Metabolism as Disease Tolerance: Implications for Sepsis-Associated Acute Kidney Injury

Sepsis is a significant cause for mortality among critically ill patients. Metabolic derangements that develop in sepsis are often considered to be pathologic, contributing to sepsis morbidity and mortality. However, alterations in metabolism during sepsis are multifaceted and are incompletely understood. Acute anorexia during infection is an evolutionarily conserved response, suggesting a potential protective role of anorexia in the host response to infection. In animal models of bacterial inflammation, fasting metabolic programs associated with acute anorexia such as those regulated by fibroblast growth factor 21 and ketogenesis are associated with improved survival. Other fasting metabolic pathways such as fatty acid oxidation and autophagy are also implicated in preventing acute kidney injury (AKI). Global metabolic changes during sepsis and current clinical interventions can potentially affect disease tolerance mechanisms and modify the risk of AKI.