Lele Sun,1,2, Yuanyuan Yang,1,2, Wenyi Pan,1,2, Chenghua Zhang,2 Jiawei Lu,2 Shaowen Guo,1,2 Ying Zhu,3 Meifeng Zhu2 1Department of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Peopleâs Republic of China; 2Department of Nephrology, Changzhou Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou, Jiangsu, Peopleâs Republic of China; 3Department of Nephrology, Changshu Affiliated Hospital of Nanjing University of Chinese Medicine, Changshu, Jiangsu, Peopleâs Republic of ChinaThese authors contributed equally to this workCorrespondence: Meifeng Zhu, Department of Nephrology, Changzhou Hospital Affiliated to Nanjing University of Chinese Medicine, No. 25 Heping North Road, Tianning District, Changzhou, Jiangsu, 213003, Peopleâs Republic of China, Email zhumeifeng@njucm.edu.cn Ying Zhu, Department of Nephrology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, No. 6 Huanghe Road, Suzhou, Jiangsu, Peopleâs Republic of China, Email drzhu0519@gmail.comAbstract: Diabetic Kidney Disease (DKD) is one of the common and serious microvascular complications of diabetes, and the pathogenesis is complex and incompletely understood. Recent studies have shown that lactylation, as a novel form of protein post-translational modification, has been increasingly involved in the progression of DKD through the specific binding of lactate molecules to protein amino acid residues, particularly involving important pathological processes such as inflammatory regulation, cell death-related signaling pathways and fibrotic remodeling. This review summarizes current evidence on abnormal lactate metabolism in DKD and the mechanisms by which lactate-driven lactylation regulates signaling pathways associated with kidney injury. It further evaluates the potential of lactate as a clinical biomarker and discusses intervention strategies targeting lactate metabolism as well as enzymes involved in lactylation and delactylation. These findings provide new insights and future research directions for the prevention and treatment of DKD.Plain Language Summary: Diabetic kidney disease is a major cause of chronic kidney failure in people with diabetes, yet current treatments do not fully prevent disease progression. Understanding the biological mechanisms that drive kidney damage remains essential for developing better therapies. This review examines how changes in cellular metabolism contribute to diabetic kidney disease, with a focus on lactate, a key product of glucose metabolism. Beyond its traditional role in energy production, lactate can modify proteins through a process known as lactylation, which influences gene activity and cellular behavior. Recent studies suggest that abnormal lactate metabolism and protein lactylation may promote inflammation, tissue scarring, and cell dysfunction in the diabetic kidney. We summarize current evidence from experimental and clinical studies linking lactate-related pathways to kidney injury and disease progression. We also discuss the limitations of existing research and highlight important gaps that require further investigation. By clarifying how metabolic signals influence kidney pathology, this review provides insight into potential therapeutic targets and supports future research aimed at improving outcomes for people with diabetic kidney disease.Keywords: diabetic kidney disease, lactate, lactate metabolism, glycolysis, post-translational modification, protein lactylation, renal fibrosis
Sun et al. (Fri,) studied this question.