Darbepoetin-α treatment enhances glomerular regenerative process in the Thy-1 glomerulonephritis model

Canadillas S, Ortega R, Estepa JC, Egea J, Gonzalez-Menchen A, Perez-Seoane C, Lopez-Andreu M, Ramirez R, Tetta C, Rodriguez M, Martin-Malo A, Aljama P. Darbepoetin-alpha treatment enhances glomerular regenerative process in the Thy-1 glomerulonephritis model. Am J Physiol Renal Physiol 299: F1278-F1287, 2010. First published September 8, 2010; doi:10.1152/ajprenal.00343.2009.-Recent studies have demonstrated that erythropoietin (EPO) and its analogs induce cytoprotective effects on many nonerythroid cells. In this study, we examined whether darbepoetin-alpha might prevent glomerular lesions in the Thy-1.1 model of glomerulonephritis (Thy-1-GN). GN was induced in Wistar rats by a single injection of monoclonal anti-Thy-1.1 antibody. Rats were killed at 24 h, 72 h, 7 days, 10 days, or 15 days after antibody injection. Kidneys were removed for histological analysis, and proteinuria was measured. Because at day 7 the maximal degree of renal damage and proteinuria was found, the effect of darbepoetin-alpha was tested at day 7 and two different protocols of administration were used; After anti-Thy-1.1 injection, rats received two doses of darbepoetin-alpha or vehicle at days 0 and 4 or at days 4 and 6. At day 7, proteinuria, plasma creatinine concentration, and renal morphology analysis were performed. Also, alpha-actin, desmin, caspase-3, and Ki67 protein expression were evaluated by immunohistochemistry. Our results showed that in both protocols of administration, darbepoetin-alpha treatment decreased proteinuria in Thy-1-GN rats and this effect correlated with the improvement in renal morphology. Glomerular lesions, alpha-actin, and caspase-3 protein expression, observed in most glomeruli of Thy-1-GN rats, were significantly reduced in darbepoetin-alpha-treated rats, while cell proliferation was significantly enhanced. The results indicate that darbepoetin-alpha treatment promotes glomerular recovery.