New Options for Iron Supplementation in Maintenance Hemodialysis Patients

End-stage renal disease results in anemia caused by shortened erythrocyte survival, erythropoietin deficiency, hepcidin-mediated impairment of intestinal absorption and iron release, recurrent blood loss, and impaired responsiveness to erythropoiesis-stimulating agents (ESAs). Iron malabsorption renders oral iron products generally ineffective, and intravenous (IV) iron supplementation is required in most patients receiving maintenance hemodialysis (HD). IV iron is administered at doses far exceeding normal intestinal iron absorption. Moreover, by bypassing physiologic safeguards, indiscriminate use of IV iron overwhelms transferrin, imposing stress on the reticuloendothelial system that can have long-term adverse consequences. Unlike conventional oral iron preparations, ferric citrate has recently been shown to be effective in increasing serum ferritin, hemoglobin, and transferrin saturation values while significantly reducing IV iron and ESA requirements in patients treated with HD. Ferric pyrophosphate citrate is a novel iron salt delivered by dialysate; by directly reaching transferrin, its obviates the need for storing administered iron and increases transferrin saturation without increasing serum ferritin levels. Ferric pyrophosphate citrate trials have demonstrated effective iron delivery and stable hemoglobin levels with significant reductions in ESA and IV iron requirements. To date, the long-term safety of using these routes of iron administration in patients receiving HD has not been compared to IV iron and therefore awaits future investigations.