Insulin-like growth factor I and its variant, des(1-3)IGF-I, improve nitrogen balance and food utilization in rats with renal failure.

The growth-promoting effects of IGF-I were examined in rats following partial nephrectomy and compared with the effects of the des(1-3) variant of IGF-I. Four groups of rats were subjected to 5/6 nephrectomy (n = 8 per group) and treated for 7 days with IGF-I (0.9 or 2.2 mg/kg BW/day), des(1-3)IGF-I (0.9 mg/kg/BW/day), or vehicle (0.1 M acetic acid) administered subcutaneously by osmotic pump. A group of vehicle-treated, sham-operated control rats (n = 7) was included. Food utilization was significantly improved in all three peptide-treated groups, by 13-16% compared with the vehicle-treated nephrectomized group. Also, nitrogen balance was enhanced, particularly in the des(1-3)IGF-I group, in which nitrogen excretion was reduced by 24%, with the low- and high-dose IGF-I groups showing 16 and 18% reductions, respectively. Serum urea levels were significantly decreased, by 25%, in the des(1-3)IGF-I group, with 20 and 17% reductions being observed in the low- and high-dose IGF-I groups. Muscle protein degradation was found to be significantly attenuated with des(1-3)IGF-I treatment but was not significantly affected in the two IGF-I-treated groups. While carcass composition was not altered with IGF peptide treatment, absolute mass of protein in the carcass was improved in rats treated with the high dose of IGF-I. These results show that IGF-I or, more particularly, des(1-3)IGF-I may be efficacious in overcoming impaired growth in renal failure.