The aim of this study is to clarify the mechanisms underlying this hyporesponse to endogenous EPO, as well as the impact of the long-term treatment of anemia with high doses of rHuEPO associated with antibody mediated erythroid hypoplasia, in a rat model of CKD induced by 5/6 nephrectomy previously characterized by us [29], focusing on iron metabolism, kidney hypoxia, inflammation and fibrosis. The gene discussed is EPO; the disease is anemia.