Carbamylated Erythropoietin Improves Angiogenesis and Protects the Kidneys From Ischemia-Reperfusion Injury

Several studies have shown that erythropoietin (EPO) can protect the kidneys from ischemia-reperfusion injury and can raise the hemoglobin (Hb) concentration. Recently, the EPO molecule modified by carbamylation (CEPO) has been identified and was demonstrated to be able to protect several organs without increasing the Hb concentration. We hypothesized that treatment with CEPO would protect the kidneys, partly due to the increased peritubular capillaries. The therapeutic effect of CEPO was evaluated using an endothelial tube formation assay in vitro, and a rat ischemia-reperfusion injury model in vivo. EPO treatment showed the tendency of increased tube formation, while CEPO treatment induced more capillary-like formation than EPO. Ischemia-reperfusion-induced kidneys exhibited characteristic nuclei of apoptosis in tubular epithelial cells with decreased peritubular capillaries, while EPO treatment inhibited tubular apoptosis with preserved endothelial cells. Moreover, CEPO-treated kidneys showed minimal tubular apoptosis with increased peritubular capillary endothelial cells. In conclusion, we identified a new therapeutic approach using CEPO to protect kidneys from ischemia-reperfusion injury by promoting angiogenesis.