Intermittent Fasting Protects Against the Progression from Acute Kidney Injury to Chronic Kidney Disease

Acute kidney injury (AKI) is a major but often underestimated risk factor for the development of chronic kidney disease (CKD). Exploring innovative approaches to prevent this progression is critical. Intermittent fasting (IF), recognized for its metabolic and anti-inflammatory benefits, may offer protective effects in this context. Using a unilateral ischemia-reperfusion injury (UIRI) model in male C57BL/6 mice, we evaluated the impact of IF on tubulointerstitial fibrosis and tubular epithelial-mesenchymal transition (EMT) over 8 weeks. Mice in the IF group followed a 5:2 regimen, fasting for 24 h twice weekly. Four groups were studied: control, IF, UIRI, and IF + UIRI. The UIRI group exhibited increased fibrosis and EMT, both of which were significantly attenuated in the IF + UIRI group. IF also reduced levels of TGF-β1, phosphorylated NF-κB p65, inflammatory cytokines, and F4/80-positive macrophages, along with markers of oxidative stress. These findings highlight IF's ability to mitigate fibrosis and EMT through reductions in inflammation and oxidative stress during AKI-to-CKD progression. Our study suggests that IF may serve as a promising dietary strategy to prevent AKI from advancing into CKD.