Recombinant human insulin-like growth factor-1 induces an anabolic response in malnourished CAPD patients

Abstract

Insulin-like growth factor-1 (IGF-1) is an anabolic hormone that mediates most of the growth effects of growth hormone. This study tested the hypothesis that recombinant human IGF-1 (rhIGF-1) will induce an anabolic response in malnourished patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Six CAPD patients with protein-energy malnutrition underwent nitrogen balance studies in a clinical research center for 35 days each. Throughout the study, patients were maintained on their same CAPD regimen prior to hospitalization, and were fed a constant protein and energy intake that was similar to their diet prior to hospitalization. The first 15 hospital days were a baseline period; during the subsequent 20-day period, patients were given subcutaneous injections of rhIGF-1 (100 microg/kg/12 h), except for one patient who received 50 microg/kg/12 h for the first five days, followed by 100 microg/kg/12 h for the following 15 days. During the treatment with rhIGF-1, serum IGF-1 increased by about 100% (P = 0.03), and nitrogen balance became strongly positive (+2.0 g/day, P = 0.015 vs. baseline). This anabolic effect was observed within hours after commencing the rhIGF-1 treatment and was largely caused by a 20% decrease in peritoneal dialysate effluent nitrogen. There was a proportionate reduction in urine nitrogen and serum urea nitrogen. This decrease in nitrogen output was sustained during the entire 20 day of treatment with rhIGF-1. Serum phosphorus decreased significantly during the first several days of rhIGF-1 treatment, whereas serum calcium increased significantly during the rhIGF-1 treatment. Serum potassium and albumin did not change during the rhIGF-1 injections. There was no change in body weight and body composition, as assessed by anthropometry during the baseline or treatment phases of the study. Some patients exhibited minor possible adverse events that included a reduction in blood pressure and transient tachycardia. Injections of rhIGF-1 induce a strong and sustained anabolic effect, as indicated by a positive nitrogen balance in CAPD patients with protein-energy malnutrition. rhIGF-1 administration may be an effective method for treating malnutrition in maintenance dialysis patients.