Role of Zinc and Copper in Erythropoiesis in Patients on Hemodialysis

Plasma zinc concentrations are decreased in patients on hemodialysis; zinc supplementation increases hemoglobin levels and reduces erythropoietin-stimulating agent treatments. However, inappropriate zinc supplementation causes copper deficiency. This review discusses the roles of zinc and copper throughout erythropoiesis; it also describes erythropoiesis-stimulating nutritional therapy that avoids copper deficiency, while providing safe zinc supplementation. In early erythropoiesis, erythropoietin regulates erythrocyte precursor proliferation and survival via zinc finger transcription factors. Mature blood cell formation and functional activation are regulated by zinc-mediated hormones, vitamins, and growth peptides. Zinc antagonizes the uptake of divalent cations (e.g., iron and copper) in erythrocyte precursors. Copper is required for iron transfer from cells to blood, ensuring dietary iron absorption and systemic iron distribution. In patients with copper deficiency, copper supplementation is initially performed, followed by zinc supplementation to manage hypozincemia. Serum zinc and copper measurements are needed at 2- to 3-month intervals during zinc supplementation to prevent copper deficiency.