Influence of growth hormone on whole body and regional soft tissue composition in adult patients on hemodialysis. A double-blind, randomized, placebo-controlled study.
BACKGROUND
Many adult patients in chronic hemodialysis exhibit malnourishment and muscle wasting, which in some may be due partly to blockage of the biological action of growth hormone and the somatomedines. Growth hormone (GH) promotes protein synthesis, and long-term treatment with growth hormone has induced an augmentation in lean body-mass (LBM) in normal elderly persons, in persons with GH deficiency as well as growth improvement in uremic children. The purpose of this study was to evaluate the effect of long-term GH treatment on soft tissues in hemodialyzed patients by dual-energy X-ray absorptiometry (DXA) with special regard to the improvement in lean body mass and fat mass (FM).


METHODS
The study was double-blinded, randomized, and placebo-controlled. Twenty enfeebled patients in chronic hemodialysis were treated by subcutaneous injections of biosynthetic human GH (4 IU/m2 per day) or placebo, given every evening for 6 months. Soft tissues as LBM and FM, were measured by DXA scan, and height, and weight were recorded before, and after 6 months treatment. Serum concentration of insulin-like growth factor (IGF-I) and type III collagen N-terminal propeptide (PIIINP) were analyzed at baseline and after 2, 4 and 6 months.


RESULTS
Six months of GH therapy induced a total FM reduction of 3.05 +/- 0.75 kg (mean +/- SEM) (p < 0.001) (n = 9) corresponding to 25% of the total fat mass. The reduction in fat was most marked at the trunk, i.e. 1.39 +/- 0.41 kg (p < 0.001) corresponding to 40% of the total FM reduction. Total LBM increased by 3.14 +/-0.41 kg (p < 0.001) in the GH group. Regional changes for arm, truncus and leg in GH group amounted to 0.22 +/- 0.06 kg (p < 0.001), 1.64 +/- 0.37 kg (p < 0.001) and 0.51 +/- 0.06 kg (p < 0.001), respectively. In contrast, total body weight remained unchanged. Serum IGF-I increased from 199 +/- 14.8 microg/l to 527 +/- 111 microg/l (p < 0.0001) at month 6, and the serum PIIINP from 7.8 +/- 1.3/microg/l to 14.3 +/- 2.1 microg/l (p < 0.001) in the GH-treated group. In the placebo group (n = 11) there were no significant changes in FM, LBM or PIIINP while serum IGF-I decreased from 285 +/- 36 microg/l to 219 +/- 35 microg/l (p < 0.01) after 6 months treatment.


CONCLUSIONS
Six months of GH therapy to patients with chronic renal failure resulted in marked changes of the soft tissue with an increase in LBM, and reduction of FM particularly at the trunk. The data imply that GH-induced changes in body composition are maintained with long-term therapy. Very few side-effects of GH treatment were observed, and no serious ones were encountered, though the dosage were 2 to 3 times higher than the one given to GH-insufficient, non-uremic persons, and the serum IGF-I concentrations during treatment equalized those seen in acromegalia. This indicates the existence of a reduced biological effect of GH and IGF-I in uremic persons.
Hansen
T B
TB
Department of Endocrinology, Odense University Hospital, Denmark.
Gram
J
J
Jensen
P B
PB
Kristiansen
J H
JH
Ekelund
B
B
Christiansen
J S
JS
Pedersen
F B
FB
D015502:Absorptiometry, Photon / Q000379:methods / Q000706:statistics & numerical data; D000293:Adolescent; D000328:Adult; D000368:Aged; D001823:Body Composition / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010919:Placebos; D006435:Renal Dialysis; D013997:Time Factors
D010919:Placebos; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I