We are investigating the expression and function of hepcidin, ferroportin, and other related iron-regulatory proteins that would lead to identification of ESA hyporesponder patients and eventually to better outcomes.
Our studies are based on a well-characterized surgical mouse model of CKD. Preliminary data have shown that anemia of CKD resulted in lower hepcidin expression. Hepcidin expression decreased even further as iron requirements increased after reversal of the anemia by erythropoietin (Epo).
As expected, the further hepcidin downregulation seen in the Epo-treated mice facilitated the release of stored RE iron necessary to sustain Epo-stimulated erythropoiesis and was manifested by a lower non-heme tissue iron. These findings suggest that anemia in this CKD model is characterized by a lower hepcidin expression but that full hepcidin downregulation, which will result in RE iron release, is necessary for Epo response.
We speculate that a diminished hepcidin expression in anemia of CKD is necessary for an Epo response in humans as well. The downregulation of hepcidin facilitates the release of RE iron necessary to support the augmented erythropoiesis; any alteration of this hepcidin response could have enormous clinical and economic implications in the management of anemia of CKD.