Insulin-Like Growth Factor–I Treatment to Enhance Renal Function in Advanced Chronic Renal Failure

Abstract

Because of the potential for IGF-1 to enhance renal function in advanced chronic renal failure (CRF) we set out to determine whether IGF-1 can induce a sustained increase in renal function in patients with near end-stage renal failure. To this end we first examined the impact of CRF on the pharmacokinetics of IGF-1 and then we examined the effect of prolonged IGF-I treatment on the renal function of patients with an average GFR of 17mL/min/1.73m2. Interestingly the metabolic clearance rate of IGF-1 in CRF subjects was similar to that in normal subjects even though the total serum IGF-1 levels rose to higher maximum levels. This increase was due to a reduced volume of IGF-1 distribution, a consequence of the elevated serum IGF binding proteins in CRF subjects. Treatment with IGF-I (60 mg/kg twice daily sc) for 31 days resulted in a 14% and 18% increase in the inulin and PAIL clearances respectively (n = 6 patients). These parameters returned to basal levels on stopping treatment. Serum immunoreactive IGFBP-3 levels fell and IGFBP-2 and -3 levels rose during IGF-1 therapy. Adverse effects were mild, of short duration and easily manage-able. Thus IGF-I pharmacokinetics are largely unchanged in CRF and the administration of IGF-1 produces a modest improvement in the GFR. These results appear to justify more extensive examination of the therapeutic role of IGF-1 in the treatment of CRF.