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.

Muscle protein turnover and amino acid (AA) exchange across the forearm were studied in nine postabsorptive patients with chronic renal failure (CRF) under unrestricted calorie-protein diets and eight controls by using the arterio-venous difference technique associated with the 3H-phenylalanine kinetics. In patients with CRF: (1) the rate of appearance (Ra) of phenylalanine (Phe) from the forearm, reflecting proteolysis, was 27% increased in comparison with controls (P < 0.01). Also the rate of disposal (Rd) of Phe, reflecting protein synthesis, was increased in patients (P < 0.01). As a consequence of these counterbalanced alterations, net balance of Phe across the forearm, that is, net proteolysis, was not changed. (2) The release of total AA from the forearm was not different from controls. Valine and ketoisocaproate release was reduced (P < 0.05). Serine uptake was not detectable. (3) Net proteolysis and the Rd/Ra ratio were inversely and directly, respectively, related to arterial [HCO3-] (P < 0.02 and P < 0.03, respectively). (4) Moreover, net proteolysis and Phe Rd/Ra ratio were directly and inversely, respectively, correlated with plasma cortisol (P < 0.01 and < 0.005, respectively). Plasma cortisol was in the normal range and inversely related to arterial [HCO3-] (P < 0.02). (5) While in controls phenylalanine appearance from the forearm was inversely related to insulin levels, no correlation was found in patients. In conclusion, in patient with CRF, forearm Phe kinetics indicate the existence of an increased muscle protein turnover. Changes in protein synthesis and degradation are well balanced and net proteolysis is not augmented.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the effect of recombinant human growth hormone (rhGH) on muscle protein metabolism in uremic patients with malnutrition, forearm [ 3 H]phenylalanine kinetics were evaluated in six chronically wasted (body weight 79% of ideal weight) hemodialysis (HD) patients in a self-controlled, crossover study. Forearm protein dynamics were evaluated before, after a 6-wk course of rhGH (5 mg thrice weekly) and after a 6-wk washout period. After rhGH: ( a ) forearm phenylalanine net balance-the difference between phenylalanine incorporation into and phenylalanine release from muscle proteins-decreased by 46% ( Ϫ 8 Ϯ 2 vs. Ϫ 15 Ϯ 2 nmol/min·100 ml at the baseline and Ϫ 11 Ϯ 2 after washout,

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.

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Two severe hemolytic crises, in a month’s period, were induced by primaquine in a glucose-6-phosphate dehydrogenase deficient Sardinian male. Young red blood cells tagged with Fe59 10 to 16 days earlier were destroyed in the second hemolytic episode. The implications of these experiments on the nature of drug-induced hemolysis in Caucasians are briefly discussed.

1. Arterial concentration and arterial-venous differences of glutamine across the kidney, forearm, hepato-splanchnic bed and brain were measured in patients with chronic renal insufficiency and in patients with normally functioning kidneys before and during chronic ammonium chloride acidosis. 2. In chronic renal insufficiency and in chronic metabolic acidosis there is a rise in glutamine release from the muscles and a suppression of glutamine uptake by the hepato-splanchnic bed and the brain. 3. In chronic renal insufficiency arterial glutamine concentrations is significantly increased in comparison with subjects with normal renal function and either normal acid-base balance or chronic metabolic acidosis. 4. In patients with chronic renal insufficiency the kidney extracts negligible amounts of glutamine, which cannot account for the renal ammonia production measured in the same patients.

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