Renal anemia: from erythropoietin deficiency to erythropoietin resistance

Renal anemia is one of the core complications of chronic kidney disease (CKD) and is closely associated with poor patient prognosis. Renal interstitial fibrosis or impaired oxygen sensing leads to insufficient erythropoietin (EPO) production, which constitutes the fundamental mechanism initiating renal anemia. On this basis, multiple pathological factors—including the inflammatory microenvironment in CKD, iron deficiency, and mineral and bone disorders—synergistically induce EPO resistance, further exacerbating anemia and diminishing the response to existing therapies. Currently, the treatment of renal anemia has moved beyond simple EPO replacement and is progressively shifting toward a dual strategy that emphasizes both correction of EPO resistance and enhancement of drug responsiveness. This article summarizes the molecular network through which insufficient EPO synthesis and EPO resistance synergistically aggravate renal anemia, systematically reviews the pharmacological basis, limitations, and safety risks of current drug therapies, and discusses future research directions and potential therapeutic targets in this field.