Abstract
Introduction: One of the most common causes of acute kidney injury (AKI) is renal ischemia/reperfusion (IR). Mineralocorticoid receptor (MR) antagonism has shown beneficial effects against renal IR consequences. The potential benefit of novel non-steroidal MR antagonists such as finerenone has not been explored. Objective: Evaluate the efficacy of finerenone to prevent the acute and chronic consequences of ischemic AKI. Methods: For the acute study (24 hours), 18 rats were divided in: sham, rats subjected to bilateral renal ischemia of 25 min and rats that received three doses of finerenone at -48 h, -24 h and -1 h before the ischemia. For the chronic study (4 months), 21 rats were divided in: sham, rats with 45 min of bilateral ischemia and rats treated with Finerenone at day -2, -1 and 1h before IR. The left kidney was used for histology and the right kidney for molecular analysis. Results: After 24 h of reperfusion, the untreated IR rats presented a 3-fold increase in plasma creatinine, accompanied by 40% of tubules presenting cell detachment and casts. Kim-1 and NGAL mRNA levels were induced by 30-fold. In contrast, the rats that received finerenone presented normal creatinine and significantly fewer injured tubules (11%) and a less pronounced induction of kim-1 and NGAL (8-fold). After 4 months, the untreated IR rats developed chronic kidney disease (CKD), evidenced by kidney dysfunction, increased proteinuria (121.6 vs. 14.3 mg/24h in sham) and renal vascular resistance (16.8 vs. 11.4 mmHg/mL in sham). Tubular dilation, extensive tubule-interstitial fibrosis and an increase in kidney TGF-β and Collagen-I mRNA levels also characterized CKD. The transition from AKI to CKD was fully prevented by finerenone administration at the time of IR. Conclusion: Altogether, our data shows that finerenone is able to prevent AKI induced by IR as well as the chronic and progressive deterioration of kidney function and structure.
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