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

چکیده اصلی

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.

متن کامل اصلی