The effect of frequency of C.E.R.A. administration on the contribution of dietary iron for erythropoiesis

Erythropoiesis-stimulating agents are among the therapeutic options for renal anemia. Under erythropoietic stimulation, the synthesis of hemoglobin requires a large amount of iron, which is supplied both from absorption of dietary iron and the mobilization of stored iron. However, under iron-loading conditions, dietary iron absorption is suppressed via down-regulation of duodenal iron transporters. Because the contribution of dietary iron is essential for erythropoiesis, we aimed to investigate the conditions in which dietary iron is efficiently used for erythropoiesis. To quantify the contribution of dietary iron for erythropoiesis, we labelled dietary iron using the stable iron isotope ⁵⁷Fe, and assessed ⁵⁷Fe-derived hemoglobin synthesis under erythropoietic stimulation by C.E.R.A. (Continuous Erythropoietin Receptor Activator) and iron loading in mice. Our results show that the contribution of dietary iron to erythropoiesis is not changed by different increments of C.E.R.A. dose. However, iron loading suppressed the contribution of dietary iron to erythropoiesis. To confirm these results under conditions mimicking clinical settings, we compared single and intermittent administration of C.E.R.A. in mice under both physiological and iron-loaded conditions, and found that the contribution of dietary iron to erythropoiesis is more strongly affected by body iron status than by erythropoietic stimulation.