Nephrol Dial Transplant (2001) 16: 932-938
© 2001 European Renal Association-European Dialysis and Transplant Association
Erythropoietin enhances recovery after cisplatin-induced acute renal failure in the rat
1 Department of Nephrology, 3 Biochemistry and 4 Pathology, Pitié-Salpêtrière Hospital, Paris, France, 2 INSERM U423, Necker-Enfants Malades Hospital, Paris, and 5 Laboratoire de Biochimie, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France
Background. Erythropoietin (Epo) is a growth factor whose synthesis mainly takes place in the kidney. Epo has been shown to support the growth not only of erythroid progenitor cells but also of certain other cell types. We attempted to establish whether Epo enhances the recovery from acute renal failure induced by cisplatin.
Methods. Sprague-Dawley rats were randomized into three groups. In the cisplatin group, animals received one intraperitoneal injection of cisplatin (6 mg/kg) and a daily injection of placebo for 9 days. In the cisplatin+Epo group, animals received intrapertoneal cisplatin and a daily injection of Epo (100 IU/kg) for 9 days. In the control group, animals received both placebo preparations alone. Para-aminohippuric acid and inulin clearances were determined after 4 and 9 days to evaluate renal blood flow and glomerular filtration rate. In addition, light microscopy and immunohistochemistry examinations were performed, and in situ proliferating cell nuclear antigen (PCNA) staining was done to estimate the degree of renal tubular cell regenerative activity. The potential role of epithelial growth factor (EGF) was evaluated by semi-quantitative assessment of EGF immunostaining.
Results. Renal blood flow and glomerular filtration rate decreased significantly in cisplatin and cisplatin+Epo groups versus control group at day 4. However, at day 9, they both were significantly greater in cisplatin+Epo-treated animals than in rats that had received cisplatin alone. Tubular cell regeneration was significantly enhanced at day 4 in cisplatin+Epo group, compared with cisplatin and control groups respectively. EGF immunostaining was not significantly different between the three groups.
Conclusion. Epo significantly enhanced the rate of recovery from acute renal failure induced by cisplatin. PCNA staining indicated that Epo might act directly via stimulation of tubular cell regeneration.
Keywords: acute renal failure; chemotherapy; cisplatin; erythropoietin; tubular necrosis
Correspondence and offprint requests to: Corinne Bagnis, Massachusetts General Hospital East, Department of Nephrology, Renal Unit 8th floor, 149 13th Street, Charlestown, MA 02129, USA.
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