EFFECTS OF RECOMBINANT HUMAN GROWTH-HORMONE ON MUSCLE PROTEIN-TURNOVER IN MALNOURISHED HEMODIALYSIS-PATIENTS

To assess the effect of recombinant human growth hormone (rhGH) on mus cle protein metabolism in uremic patients with malnutrition, forearm [ H-3]phenylalanine kinetics were evaluated in six chronically wasted (b ody weight 79% of ideal weight) hemodialysis (HD) patients in a self-c ontrolled, crossover study. Forearm protein dynamics were evaluated be fore, after a 6-wk course of rhGH (5 mg thrice weekly) and after a 6-w k washout period. After rhGH: (a) forearm phenylalanine net balance-th e difference between phenylalanine incorporation into and phenylalanin e release from muscle proteins-decreased by 46% (-8 +/- 2 vs. -15 +/- 2 nmol/min 100 mi at the baseline and -11 +/- 2 after washout, P < 0.0 2); (b) phenylalanine rate of disposal, an index of protein synthesis, increased by 25% (25 +/- 5 vs. 20 +/- 5 at the baseline and 20 +/- 4 after washout, P < 0.03); (c) phenylalanine rate of appearance, an ind ex of protein degradation, was unchanged (33 +/- 5 vs. 35 +/- 5 at the baseline and 31 +/- 4 after washout); (d) forearm potassium release d eclined (0.24 +/- 0.13 vs. 0.60 +/- 0.15 mu eq/min at the baseline, an d 0.42 +/- 0.20 mu eq/min after washout P < 0.03); (e) changes in the insulin-like growth factor binding protein (IGFBP)-1 levels and insuli n-like growth factor-I (IGF-I)/IGFBP-3 ratios accounted for 15.1% and 47.1% of the percent variations in forearm net phenylalanine balance, respectively; Together, these two factors accounted for 62.2% of varia tions in forearm net phenylalanine balance during and after rhGH admin istration. These data indicate: (a) that rhGH administration in malnou rished hemodialysis patients is followed by an increase in muscle prot ein synthesis and by a decrease in the negative muscle protein balance observed in the postabsorptive state; and (b) that the reduction in n et protein catabolism obtained with rhGH can be accounted for by the a ssociated changes in circulating free, but not total, IGF-I levels.