title: Growth hormone, insulin-like growth factors and their binding proteins in adult hemodialysis patients treated with recombinant human growth hormone.
abstract: BACKGROUND
  Growth deficiency and malnutrition in uremic children are often caused by malfunction of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis and can be corrected by treatment with GH. The purpose of this study was to evaluate the levels of GH, IGF-I and II and their binding proteins compared to changes in body composition in adult, enfeebled, uremic patients in chronic hemodialysis (HD), treated for 6 months with recombinant human growth hormone (rhGH).
  
  
  METHODS
  31 patients were included in a controlled, randomized, double-blinded study using either 4 IU/m2/day of rhGH or placebo injected subcutaneously every evening for 6 months.
  
  
  RESULTS
  Fasting levels of GH were normal at start and increased significantly from 2.2 to 13.5 microg/l (p = 0.01) within the first 4 months of rhGH treatment. Before treatment IGF-I was at the upper limit of normal range (130 to 220 microg/l) in both groups, and it increased significantly from 213 to 348 microg/l (p = 0.01) during rhGH treatment. IGF-II was above the normal range in both groups, and remained unchanged throughout. IGFBP-1 decreased in the rhGH-treated group from 53.1 to 24.7 microg/l (p = 0.004), while IGFBP-3 increased from 5620 to 7100 microg/l (p = 0.004). The molar ratio of IGF-I/IGFBP-3 increased significantly from 14 to 25% (p = 0.01), while the ratio decreased in the placebo group (p = 0.01). During the treatment with rhGH the patients increased their lean body mass (= muscle mass) by a median of 3.18 kg (range 0.82 to 5.12 kg) (p = 0.0001) while their fat mass decreased by a median of 3.33 kg (range 0.18 to 5.82 kg) (p = 0.004). Total body mass (= weight) remained stable. No significant changes were observed in the placebo group.
  
  
  CONCLUSIONS
  The baseline GH and IGF-I concentrations were normal in malnourished HD patients. When treated with rhGH in a dosage as used in growth-retarded uremic children, IGF-I increased to the levels seen in acromegalic persons. IGF-I increased more than IGFBP-3 whereby its biological activity obviously improved. This was reflected in an increased muscle mass and a decreased fat mass. The rhGH treatment was well tolerated.
authors.affiliation: Department of Nephrology, Odense University Hospital, Denmark.
authors.forename: P B
authors.initials: PB
authors.lastname: Jensen
authors.forename: T B
authors.initials: TB
authors.lastname: Hansen
authors.forename: J
authors.initials: J
authors.lastname: Frystyk
authors.forename: S D
authors.initials: SD
authors.lastname: Ladefoged
authors.forename: F B
authors.initials: FB
authors.lastname: Pedersen
authors.forename: J S
authors.initials: JS
authors.lastname: Christiansen
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001823:Body Composition; D015992:Body Mass Index; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000033:anatomy & histology; D009748:Nutrition Disorders / Q000628:therapy; D010919:Placebos; D011994:Recombinant Proteins; D006435:Renal Dialysis; D014511:Uremia / Q000628:therapy
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D010919:Placebos; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II