Uremic encephalopathy: role of brain energy metabolism.
Uremia is associated with decreased brain oxygen consumption in humans and with decreased brain energy consumption in rodent models of acute renal failure. We measured the levels of high-energy phosphates and glycolytic intermediates in the brain of dogs with acute or chronic renal failure. We used methods of rapid brain tissue fixation that trap these labile metabolites at their in vivo levels. Creatine phosphate, ATP, and glucose were normal in the brain of animals with renal failure, indicating a normal brain energy reserve. The brain energy charge, which is the fraction of the total adenine nucleotide pool that contains high-energy phosphates, (ATP + 1/2ADP)/(ATP + ADP + AMP), was also normal despite an 8% decrease in the total adenine nucleotide pool. Mild hypoxia failed to alter the level of any of these metabolites. The brain redox state, (NAD+)/(NADH), was normal to high in acute renal failure, suggesting that oxygen supply was not limiting oxygen consumption. In the face of normal brain energy reserves, energy charge, and redox state, the decreased energy consumption of uremic brain probably results from decreased demand rather than limited supply.
D058186:Acute Kidney Injury / Q000150:complications / Q000378:metabolism; D000758:Anesthesia; D000772:Anesthesia, Local; D000818:Animals; D001463:Barbiturates; D001921:Brain / Q000378:metabolism*; D001927:Brain Diseases / Q000209:etiology / Q000378:metabolism*; D004285:Dogs; D004734:Energy Metabolism; D000860:Hypoxia / Q000378:metabolism; D014511:Uremia / Q000150:complications*
D001463:Barbiturates