Advancements in early biomarkers of acute kidney injury: from traditional indicators to a paradigm shift in lactate metabolism

Acute kidney injury (AKI) is a severe clinical condition with a high incidence and mortality among hospitalized patients. At present, AKI diagnosis still relies primarily on serum creatinine (SCr) and urine output (UO), which lack sensitivity for early injury and provide limited support for timely intervention. Increasing evidence from metabolomics studies indicates that AKI is characterized by early renal metabolic reprogramming, particularly disturbances in the balance between glycolysis and gluconeogenesis accompanied by abnormal lactate accumulation. This review summarizes recent progress in early biomarkers of AKI, with a specific focus on the auxiliary diagnostic value of lactate metabolism in the early detection and clinical interpretation of AKI. Altered lactate metabolism provides important insights into early renal metabolic stress during AKI. Lactate functions not only as an indicator of mitochondrial dysfunction but also contributes to kidney injury through lactylation, an epigenetic modification derived from lactate. In clinical settings, dynamic changes in lactate levels may signal early metabolic disturbances before overt changes in SCr or UO. Persistent lactate elevation despite haemodynamic stabilisation may reflect early renal metabolic dysregulation, such as localized metabolic reprogramming or reduced clearance. In contrast, lactate increases associated with marked hepatic dysfunction or β₂-agonist use are more often non-renal in origin. These findings underscore the importance of contextual interpretation of lactate across different clinical scenarios. Lactate metabolism provides a metabolic window into early AKI-related renal stress and injury mechanisms. Treating lactate as a complementary marker within a multiparametric diagnostic framework, rather than relying on a single threshold, may enable earlier recognition of metabolic abnormalities and support more timely and individualized intervention strategies.