Short-term administration of a combination of recombinant growth hormone and insulin-like growth factor-I induces anabolism in maintenance hemodialysis.
BACKGROUND
Resistance to GH and IGF-I is a significant complication of severe chronic kidney disease, which contributes to muscle wasting. Pharmacological doses of recombinant human (rh) GH or rhIGF-I have been proposed to treat this catabolic condition.


OBJECTIVE
This study was undertaken to examine the potential additive anabolic effects of rhGH + rhIGF-I compared with rhIGF-I.


METHODS
We studied eight well-nourished hemodialysis patients in a random crossover design and compared the metabolic effects of a 3-d administration of moderate dose of rhIGF-I (40 microg/kg per 12h) with an association of rhIGF-I + rhGH (50 microg/kg/d). Leucine kinetics, plasma amino acids (AAs), serum insulin, and IGF binding proteins (IGFBP)-1 and -3 were measured.


RESULTS
The net protein balance was not affected by rhIGF-I alone, whereas serum insulin and IGFBP-3 decreased (P < 0.05) and IGFBP-1 increased (P < 0.01). With the combination rhGH + rhIGF-I, an increase of IGFBP-3 (P < 0.01) and insulin (P < 0.01) as well as a decrease of IGFBP-1 (P < 0.01) occurred. Plasma essential AAs (P = 0.01) as well as the essential to nonessential AA ratio (P < 0.001) decreased. Whole-body protein net balance increased significantly (P < 0.05) with a 22% decrease in leucine oxidation and a 15% increase in nonoxidative leucine disposal.


CONCLUSIONS
In dialysis patients, rhIGF-I administration at a moderate dose has no protein metabolic effect, but the association with a moderate dose of rhGH is followed by a significant anabolic response.
Guebre-Egziabher
Fitsum
F
Department of Nephrology, Hôpital Edouard Herriot, 69437 Lyon Cedex 03, France. fitsum.guebre-egziabher@chu-lyon.fr
Juillard
Laurent
L
Boirie
Yves
Y
Laville
Martine
M
Beaufrère
Bernard
B
Fouque
Denis
D
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D006435:Renal Dialysis / Q000379:methods; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D001786:Blood Glucose; D004338:Drug Combinations; D018969:Insulin-Like Growth Factor Binding Proteins; D011506:Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone