Inflammation, cell death, and lncRNAs: unraveling the mechanisms of sepsis-associated acute kidney injury

Sepsis-associated acute kidney injury (SA-AKI) is a common and devastating complication of sepsis and remains a major contributor to morbidity and mortality in critically ill patients. Despite advances in supportive care, effective pharmacological therapies are still lacking, largely due to the complex and multifactorial pathogenesis of SA-AKI. Accumulating evidence indicates that dysregulated inflammation, oxidative stress, and multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, and autophagy—are central drivers of renal tubular and endothelial dysfunction during sepsis. Recent studies have identified long non-coding RNAs (lncRNAs) as critical regulators of these pathogenic processes. Through competing endogenous RNA networks or direct interactions with proteins, lncRNAs modulate inflammatory signaling, oxidative stress responses, and cell fate decisions. This review summarizes current mechanistic insights into lncRNA-mediated regulatory networks in SA-AKI, highlights representative molecular axes defined in experimental models, and discusses the translational potential of lncRNAs as diagnostic biomarkers or therapeutic targets. Importantly, lncRNAs exhibit a context-dependent duality, acting as either pathogenic amplifiers or protective modulators of renal injury, underscoring both their biological complexity and clinical relevance in SA-AKI.