Targeting ferroptosis alleviates burn-induced acute kidney injury

Abstract Acute kidney injury (AKI) is one of the most common and lethal complications in severely burned patients. Its clinical management has long been challenged by a dilemma: high incidence and mortality rates coexist with the absence of targeted therapies, largely due to an incomplete understanding of the molecular networks that drive “burn-to-kidney” injury. Here, we report the renal proteomic landscape of burn-induced AKI and identify ferroptosis as a critical mechanism underlying its pathogenesis. Using a murine model of burn-induced AKI that recapitulates elevated serum creatinine and urea levels as well as tubular necrosis, quantitative proteomics revealed widespread protein changes, with upregulated proteins enriched in iron transport and ferroptosis‑related pathways. Specifically, ferroptosis-associated proteins ACSL4, FTH1, FTL1, and MT1/2 were upregulated and highly correlated with the tubular injury marker KIM1. Importantly, pharmacological inhibition of ferroptosis effectively attenuated burn-induced AKI, as evidenced by reduced serum biomarkers, decreased tubular necrosis, and improved survival. Together, these findings unveil a burn‑specific ferroptosis‑related molecular signature and provide a rationale for targeted intervention in burn‑induced AKI.