Growth hormone, insulin-like growth factors and their binding proteins in adult hemodialysis patients treated with recombinant human growth hormone.
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.
Jensen
P B
PB
Department of Nephrology, Odense University Hospital, Denmark.
Hansen
T B
TB
Frystyk
J
J
Ladefoged
S D
SD
Pedersen
F B
FB
Christiansen
J S
JS
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
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