Insulin-like growth factor-I treatment to enhance renal function in advanced chronic renal failure.
Because of the potential for IGF-I to enhance renal function in advanced chronic renal failure (CRF) we set out to determine whether IGF-I 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-I and then we examined the effect of prolonged IGF-I treatment on the renal function of patients with an average GFR of 17 mL/min/1.73 m2. Interestingly the metabolic clearance rate of IGF-I in CRF subjects was similar to that in normal subjects even though the total serum IGF-I levels rose to higher maximum levels. This increase was due to a reduced volume of IGF-I 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 PAH 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-I therapy. Adverse effects were mild, of short duration and easily manageable. Thus IGF-I pharmacokinetics are largely unchanged in CRF and the administration of IGF-I produces a modest improvement in the GFR. These results appear to justify more extensive examination of the therapeutic role of IGF-I in the treatment of CRF.
Fervenza
F C
FC
Medicine Service Veterans Affairs, Palo Alto Health Care System, California, USA.
Friedlaender
M M
MM
Ike
J O
JO
Rabkin
R
R
D000328:Adult; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D003404:Creatinine / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007444:Inulin / Q000378:metabolism; D007668:Kidney / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D011994:Recombinant Proteins
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D007444:Inulin; D003404:Creatinine