferrin for erythropoiesis and other functions, ensures sufficient iron stores, and avoids iron toxicity and iron-dependent microbial pathogenesis. In chronic kidney disease, inflammation and impaired renal clearance increase plasma hepcidin, inhibiting duodenal iron absorption and sequestering iron in macrophages. These effects of hepcidin can cause systemic iron deficiency, decreased availability of iron for erythropoiesis, and resistance to endogenous and exogenous erythropoietin. Together with impaired renal production of erythropoietin, hepcidin-mediated iron restriction contributes to anemia of chronic kidney disease.

Keywords: Anemia; inflammation; iron deficiency; renal failure.

Figure 1

The pathogenesis of iron dysregulation in chronic kidney disease (CKD). The diagram shows the hepcidin-stimulatory effects of inflammation and iron treatment, the hepcidin-increasing effect of decreased glomerular filtration rate, and the opposing suppressive effects of erythropoietin and erythroferrone on hepcidin production. Plasma hepcidin concentrations are usually high, decreasing ferroportin on cell membranes, and thus inhibiting duodenal iron absorption and diminishing iron availability for erythropoiesis. IL, interleukin.