 2. Iron overload - In order to maximize the effect of Epo, the treatment is supplemented by IV injection of iron. This iron may accumulate and cause iron overload in some hemodialyzed patients. Under normal conditions, iron is transported in the blood and enters into cells following binding the plasma protein transferrin. However, when iron content in the plasma exceeds the binding capacity of transferrin, non-transferrin-bound iron NTBI appears. This iron enters cells via alternative pathways, and accumulates in the cytosol, where it participates in chemical reactions Haber-Weiss, Fenton that generate reactive oxygen species ROS. Excess ROS overcomes the protective cellular anti-oxidant mechanisms and becomes cytotoxic. In the erythroid system, excess ROS causes accelerated apoptosis programmed cell death of precursor cells in the bone marrow and a short survival of mature RBCs in the circulation, resulting in chronic anemia. Excess iron and ROS may also damage other cells and lead to malfunctioning of vital organs, such as the heart and liver 2,3. 