[Research advances on the treatment of sepsis-associated acute kidney injury based on mitochondrial dysfunction and...

Sepsis-associated acute kidney injury (SA-AKI) is one of the most common complications of sepsis, characterized by high incidence and mortality. Currently, supportive treatment remains the main approach in clinical practice, lacking specific targeted drugs. Mitochondrial dysfunction and metabolic reprogramming play significant roles in the pathophysiological process of SA-AKI. The kidneys, with their high mitochondrial density and high energy demand, are particularly sensitive to mitochondrial dysfunction. Metabolic reprogramming is another important mechanism for the onset of SA-AKI. When sepsis occurs, the metabolic patterns of kidney cells undergo significant changes, initially shifting from oxidative phosphorylation (OXPHOS) to aerobic glycolysis metabolism, accompanied by inhibition of fatty acid oxidation (FAO). The initial intention is an adaptive protective response of the cells, but persistent metabolic imbalance leads to lipid accumulation and fibrosis, progressing to chronic kidney disease. The two mechanisms interact with each other, jointly causing the occurrence and progression of SA-AKI. This article focuses on these two core mechanisms, systematically reviews the research progress of targeted treatment strategies of SA-AKI, elaborates on the potential application value of mitochondrial protectants and metabolic regulators, deeply analyzes the mechanism of action, in vitro and in vivo experimental evidence, and clinical translation prospects of various drugs, summarizes the current research bottlenecks and looks forward to future development directions, aiming to provide theoretical basis and new research ideas for precise targeted treatment of SA-AKI.