Amino acid profiles and muscle protein composition in rats with a reduced renal mass in the fed state.

In severe chronic renal failure (CRF) with associated metabolic acidosis, abnormalities in protein metabolism and amino acid (AA) profiles in the fed state are well described. To evaluate the effect of early uraemia and the influence of acid-base status on protein metabolism and AA profiles, three groups of pair-fed rats were studied: group I - rats with 1+ 1/2 nephrectomy; group II - rats with 1+ 1/2 nephrectomy receiving NaHCO3 supplementation, and group III - sham-operated rats with NaHCO3 supplementation. After 4 weeks, serum creatinine values were similar in groups I and II (111 +/- 5 and 119 +/- 4 mumol/l) and higher than in group III (51 +/- 5 mumol/l, p < 0.0001); HCO-3 was reduced only in group I (22.4 +/- 0.8 mmol/l) compared to group II (28.3 +/- 0.6 mmol/l, p < 0.001) and group III (28.2 +/- 1.3 mmol/l, p < 0.001). In the uraemic animals (groups I and II) arterial AA profiles showed increased levels of phenylalanine, glycine, glutamate, proline and alanine. The marked increase of threonine in group I was corrected by NaHCO3 supplementation in group II. The total nonessential AA were higher both in group I (1,832 +/- 53 mumol/l, p < 0.05) and group II (1,788 +/- 103 mumol/l, p < 0.05) than in group III (1,542 +/- 54 mumol/l). These results are similar to those described in the fed state of uraemic patients. Intracellular AA changes were detected, especially in group II namely increased glycine and a decrease in threonine and serine levels. No signs of malnutrition or changes in alkali-soluble protein (ASP) or ASP/DNA ratio in liver and muscle were observed. These results show that AA abnormalities in the fed state occur early in the course of CRF, and that the marked increase of threonine is corrected by NaHCO3 supplementation. These data suggest that either an impaired utilization of the ingested proteins might occur before the appearance of major alterations in endogenous protein metabolism or acid-base status might alter AA metabolic rate per se

Effects of acid loading on serum amino acid profiles and muscle composition in normal fed rats.

1. Impaired body growth, loss of lean body mass and negative nitrogen balance are common findings in chronic renal failure. Enhanced endogenous protein catabolism in skeletal muscle induced by co-existent metabolic acidosis seems to be an important aetiological factor. 2. In uraemic patients abnormalities in blood amino acid profiles are present after a protein meal, suggesting impaired metabolism of ingested proteins. 3. This study demonstrates that acidosis induces changes in arterial amino acid profiles in fed non-uraemic rats. These included increased levels of threonine, histidine, proline, serine and glycine, and decreased levels of tryptophan. These changes are similar to those found in uraemic patients after a protein meal, suggesting a pathogenic role of acidosis in the impairment of exogenous protein metabolism. 4. Intracellular amino acid levels in the muscle tissue partly reflect the changes in the extracellular level. 5. Acidotic animals had a decreased body weight gain and a reduced alkali-soluble protein/DNA ratio in muscle cells compared with controls. 6. In conclusion, the results show that acidosis per se modifies the circulating amino acid profile in fed rats, resulting in a pattern similar to the post-prandial amino acid changes described in uraemic patients. These abnormalities occur together with impaired growth of skeletal muscle cells