Finerenone attenuates chronic fibrotic remodeling during the AKI-CKD transition in an ischemia-reperfusion-induced acute kidney injury mouse model

Objective: The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a major cause of poor prognosis in renal injury, and preventing the progression from AKI to CKD has important clinical significance. Finerenone exerts renoprotective effects, however, its role in the AKI-CKD transition remains unclear.Methods: An ischemia-reperfusion (IR)-induced AKI mouse model was established in male C57BL/6 mice by unilateral renal artery clamping combined with contralateral nephrectomy. Finerenone was administered at doses of 10 mg/kg or 15 mg/kg, and renal function, aldosterone levels, podocyte injury, inflammatory responses, and renal fibrosis were evaluated at days 8 and 28 to investigate pathological mechanisms underlying the AKI-CKD transition.Result: Finerenone significantly attenuated IR-induced renal injury and improved renal function during the acute phase and throughout the subsequent AKI–CKD transition. Compared with 10 mg/kg, finerenone at 15 mg/kg more effectively reduced podocyte injury, dampened the inflammatory response, and attenuated renal fibrosis. Mechanistically, finerenone suppressed the p38 phosphorylation and reduced nuclear factor kappa-B (NF-κB) activation during the AKI-CKD transition.Conclusion: Finerenone exerts dose-dependent renoprotective effects during AKI progression and the subsequent AKI–CKD transition, potentially by suppressing podocyte mineralocorticoid receptor overactivation and concomitant reductions in renal inflammation and fibrosis, accompanied by attenuation of p38 phosphorylation and NF-κB activation during the AKI–CKD transition.