Skeletal muscle protein synthesis and degradation in patients with chronic renal failure

Abstract

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)

Effects of recombinant human growth hormone on muscle protein turnover in malnourished hemodialysis patients.

“…The changes induced by the administration of rhGH were reversed by rhGH discontinuation. Baseline rates of appearance and disposal of phenylalanine measured in this group of malnourished patients are about 30% lower than those measured in well nourished CRF patients under unrestricted diets (4,29) and are also in the lower range of the values recorded in normal subjects in the literature (23,30) and in our laboratory (4). This observation suggests that low rates of protein synthesis occur in the muscle of malnourished HD patients and is in accordance with studies showing a decrease in RNA/DNA ratio in muscle in such patients (31).…”

“…Phenylalanine Ra was calculated as follows (23,4): Ra ϭ blood flow ϫ [V] ϫ (1 Ϫ SAv/SAa), where [V] is the venous blood level of phenylalanine, and SAa and SAv indicate the specific activity (dpm/ nmol) of phenylalanine in the artery and vein, respectively. The term (1 Ϫ SAv/SAa) expresses the dilution of tracer specific activity across the forearm caused unlabeled phenylalanine released by muscle.…”

“…The present study was designed to determine the effects of rhGH on protein metabolism, amino acid exchange, and potassium balance in the muscle of nonacidotic HD patients with protein calorie malnutrition by using the forearm perfusion technique associated with [ 3 H]phenylalanine infusion (23,4). Changes in muscle protein dynamics were evaluated in relation to variations in circulating IGF-I and IGFBPs.…”

“…An inadequate protein-calorie intake, the increase in muscle protein degradation caused by metabolic acidosis (2)(3)(4), and the loss of amino acids during the dialytic procedure (5) are major causes of malnutrition. However, recent evidence indicates that chronic renal failure is also characterized by a resistance to anabolic hormones, such as growth hormone (GH) and insulin-like growth factor-I (IGF-I).…”

Insulin Is Protein-Anabolic in Chronic Renal Failure Patients

“…To account for the drift in breath 13 CO 2 due to the presence of natural 13 C abundance in the dextrose and Travasol solutions, separate studies were performed in four subjects, two controls and two B-HD patients, in whom breath 13 CO 2 was measured during identical insulin and Travasol infusion, but without the stable isotopes. The magnitude of the drift in 13 CO 2 between the controls and the CRF patients was not different.…”