Renal metabolism of amino acids and ammonia in subjects with normal renal function and in patients with chronic renal insufficiency.

Abstract

A B S T R A C T The net renal metabolism of amino acids and ammonia in the post absorptive state was evaluated in subjects with normal renal functioin and in patients with chronic renal insufficiency by measuring renal uptake and release, and urinary excretion of free amino acids and ammonia. In normial subjects the kidney extracts glutamine, proline, citrulline, and phenylalanine and releases serine, arginine, taurine, threonine, tyrosine, ornithine, lysine, and perhaps alanine. The renal uptake of amino acids from arterial blood occurs by way of plasma only, whereas approximately a half of amino acid release takes place by way of blood cells. Glycine is taken up from arterial plasma, while similar amounts of this amino acid are released by way of blood cells. In the same subjects total renal ammonia production can be largely accounted for by glutamine extracted.In patients with chronic renal insufficiency (a) the renal uptake ofphenylalanine and the release oftaurine and ornithine disappear; (b) the uptake of glutamine and proline, and the release of serine and threonine are reduced by 80-90%; (c) the uptake of citrulline and the release of alanine, arginine, tyrosine, and lysine are reduced by 60-70%; (d) no exchange of glycine is detectable either by way of plasma or by way of blood cells; (e) exchange of any other amino acid via blood cells disappears, and (f) total renal ammonia production is reduced and not more than 35% of such production can be accounted for by glutamine extracted, so that alternative precursors must be used. A 140% excess of nitrogen release found in the same patients suggests an intrarenal protein and peptide breakdown, which eventually provides free amino acids for ammonia production.

High plasma arginine concentrations in critically ill patients suffering from hepatic failure

“…The kidney synthesizes arginine from citrulline and a nitrogen donor, usually aspartic acid (Borsook & Dubnoff, 1941). In patients with chronic renal failure, it has been shown that a net citrulline uptake was balanced by an equal net arginine output, which on the overall was 40% less than in healthy humans (Tizianello et al, 1980). In our study, we show that plasma concentrations of arginine are independently and negatively associated with the presence of renal failure in critically ill patients.…”

Arginine metabolism: nitric oxide and beyond

“…As expected, individuals with chronic renal insufficiency have elevated plasma levels of citrulline [116,120,121]. Surprisingly, however, there is little or no decrease in plasma arginine in these patients.…”

“…Approximately 60 % of net arginine synthesis in adult mammals occurs in the kidney [50,60], where citrulline is extracted from the blood and converted stoichiometrically into arginine by the action of ASS and ASL (Figure 2), which are localized within the proximal convoluted tubules [81,[112][113][114][115]. A tight correlation between renal citrulline uptake and renal arginine output has been elegantly demonstrated for both humans and rats [50,116]. Furthermore, in i o rates of arginine synthesis in adult rats are limited primarily by the amount of citrulline produced by other organs, such as the small intestine, rather than by the renal arginine biosynthetic capacity [50].…”

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

“…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.…”