Erythropoietin enhances recovery after cisplatin-induced acute renal failure in the rat

Background. Erythropoietin (Epo) is a growth factor whose synthesis mainly takes place in the kidney. Epo has been shown to support the growth not onl y of erythroid progenitor cells but also of certain other cell types. We at tempted to establish whether Epo enhances the recovery from acute renal fai lure induced by cisplatin. Methods. Sprague-Dawley rats were randomized into three groups. In the cisp latin group, animals received one intraperitoneal injection of cisplatin (6 mg/kg) and a daily injection of placebo for 9 days. In the cisplatin+Epo g roup, animals received intraperitoneal cisplatin and a daily injection of E po (100 IU/kg) for 9 days. In the control group, animals received both plac ebo preparations alone. Para-aminohippuric acid and inulin clearances were determined after 4 and 9 days to evaluate renal blood flow and glomerular f iltration rate. In addition, light microscopy and immunohistochemistry exam inations were performed, and in situ proliferating cell nuclear antigen (PC NA) staining was done to estimate the degree of renal tubular cell regenera tive activity. The potential role of epithelial growth factor (EGF) was eva luated by semi-quantitative assessment of EGF immunostaining. Results. Renal blood flow and glomerular filtration rate decreased signific antly in cisplatin and cisplatin+Epo groups versus control group at day 4. However, at day 9, they both were significantly greater in cisplatin+Epo-tr eated animals than in rats that had received cisplatin alone. Tubular cell regeneration was significantly enhanced at day 4 in cisplatin+Epo group, co mpared with cisplatin and control groups respectively, EGF immunostaining w as not significantly different between the three groups. Conclusion. Epo significantly enhanced the rate of recovery from acute rena l failure induced by cisplatin. PCNA staining indicated that Epo might act directly via stimulation of tubular cell regeneration.