Characterization of insulin-like growth factor binding protein-3 in chronic renal failure serum

IGF-binding protein-3 (IGFBP-3), usually found as glycosylated 41- and 38-kD forms, is the major serum IGFBP during extrauterine life. In normal serum IGFBP-3 binds one IGF peptide and one acid-labile (alpha) subunit in a high-molecular-weight (MW) complex of 150 kD. By RIA, an excess of IGFBP-3 is present in chronic renal failure (CRF) serum, where it reportedly accumulates at low MW (25-55 kD) rather than as part of the 150-kD complex. To further evaluate IGFBP-3 forms in CRF, sera were obtained from seven healthy adolescents and seven adolescents with CRF. By RIA, IGFBP-3 levels were higher in CRF than normal sera (15.4 +/- 2.2 versus 10.1 +/- 2.1 micrograms/mL). High-MW (150-kD) fractions of CRF and normal sera, obtained by neutral size-exclusion chromatography, had equal amounts of IGFBP-3 by RIA. However, a second RIA peak of IGFBP-3, present in low-MW (35-kD) fractions of CRF but not normal sera, could account for the higher IGFBP-3 levels of CRF serum. [125I]IGF ligand blots of whole serum and serum fractions, either with or without prior precipitation by IGFBP-3 antiserum, found levels of 41- and 38-kD IGFBP-3 forms to be similar between CRF and normal whole sera and located these forms in the high-MW (150-kD) fractions of CRF and normal sera.(ABSTRACT TRUNCATED AT 250 WORDS)