Transition of acute kidney injury to chronic kidney disease: role of metabolic reprogramming

Acute kidney injury (AKI) is a global public health concern associated with high morbidity and mortality. Although advances in medical management have improved the in-hospital mortality of severe AKI patients, the renal prognosis for AKI patients in the later period is not encouraging. Recent epidemiological investigations have indicated that AKI significantly increases the risk for the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the future, further contributing to the economic burden on health care systems. The transition of AKI to CKD is complex and often involves multiple mechanisms. Recent studies have suggested that renal tubular epithelial cells (TECs) are more prone to metabolic reprogramming during AKI, in which the metabolic process in the TECs shifts from fatty acid β-oxidation (FAO) to glycolysis due to hypoxia, mitochondrial dysfunction, and disordered nutrient-sensing pathways. This change is a double-edged role. On the one hand, enhanced glycolysis acts as a compensation pathway for ATP production; on the other hand, long-term shut down of FAO and enhanced glycolysis lead to inflammation, lipid accumulation, and fibrosis, contributing to the transition of AKI to CKD. This review discusses developments and therapies focused on the metabolic reprogramming of TECs during AKI, and the emerging questions in this evolving field. Energy metabolic reprogramming during AKI occurs in TECs. In the short term, enhanced glycolysis functions in energy supply and plays an antioxidative stress role, thus alleviating TEC damage. However, long-term energy metabolic reprogramming also promotes the development of AKI and interferes with renal outcomes by enhancing inflammatory responses, lipid accumulation, and fibrosis. [Display omitted] •TECs are highly dependent on FAO to provide energy and rarely perform glycolysis.•The metabolic process in TECs shifts from FAO toward glycolysis during AKI.•Metabolic reprogramming may lead to inflammation, lipid accumulation, and fibrosis, then contributing to the transition of AKI to CKD.