Imamura, RyoichiIsaka, YoshitakaSandoval, Ruben M.Ichimaru, NaotsuguAbe, ToyofumiOkumi, MasayoshiYazawa, KojiKitamura, HarumiKaimori, JyunyaNonomura, NorioRakugi, HiromiMolitoris, Bruce A.Takahara, Shiro2025-07-012025-07-012012Imamura R, Isaka Y, Sandoval RM, et al. A nonerythropoietic derivative of erythropoietin inhibits tubulointerstitial fibrosis in remnant kidney. Clin Exp Nephrol. 2012;16(6):852-862. doi:10.1007/s10157-012-0647-xhttps://hdl.handle.net/1805/49124Background: The tissue-protective effects of erythropoietin (EPO) have been extensively investigated, and EPO administration can raise the hemoglobin (Hb) concentration. Recently, we reported that carbamylated erythropoietin (CEPO) protected kidneys from ischemia-reperfusion injury as well as EPO. Methods: To investigate the clinical applications of CEPO, we next evaluated the long-term therapeutic effect of CEPO using a tubulointerstitial model rat. We randomized remnant kidney model rats to receive saline, EPO, or CEPO for 8 weeks. Results: CEPO- and EPO-treated rats had improved serum creatinine levels compared with saline-treated remnant kidney model rats, although the Hb level was significantly increased in EPO-treated rats. Two-photon microscopy revealed that EPO/CEPO significantly ameliorated tubular epithelial cell damage assessed by endocytosis. In addition, CEPO or EPO protected endothelial cells with a sustained blood flow rate. EPO or CEPO suppressed the number of TUNEL-positive apoptotic cells with weak αSMA staining. Furthermore, PCR analysis demonstrated that TGF-β and type I collagen expression was attenuated in EPO- or CEPO-treated rats, accompanied by a significant decrease in interstitial fibrosis. Conclusion: We established a long-term therapeutic approach to protect tubulointerstitial injury with CEPO, and thus, the therapeutic value of this approach warrants further attention and preclinical studies.en-USPublisher PolicyCarbamylated erythropoietinRemnant kidneyApoptosisTGF-βArticle