SKELETAL-MUSCLE PROTEIN-SYNTHESIS AND DEGRADATION IN PATIENTS WITH CHRONIC-RENAL-FAILURE

Skeletal muscle protein synthesis and degradation in patients with chr onic renal failure. Muscle protein turnover and amino acid (AA) exchan ge across the forearm were studied in nine postabsorptive patients wit h chronic renal failure (CRF) under unrestricted calorie-protein diets and eight controls by using the arterio-venous difference technique a ssociated with the H-3-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 control s (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 the se counterbalanced alterations, net balance of Phe across the forearm, that is, net proteolysis, was not changed. (2) The release of total A A from the forearm was not different from controls. Valine and ketoiso caproate release was reduced (P<0.05). Serine uptake was not detectabl e. (3) Net proteolysis and the Rd/Ra ratio were inversely and directly , respectively, related to arterial HCO3- (P<0.02 and P<0.03, respec tively). (4) Moreover, net proteolysis and Phe Rd/Ra ratio were direct ly and inversely, respectively, correlated with plasma cortisol (P<0.0 1 and <0.005, respectively). Plasma cortisol was in the normal range a nd inversely related to arterial HCO3- (P<0.02). (5) While in contro ls phenylalanine appearance from the forearm was inversely related to insulin levels, no correlation was found in patients. In conclusion, i n patients with CRF, forearm Phe kinetics indicate the existence of an increased muscle protein turnover. Changes in protein synthesis and d egradation are well balanced and net proteolysis is not augmented. How ever, net proteolysis increases in proportion to the degree of metabol ic acidosis because protein synthesis rises less than protein breakdow n. Variations in net proteolysis are best accounted for by changes in plasma cortisol levels, suggesting that cortisol plays an important ro le in variations in muscle net proteolysis in patients with CRF and me tabolic acidosis. A resistance of muscle proteolysis to basal insulin levels likely takes place.