What is hepcidin and why is it important to nephrologists?
Hepcidin is a 25-amino acid peptide (see left) secreted by the liver which seems to be the “master regulator” of iron metabolism. It works by binding to the iron channel ferroportin, which is located on the basolateral surface of gut enterocytes and the plasma membrane of reticuloendothelial cells, and degrading ferroportin, thereby shutting off iron transport out of these cells.
In ESRD, hepcidin levels are elevated–probably in part because hepcidin is cleared by the kidneys, and perhaps also because of increased hepcidin expression in the presence of certain inflammatory cytokines. As a result, iron uptake from the gut is diminished (iron can get into the enterocyte via an apical Fe transporter, but can’t get out the basolateral surface because it needs ferroportin), and iron is trapped inside of reticuloendothelial cells. This latter phenomenon, “an inability to mobilize iron stores”, has long been known to play an important role in the anemia of chronic disease.
One might imagine that hepcidin inhibitors might be a successful pharmacologic intervention for CKD or ESRD patients with anemia.