IMPAIRED METABOLIC RESPONSE TO RECOMBINANT INSULIN-LIKE GROWTH-FACTOR-I IN DIALYSIS PATIENTS

The acute metabolic effects of recombinant human insulin-like growth f actor-1 (rhIGF-1) were studied after an overnight fast in six maintena nce hemodialysis (MHD) patients, six chronic peritoneal dialysis (PD) patients and six normal subjects. Each subject received a subcutaneous injection of rhIGF-1, 50 or 100 mu g/kg body wt, given in random orde r on two occasions separated by 7 to 21 days. After the rhIGF-1 inject ion, plasma insulin, C-peptide, cortisol, amino acids and glucose decr eased. The magnitude of the decrease was greater with the larger rhIGF -1 dose. The fall in plasma insulin, C-peptide and many amino acid con centrations was less and the decrease in glucose was similar in the MH D and CAPD patients as compared to normals. With 50 mu g rhIGF-1/kg, p lasma insulin and C-peptide decreased more quickly and often to a grea ter magnitude in normal individuals. With 100 mu g rhIGF-1/kg, the dec rease in plasma insulin, C-peptide and amino acids in the MHD and CAPD patients was almost as frequent as in the normal subjects, but the ma gnitude of the fall was often significantly less. This impaired respon se occurred in both MHD and CAPD patients even though, with the 100 mu g rhIGF-1/kg dose, their plasma IGF-1 was significantly higher than i n normals during most of the first four hours after injection. These r esults provide the first in vivo evidence for resistance to the metabo lic effects of rhIGF-1 in patients with advanced renal failure.