Experimental Fanconi's syndrome resulting from 4-pentenoate infusion in the dog

Abstract

Studies were performed in anesthetized dogs to evaluate the effects of 4-pentenoate on urinary electrolyte excretion and renal metabolism. The intravenous administration of 4-pentenoate (1 mumol.kg-1.min-1 during 180 min) markedly increased the urinary excretion of bicarbonate, phosphate, potassium, amino acids, glucose, and various organic anions, whereas that of sodium and chloride also rose but less strikingly. These results suggest that 4-pentenoate markedly inhibits the proximal reabsorption of various solutes and therefore reproduces an experimental Fanconi's syndrome. Despite the rise in renal cortical concentration of alpha-ketoglutarate, glutamine utilization and total ammonia production expressed per 100 ml glomerular filtration rate increased following 4-pentenoate infusion, the ammonia being diverted into the renal vein. This increment in glutamine utilization was equal to the combined rise in the renal production of glutamate and alpha-ketoglutarate. By contrast, renal lactate utilization was drastically reduced. A causal relationship between the decreased renal cortical ATP concentration and the inhibited reabsorption of various solutes is suggested but cannot be established unequivocally.