Should we reconsider iron administration based on prevailing ferritin and hepcidin concentrations?
Takeshi Nakanishi,corresponding author Takahiro Kuragano, Shoji Kaibe, Yasuyuki Nagasawa, and Yukiko Hasuike
he discovery of hepcidin has profoundly changed our understanding of the place of FID in renal anemia therapy. Hepcidin reduces the abundance of iron transport proteins which facilitate iron absorption from the gut and iron mobilization from macrophages. Serum hepcidin is mainly modulated by iron stores, as is serum ferritin. High hepcidin or ferritin levels block intestinal iron absorption and iron recycling in macrophages and decrease iron availability for erythropoiesis, leading to FID. Iron administration, especially IVFe, increases hepcidin levels and concomitantly inhibits iron supply to erythroid cells. This in turn could lead to a vicious circle, exacerbating FID and increasing iron demand. Therefore, physicians should be cautious with unrestricted IVFe to chronic kidney disease patients with FID.
Recent studies on the mechanisms involved in iron metabolism have revealed that hepcidin is a master regulator of systemic iron availability [6, 7]. To maintain iron homeostasis, hepcidin tightly controls duodenal iron absorption and iron recycling from senescent erythrocytes by tissue macrophages. Hepcidin is the principal hormone responsible for the physiological regulation of iron balance as well as its control in a variety of pathologic conditions, including the anemia of chronic disease (ACD).
In this review, we address the mechanisms whereby pharmacological iron supplementation, especially via the IV route, may reduce the body’s capacity to absorb iron from the gut and to reutilize iron from endogenous sources , with particular focus on the importance of hepcidin in this process.