Effects of IGF-I on renal function in end-stage chronic renal failure

To determine whether insulin-like growth factor I (IGF-I) affects kidney function in patients with end-stage chronic renal failure, we administered recombinant human IGF-I (rhIGF-I) (100 micrograms/kg body wt subcutaneously twice daily) to nine individuals with baseline inulin clearances below 21 ml/min/1.73 m2. Four patients were treated for four days (short-term treatment) and five for periods between 13 and 27 days (long-term treatment). Administration of rhIGF-I increased inulin clearance, p-aminohippurate (PAH) clearance and the percent tubular reabsorption of filtered phosphate, and decreased plasma creatinine, blood urea nitrogen (BUN) and plasma phosphate during short-term administration. Kidney volume was unchanged in patients receiving the growth factor. rhIGF-I did not cause weight gain, proteinuria or hypoglycemia. Inulin clearance was not increased significantly above baseline after 13 or 20 days of IGF-I administration. PAH clearance remained elevated after 13 days, but not after 20 days of IGF-I. Levels of total circulating IGF-I were elevated above basal levels during the entire course of long-term IGF-I administration. In contrast, levels of circulating IGF binding protein 3 (IGFBP3) declined over time. Side effects related to IGF-I forced discontinuation of its use in two of five patients undergoing long-term treatment, and side-effects possibly related to IGF-I prompted discontinuation of its use in two others. We conclude that rhIGF-I can enhance glomerular filtration rate and renal plasma flow when administered short-term to humans with end-stage chronic renal renal failure. Further studies will be required to define its efficacy and usefulness long-term.