doi: 10.1093/ndt/gfm842 Original Article Nonerythropoietic derivative of erythropoietin protects against tubulointerstitial injury in a unilateral ureteral obstruction model

Background. Erythropoietin (EPO), a member of the cy-tokine type I superfamily, acts to increase circulating erythrocytes primarily by preventing apoptosis of ery-throid progenitors, is known to protect tissues and can raise haemoglobin (Hb) concentrations. Recently, a sec-ond receptor for EPO comprising the EPO receptor and β-common receptor has been reported to mediate EPO-induced tissue protection. EPO modified by carbamyla-tion (CEPO) only signals through this second receptor. Accordingly, we hypothesized that treatment with CEPO, which would not increase Hb concentrations, would protect against tubular damage and thereby inhibit tubulointerstitial injuries. Methods.We evaluated therapeutic effects of CEPO using a rat unilateral ureteral obstruction model. Results. CEPO decreased tubular apoptosis and α-smooth muscle actin (αSMA) expression in the absence of poly-cythaemia,while the untreated obstructed kidneys exhibited increased tubular apoptosis with expanded (αSMA) expres-sion.While EPO treatment similarly inhibited tubular apop-tosis and αSMA expression, EPO treatment increased Hb concentrations and induced a wedge-shaped infarction. Conclusion. We established a therapeutic approach using CEPO to protect against tubulointerstitial injury. The thera-peutic value of this approach warrants further attention and preclinical studies