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

Abstract

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