EFFECTS OF CHRONIC-RENAL-FAILURE ON PLASMA-CLEARANCE OF INSULIN-LIKE GROWTH-FACTOR-I, DES-(1-3)IGF-I, AND LR(3)IGF-I

Using a rat model of chronic renal failure (CRF), we examined insulin- like growth factor I(IGF-I) clearance, degradation, organ distribution , and IGF binding profiles in plasma. The effects of IGF-binding prote ins (IGFBP) on IGF clearance and degradation in CRF were studied using the IGF-I analogues des-(1-3)IGF-I and LR(3)IGF-I, which bind poorly to IGFBP. Although total clearance of IGF-I was not significantly alte red in CRF, half-life and area under the curve were increased in the r apid distribution phase and were reduced in the slow elimination phase . Total clearance of LR(3)IGF-I was significantly increased. Reduced b inding of IGF-I in the 150-kDa complex and increased binding to smalle r-molecular-weight IGFBP were observed in CRF. Increased degradation o f both IGF-I and LR(3)IGF-I was associated with reduced IGF binding in the 150-kDa complex. The results suggest that the accumulation of low er-molecular-weight IGFBP with reduced IGF binding in the 150-kDa comp lex, associated with increased degradation of peptide, may explain, at least in part, the reduced bioactivity of IGF-I observed in CRF.