Plasma glutamine and renal ammoniagenesis in dogs with chronic metabolic acidosis.

Abstract

The purpose of this investigation was to determine whether the rate of glutamine metabolism in the kidneys of normal dogs and dogs with chronic metabolic acidosis was influenced by the plasma glutamine concentration. Because glutamine is a major renal energy fuel, results were examined at a constant rate of energy or ATP turnover [i.e., per 100 ml glomerular filtration rate (GFR)]. Glutamine extraction per 100 ml GFR was directly proportional to the filtered load of glutamine in normal and acidotic dogs. The slope depicting this relationship was parallel to the filtered load of glutamine; however, in normal dogs it was lower and in acidotic dogs it exceeded the filtered load by approximately 22 mumol/100 ml GFR. With respect to the fate of the nitrogens of the glutamine extracted, alanine and ammonium were produced in normal dogs at a rate nearly equivalent to that of glutamine extracted, whereas ammonium production was almost twofold greater than the rate of glutamine extraction during acidosis. There was a relatively small but constant alanine release over the entire range of plasma glutamine concentrations in these dogs. Furthermore, infusion of glutamine to raise the plasma glutamine concentration twofold during acidosis resulted in an increased rate of glutamine extraction and ammonium production equal to that predicted from the increase in filtered load of glutamine. Therefore, variations of circulating glutamine concentration within the physiological range seem to have an important influence on the steady-state rate of renal glutamine metabolism in normal dogs and in dogs with chronic metabolic acidosis.