title: Renal cortical pyruvate as a potentially critical mediator of acute kidney injury.
abstract: Pyruvate is a key intermediary in both aerobic and anaerobic energy metabolisms. In addition, a burgeoning body of experimental literature indicates that it can also dramatically impact oxidant, proinflammatory, and cytoprotective pathways. In sum, these actions can confer protection against diverse forms of tissue damage. However, the fate of pyruvate during the evolution of acute kidney injury (AKI) has remained ill defined. Recent experimental studies have indicated that following either ischemic or nephrotoxic renal injury, marked and sustained pyruvate depletion results. While multiple potential mechanisms for this pyruvate loss may be involved, experimental data suggest that a loss of lactate (a dominant pyruvate precursor) and enhanced gluconeogenesis (i.e. pyruvate utilization) are involved. The importance of pyruvate depletion for AKI pathogenesis is underscored by observations that pyruvate therapy can attenuate diverse forms of experimental AKI. This protection may stem from reductions in tissue inflammation, improved anti-inflammatory defenses, and an enhanced cellular energy metabolism. The pieces of information that give rise to these conclusions are discussed in this brief report.
authors.affiliation: Department of Medicine, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, Wash., USA.
authors.forename: Ali C M
authors.initials: AC
authors.lastname: Johnson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Zager
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D015687:Cell Hypoxia; D003653:Decarboxylation; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005943:Gluconeogenesis; D006019:Glycolysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply; D007672:Kidney Cortex / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011773:Pyruvates / Q000378:metabolism*; D012206:Rhabdomyolysis / Q000150:complications
chemical_list: D000975:Antioxidants; D007773:Lactates; D011773:Pyruvates; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide