Finerenone Demonstrates Superior Renoprotective and Anti-Fibrotic Efficacy over Eplerenone in Diabetic Nephropathy Rats

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease worldwide and is characterized by progressive structural remodeling of the renal parenchyma. Although classical steroidal mineralocorticoid receptor (MR) antagonists offer therapeutic benefit, their efficacy in preventing long-term structural kidney damage remains limited. This study evaluated the comparative renal structural preservation conferred by the novel non-steroidal MR antagonist, finerenone, versus the classic steroidal antagonist, eplerenone, in a rat model of DN. Male albino rats were randomized into four distinct experimental groups: Normal control, untreated diabetic control, eplerenone-treated, and finerenone-treated. Following the treatment period, renal tissues were harvested, fixed in neutral buffered formalin, and stained with hematoxylin and eosin. Quantitative and qualitative histopathological microarchitecture evaluations were performed under light microscopy, focusing specifically on glomerular sclerosis, tubular epithelial degeneration, and tubulointerstitial chronic inflammation. Renal sections from the untreated diabetic control group exhibited severe morphological features of advanced nephropathy, including prominent glomerulosclerosis, diffuse tubular epithelial cell vacuolization, marked glomerular hypertrophy, and extensive chronic inflammatory cell infiltration within the interstitium. Eplerenone therapy produced significant structural attenuation, although focal glomerulosclerosis and mild tubular vacuolation remained evident. Conversely, finerenone provided superior parenchymal protection, maintaining near-normal glomerular architecture, intact tubular epithelium, and minimal, isolated interstitial inflammation. In conclusion, non-steroidal MR blockade with finerenone is substantially more effective than eplerenone in mitigating structural remodeling and microvascular damage, proving to be an excellent renoprotective strategy for DN.