Lactate and Lactylation in AKI-to-CKD: Epigenetic Regulation and Therapeutic Opportunities

Lactate is not only a byproduct of glycolysis, but is also considered an energy source, gluconeogenic precursor, signalling molecule and protein modifier during the process of cellular metabolism. The discovery of lactylation reveals the multifaceted functions of lactate in cellular metabolism and opens new avenues for lactate-related research. Both lactate and lactylation have been implicated in regulating numerous biological processes, including tumour progression, ischemic-hypoxic injury, neurodevelopment and immune-related inflammation. The kidney plays a crucial role in regulating lactate metabolism, influencing lactate levels while also being regulated by lactate. Previous studies have demonstrated the importance of lactate in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease (CKD). This review explores the role of lactate and lactylation in these diseases, comparing the function and metabolic mechanisms of lactate in normal and diseased kidneys from the perspective of lactylation. The key regulatory roles of lactylation in different organs, multiple systems, various pathological states and underlying mechanisms in AKI-to-CKD progression are summarised. Moreover, potential therapeutic targets and future research directions for lactate and lactylation across multiple kidney diseases are identified.