Clinical Investigation

Kidney International (1995) 47, 876–883; doi:10.1038/ki.1995.131

Impaired metabolic response to recombinant insulin-like growth factor-1 in dialysis patients

Denis Fouque1, Susy C Peng and Joel D Kopple

Department of Medicine, Harbor-UCLA Medical Center, Torrance, and the UCLA Schools of Medicine and Public Health, Los Angeles, California, USA

Correspondence: Joel D Kopple MD, Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, 1000 W. Carson Street, Torrance, California 90501, USA.

1Present address: Department of Nephrology, University Claude Bernard and Hôpital Edouard Herriot, Lyon, France.

Received 24 January 1994; Revised 15 October 1994; Accepted 15 October 1994.

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Abstract

Impaired metabolic response to recombinant insulin-like growth factor 1 in dialysis patients. The acute metabolic effects of recombinant human insulin-like growth factor-1 (rhIGF-1) were studied after an overnight fast in six maintenance 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 microg/kg body wt, given in random order on two occasions separated by 7 to 21 days. After the rhIGF-1 injection, plasma insulin, C-peptide, Cortisol, amino acids and glucose decreased. The magnitude of the decrease was greater with the larger rhIGF-1 dose. The fall in plasma insulin, C-peptide and many amino acid concentrations was less and the decrease in glucose was similar in the MHD and CAPD patients as compared to normals. With 50 microg rhIGF-1/kg, plasma insulin and C-peptide decreased more quickly and often to a greater magnitude in normal individuals. With 100 microg rhIGF-1/kg, the decrease 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 magnitude of the fall was often significantly less. This impaired response occurred in both MHD and CAPD patients even though, with the 100 microg rhIGF-1/kg dose, their plasma IGF-1 was significantly higher than in normals during most of the first four hours after injection. These results provide the first in vivo evidence for resistance to the metabolic effects of rhIGF-1 in patients with advanced renal failure.

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