Renal ammoniagenesis in an early stage of metabolic acidosis in man.

Abstract

A B S T R A C T Total renal ammonia production and ammonia precursor utilization were evaluated in patients under normal acid-base balance and in patients with 24-h NH4C1 acidosis by measuring (a) ammonia excreted with urine and that added to renal venous blood, and (b) amino acid exchange across the kidney. In 24-h acidosis not only urinary ammonia excretion is increased, but also total ammonia production is augmented (P < 0.005) in comparison with controls. By evaluating the individual role of acid-base parameters, urine pH and urine flow in influencing renal ammonia production, it was shown that the degree of acidosis and urine flow are likely major factors stimulating ammoniagenesis. Both urine pH and urine flow are determinant in the preferential shift of ammonia into urine. In 1-d acidosis, renal extraction of glutamine was not increased and the total ammonia produced/ glutamine N extracted ratio was higher than in controls (P < 0.005) and was inversely correlated with the log of arterial bicarbonate concentration (P < 0.001). In the same condition, renal glycine and ornithine uptake took place; the more severe the acidosis, the greater was the renal extraction of these amino acids (P < 0.001). These data indicate that at the early stages of metabolic acidosis, in spite of a brisk increase in ammonia production, the mechanisms responsible for the increased glutamine use, which are operative in chronic acidosis, are not activated and other ammonia precursors, besides glutamine, are probably used for ammonia production.

Renal substrate exchange and gluconeogenesis in normal postabsorptive humans

“…Our net renal balance data for alanine, glycerol, and glutamine are in general agreement with previous reports (9,12,16,31,49,50). Our data for renal lactate net uptake (ϳ170 mol/min) are essentially identical to those reported by Cersosimo and colleagues (9, 12) (ϳ170 mol/min).…”

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

“…In rats and humans, glutamine is the major precursor of the ammonia produced during acidosis (25,26,32). Data presented here show that glutamine uptake by the kidney in acidotic subjects was 120% higher than what was observed in subjects with normal acid-base balance.…”

“…In normal acid-base conditions the glutamine N extraction by the kidney is greater than the amount of ammonia that is produced, thus indicating that N supplied by glutamine extraction is more than sufficient to account for ammonia production (18,25,26). In the acidotic subjects we studied, the ratio of ammonia production to glutamine nitrogen extracted by the kidney was close to unity.…”

“…It is noteworthy that an uptake of glycine by the human kidney can be observed 24 h after the onset of metabolic acidosis (26), thus showing that pathways for glycine transport and or metabolism are precociously stimulated by acidemia. Although the reduced release of glutamate is consistent with its use as an ammoniagenic source, the decrease in kidney amino acid output (such as tyrosine and serine) is in agreement with the decrease in intrarenal protein breakdown that is observed in acidemic subjects.…”

Nutritional support with glutamine according to recommendations of the European Society for Clinical Nutrition and Metabolism (ESPEN)

“…W wątrobie uczestniczy w syntezie glukozy, mocznika, glutationu, bierze udział w syntezie aminokwasów [5]. W jelicie cienkim i nerkach stanowi źródło energii, w nerkach ponadto uczestniczy w syntezie glukozy i utrzymaniu równowa-gi kwasowo-zasadowej [6,7]. We wszystkich tkankach glutamina bierze udział w syntezie białek i w syntezie puryn i pirymidyn niezbędnych do powstania kwasów nukleinowych.…”