Renal ammoniagenesis following glutamine loading in intact dogs during acute metabolic acid–base perturbations

Abstract

Adaptation of renal ammoniagenesis during acute metabolic acidosis in intact dogs may be nonexistent or, at least, markedly less than in chronic acidosis. This contrasts to adaptation in acute respiratory acidosis, where levels similar to those attained in chronic acidosis occur within hours. Accordingly, the inability to discern marked changes in acute metabolic acidosis compared with acute respiratory acidosis has been attributed to decreased glomerular filtration rate and renal blood flow seen frequently in the former. In our studies, we found early changes in ammoniagenesis and glutamine metabolism during acute metabolic acidosis, but not of the magnitude seen in chronic acidosis, even considering the changes in renal blood flow (RBF) and glomerular filtration rate (GFR). Exogenous glutamine loading allowed us to discover that the qualitative changes in glutamine metabolism during acute metabolic acidosis differed from control but fell short of those seen in chronic metabolic a acidosis. We also examined glutamine metabolism when renal ammoniagenic adaptation was acutely inhibited in chronically acidotic dogs. Infusing NaHCO3 into chronically acidotic dogs decreased renal ammonia production significantly (247 mumol min-1 100 ml-1 GFR vs 148 mumol min-1 100 ml-1 GFR: P less than 0.001) and glutamine extraction (111.8 mumol min-1 100 ml-1 GFR vs 90.9 mumol min-1 100 ml-1 GFR: P less than 0.02). The qualitative changes in renal glutamine metabolism in both studies suggest that alterations in deamination of glutamate formed from glutamine are responsible, at least in part, for adaptation to acute acid-base perturbations. Compared with respiratory acidosis, adaptation to metabolic acidosis is progressive and prolonged.

The effect of acidosis on the labelling of urinary ammonia during infusion of [amide-15N]glutamine in human subjects

“…If the precursors remain essentially unchanged, a 3-fold increase in NH, output will represent a 3-fold increase in the rate of GLN extraction by the kidney. Thus, in the dog, Areas et al (1987) found a linear relationship between renal GLN extraction and urinary NH, production. Similar results have been recorded by others; in man by Owen & Robinson (1963) and Tizianello et al (1978), in sheep by Heitmann & Bergman (1978), in the dog by Lotspeich (1967) and Cersosimo et al (1986) and in the rat by Goldstein et al (1980) and Welbourne (1988).…”

“…Further studies on acidosis with [15N]glycine as tracer will be reported later. There is a large amount of information in the literature on glutamine metabolism and its relationship to renal NH, production in man (Owen & Robinson, 1963;Pitts & Pilkington, 1966;Tizianello et al 1978Tizianello et al , 1982, sheep (Heitmann & Bergman, 1978), dog (Pitts et al 1965;Cersosimo et al 1986;Areas et al 1987) and the rat (Squires et al 1976;Schrock & Goldstein, 1981;Squires & Brosnan, 1983;Welbourne, 1986). However, we know of only three studies on man and none on experimental animals in which glutamine labelled with 15N was used (Darmaun et al 1986(Darmaun et al , 1988Golden et al 1982), and in none of these was the effect of acidosis examined.…”