Influence of growth hormone on whole body and regional soft tissue composition in adult patients on hemodialysis. A double-blind, randomized, placebo-controlled study
Tb. Hansen et al., Influence of growth hormone on whole body and regional soft tissue composition in adult patients on hemodialysis. A double-blind, randomized, placebo-controlled study, CLIN NEPHR, 53(2), 2000, pp. 99-107
Background: Many adult patients in chronic hemodialysis exhibit malnourishm
ent 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 pers
ons, 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 m
ass and fat mass (FM). Design: The study was double-blinded, randomized, an
d placebo-controlled. Twenty enfeebled patients in chronic hemodialysis wer
e treated by subcutaneous injections of biosynthetic human GH (4 IU/m(2) pe
r day) or placebo, given every evening for 6 months. Soft tissues as LBM an
d FM, were measured by DXA scan, and height, and weight were recorded befor
e, and after 6 months treatment. Serum concentration of insulin-like growth
factor (IGF-1) and type III collagen N-terminal propeptide (PIIINP) were a
nalyzed 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) corr
esponding 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, t
otal body weight remained unchanged. Serum IGF-1 increased from 199 +/- 14.
8 mu g/l to 527 +/- 111 mu Lg/l (p < 0.0001) at month 6, and the serum PIII
NP from 7.8 +/- 1.3/mu g/l to 14.3 +/- 2.1 mu g/l (p < 0.001) in the GH-tre
ated group. In the placebo group (n = 11) there were no significant changes
in FM, LBM or PIIINP while serum IGF-1 decreased from 285 +/- 36 mu g/l to
219 +/- 35 mu g/l (p < 0.01) after 6 months treatment. Conclusions: Six mo
nths of GH therapy to patients with chronic renal failure resulted in marke
d changes of the soft tissue with an increase in LBM, and reduction of FM p
articularly at the trunk. The data imply that GH-induced changes in body co
mposition are maintained with long-term therapy. Very few side-effects of G
H 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-1 concentrations during treatment equali
zed those seen in acromegalia. This indicates the existence of a reduced bi
ological effect of GH and IGF-1 in uremic persons.