Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review)

Diabetic kidney disease (DKD), a predominant contributor to end‑stage renal disease, is distinguished by its intricate pathogenesis and constrained therapeutic interventions. The present review discusses the role of glycolytic flux‑mediated protein lactylation, an emerging epigenetic modification, in the progression of DKD. Under conditions of hyperglycemia and hypoxia, renal cells undergo a metabolic shift towards glycolysis, resulting in the accumulation of lactate. Beyond its role as a metabolic byproduct, lactate functions as a signaling molecule that facilitates the lactylation of both histones and non‑histone proteins. The present review discusses how lactylation has been implicated in key pathological mechanisms in DKD, including ferroptosis, dysregulated autophagy and fibrosis. The interplay between lactylation and other posttranslational modifications is also discussed, along with the therapeutic potential of targeting the glycolysis‑lactylation axis. By highlighting this metabolic‑epigenetic crosstalk, the present review proposes a conceptual framework that may inform the development of diagnostic and therapeutic strategies targeting lactylation in DKD.