title: Insulin-like growth factor-I and insulin-like growth factor-binding proteins in the nephrotic syndrome.
abstract: Similar to findings in the nephrotic syndrome in humans, rats with the doxorubicin-induced nephrotic syndrome (which resembles minimal change disease) have reduced serum levels of insulin-like growth factor-I (IGF-I). This is mainly caused by glomerular ultrafiltration of IGF-I-containing binding protein complexes, primarily of a molecular weight of approximately 50 kilodaltons, and urinary losses of the peptide. Despite urinary excretion of IGF-binding protein (IGFBP)-2, serum levels are increased more than twofold in the nephrotic syndrome compared with controls, because of increased synthesis of this binding protein by the liver. In contrast, the liver synthesis of IGFBP-3, the predominant binding protein in normal serum, is unchanged in the nephrotic syndrome. However, binding and serum levels of IGFBP-3 are reduced in nephrotic rat serum, apparently due to proteolytic degradation of IGFBP-3. The glomerular ultrafiltration of IGF-I, which leads to biologically significant IGF-I concentrations of about 1.35 nM in proximal tubule fluid, may have metabolic consequences, such as increased tubular phosphate absorption. Hypothetically, tubule fluid IGF-I may also contribute to progressive tubulointerstitial fibrosis which is sometimes present in protractive nephrotic glomerulopathies. The profound changes in the IGF-I/IGFBP system in the nephrotic syndrome may also contribute to systemic metabolic abnormalities and growth failure.
authors.affiliation: Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance 90509, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Feld
authors.forename: R
authors.initials: R
authors.lastname: Hirschberg
mesh_terms: D000818:Animals; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009404:Nephrotic Syndrome / Q000097:blood*; D051381:Rats
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I