It Takes Two to Tango: The Role of Dysregulated Metabolism and Inflammation in Kidney Disease Development

Abstract

Acute kidney injury is a major contributor of chronic kidney disease development. The pathogenesis of acute kidney injury and chronic kidney disease shows significant similarities. Both conditions are associated with a defect in cellular metabolism, such as fatty acid oxidation and mitochondrial oxidative phosphorylation in kidney tubule cells and a marked increase in infiltrating immune cells. Here, we discuss how inflammatory cytokines and macrophages contribute to epithelial injury and metabolic defects. In addition, we discuss the role of mitochondrial damage and cytosolic leakage of the mitochondrial DNA activating the innate immune pathway such as cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon genes. The interplay between inflammation and metabolism appears to be critical for kidney disease development.

Keywords: cGAS-STING; inflammation; innate immune system; kidney injury; metabolic dysregulation.