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Short-Term Administration of a Combination of Recombinant Growth Hormone and Insulin-Like Growth Factor-I Induces Anabolism in Maintenance Hemodialysis

Department of Nephrology (F.G.-E., L.J., D.F.), Hôpital Edouard Herriot, 69437 Lyon, France; Institut National de la Santé et de la Recherche Médicale Unité 870, University Claude Bernard Lyon 1, 69372 Lyon, France; Centre de Recherche en Nutrition Humaine de Lyon (F.G.-E., M.L., D.F.), 69437 Lyon, France; and Centre de Recherche en Nutrition Humaine (Y.B., B.B.), 63009 Clermont-Ferrand, France

Address all correspondence and requests for reprints to: Dr. Fitsum Guebre-Egziabher, Department of Nephrology, Hôpital Edouard Herriot, 69437 Lyon Cedex 03, France. E-mail: fitsum.guebre-egziabher{at}chu-lyon.fr.

Context: 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.

Design: 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 µg/kg per 12h) with an association of rhIGF-I + rhGH (50 µg/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.