Abstract: Diabetic kidney disease (DKD) is one of the most severe microvascular complications of diabetes mellitus and a leading cause of end-stage renal disease worldwide. Due to the complex pathological mechanisms, conventional therapies are unable to effectively arrest the progression of renal failure. A novel post-translational protein modification lactylation (Kla), is widely involved in the pathogenesis and progression of metabolic diseases. It modulates protein function via lysine residue lactylation triggered by abnormal lactate metabolism, and exerts a critical regulatory role in the initiation and progression of DKD. This review systematically summarizes the molecular mechanisms of lactate accumulation induced by metabolic reprogramming in DKD, as well as the core activation pathways of Kla related to receptors and enzymatic regulation. It elaborates the mechanisms of renal injury mediated by histone and non-histone lactylation, and discusses the potential therapeutic targets and clinical translation prospects of Kla in DKD, so as to provide new theoretical basis and research directions for the diagnosis and treatment of DKD.

Key words: lactylation, diabetic kidney disease, lactic acid metabolism, metabolic reprogramming, renal fibrosis