The mineralocorticoid receptor antagonist eplerenone reduces renal interstitial fibrosis after long-term cyclosporine treatment in rat: antagonizing cyclosporine nephrotoxicity

Chronic cyclosporine-(CsA)-mediated loss of kidney function is a major clinical problem in organ transplantation. We hypothesized that the mineralocorticoid receptor antagonist eplerenone (EPL) prevents chronic CsA-induced renal interstitial volume increase, tubule loss, and functional impairment in a rat model. Sprague-Dawley rats received CsA alone (15 mg/kg/d p.o.), CsA and EPL (approximately 100 mg/kg/day p.o.) or vehicle (control) for 12 weeks. At 11 weeks, chronic indwelling arterial and venous catheters were implanted for continuous measurements of arterial blood pressure (BP) and GFR (inulin clearance) in conscious, freely moving animals. Plasma was sampled for analysis and kidney tissue was fixed for quantitative stereological analyses. Compared to controls, CsA-treatment reduced relative tubular volume (0.73 ± 0.03 vs. 0.85 ± 0.01, p