IGF-I and its variant, des-(1-3)IGF-I, enhance growth in rats with reduced renal mass

Abstract

The efficacy of insulin-like growth factor I (IGF-I) in enhancing growth in animals with reduced renal mass was investigated in subtotally nephrectomized young male rats. Recombinant human IGF-I was administered by osmotic minipumps for 7 days at two doses, 0.9 and 2.2 mg.kg body wt-1. day-1, and the truncated analogue of IGF-I, des-(1-3)IGF-I, was given at a dose of 0.9 mg.kg body wt-1.day-1. The partial nephrectomy procedure resulted in significantly impaired renal function as evidenced by elevated serum urea and creatinine concentrations, reduced creatinine clearance, and increased average daily urine output. Carcass composition was significantly altered in animals with reduced renal mass; water content increased and fat content decreased, while protein content remained unchanged. Carcass composition was not affected by IGF treatment. Body weight gain, food utilization, and nitrogen balance during the treatment period were significantly increased in rats treated with IGF-I at both the lower and higher doses and in those treated with des-(1-3)IGF-I. The improved nitrogen balance in the des-(1-3)IGF-I group could at least partly be explained by a diminished rate of muscle protein breakdown, as indicated by the reduced urinary excretion rate of 3-methylhistidine. Compensatory hypertrophy of the remnant kidney was significantly increased in the group treated with the high dose of IGF-I. These results suggest that IGF-I may have beneficial effects on somatic growth and nitrogen balance in renal insufficiency, with des-(1--3)IGF-I being particularly effective in reducing the rate of muscle protein breakdown.