1. Free amino acids were determined in the plasma and in the muscle tissue of 14 patients with chronic uraemia; eight were not on dialysis and six were having regular peritoneal dialysis. The concentration of each amino acid in muscle water was calculated with the chloride method. 2. In both groups of patients there were low intracellular concentrations of threonine, valine, tyrosine and carnosine, and high glycine/valine and phenylalanine/tyrosine ratios. Both groups of patients had increased amounts of 1- and 3-methyl-histidine in plasma and in muscle water. 3. The non-dialysed patients had low intracellular concentrations of lysine, and the dialysed patients had high intracellular concentrations of lysine, isoleucine, leucine and of some of the non-essential amino acids. 4. After peritoneal dialysis for 22 h, the plasma concentration of several amino acids decreased but the intracellular concentrations of most amino acids did not change significantly. 5. Intravenous administration of essential amino acids and histidine during the last 4 h of dialysis increased in muscle the total free amino acids, the ratio of essential to non-essential amino acids and the valine and phenylalanine concentrations. 6. The results demonstrated that the plasma and muscle concentrations of several amino acids are grossly abnormal in chronic uraemia. Non-dialysed and dialysed patients exhibit important differences, especially in the intracellular amino acid patterns. Infusion of essential amino acids may result in enhancement of protein synthesis.
A dietary regimen employing a protein-poor diet (2.7–3 g N/day) supplemented by essential amino acids, given intravenously or orally, changed the nitrogen balance in severe uremic patients from a negative to a positive one. The addition of histidine to the essential amino acids further improved the nitrogen balance. No difference in the nitrogen balance was observed when intravenous (i.v.) and oral administration were compared. 15N studies indicate that protein synthesis takes place preferably in the muscle cells when the amino acids are infused intravenously, whereas oral treatment resulted in preferential synthesis of plasma protein. Insufficient caloric intake, lack of non-essential nitrogen, potassium depletion, corticosteroid administration, infection or cardiac insufficiency have been found to cause a deterioration of the nitrogen balance and an increase of plasma urea or concentration. In preliminary studies, administration of human growth hormone (HGH) to uremic patients maintained on the protein-poor diet was found to further improve the nitrogen balance. In other preliminary experiments, administration of extra tryptophan with the diet amino acids to uremic patients was also found to improve the nitrogen balance.
Patients (N = 8) with chronic renal failure and uremia treated with hospital hemodialysis were in a pilot study investigated before and after a single hemodialysis session. The extracorporeal dialysis circuit was flushed regularly with saline to avoid clotting and the use of heparin. Percutaneous skeletal muscle biopsies were taken before and after the dialysis to determine the content of free amino acids together with the concentration and size distribution of ribosomes before and after dialysis. After dialysis the alanine concentration in muscle decreased by 20% (P less than 0.05), while all other amino acids were unaffected. The total ribosome concentration per mg of DNA decreased by 31% (P less than 0.01) and the relative proportion of polyribosomes by 7% (P less than 0.05) after the dialysis compared to predialytic values. All individual plasma amino acids decreased during the dialysis procedure except for threonine and arginine, which were unaltered, and leucine and isoleucine, which increased. The decline in ribosome and polyribosome content together with the changes in amino acid levels indicate a low capacity for protein synthesis and increased catabolism in muscle of hemodialyzed patients.
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