Renal tubular biochemistry during acute and chronic metabolic alkalosis in the dog.

Acute metabolic alkalosis was induced in dogs by the infusion of sodium bicarbonate, 0.3 M. Chronic alkalosis was induced by chloride restriction and the administration of sodium bicarbonate and furosemide. In a third group of dogs, potassium was added to the regimen to prevent frank potassium depletion. Plasma bicarbonate ranged from 29.0 to 32.9 mM. In all three dog groups, renal ammoniagenesis fell by over 30%, which was consistent with a decrease in the renal uptake of glutamine. Glutamate was released in the renal vein and alanine production was decreased. Total production of ammonia was lowest in the animals given a potassium supplement where muscle potassium decreased much less than in the other chronic animals. Urinary ammonia excretion was very low in all three animal groups; this was related to an alkaline urine. However, this relationship was not entirely consistent and the low excretion of ammonia could also be related to decreased ammonia production by the renal tubular cell. In the renal cortical tissue (freeze-clamped), the concentration of glutamate did not change and that of alpha-ketoglutarate rose only in the animals supplemented with potassium. Malate rose in all groups. In all animals, renal tissue concentration of lactate and citrate rose while citrate excretion increased. We feel that glycolysis could play an important role in renal metabolism during acute and chronic metabolic alkalosis. We have proposed a unified theory to explain the metabolic changes that occur in lactate and citrate metabolism during metabolic alkalosis with a depressing effect on ammoniagenesis. Although citrate could be generated in the mitochondria from pyruvate, its oxidation is probably inhibited with exit and accumulation in the cytosol.