Non-canonical function of erythropoietin and downstream effects of erythropoietin-mediated signaling beyond its role in erythropoiesis

Previous studies indicate the protective effects of ESAs in various disease models, some of which are independent of their erythropoietic feature. However, ESAs contain safety concerns, especially when administered in high dose to fully bring out their favorable effects. ERAs that only activate the non-erythropoietic reactions by EPO seem to be equally beneficial in improving outcome without serious adverse effects, which raises expectations for their further investigation in large clinical trials. So far, non-erythropoietic ERAs are not clinically available yet, and clinicians should understand the risks associated with ESAs upon their usage.