title: The insulin-like growth factor axis and growth in children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.
abstract: Children with chronic renal failure (CRF) are often growth recarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35-kDa fractions of CRF serum contribute to CRF growth failure. This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP-3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150-kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. dpowell@bcm.tmc.edu
authors.forename: D R
authors.initials: DR
authors.lastname: Powell
authors.forename: S K
authors.initials: SK
authors.lastname: Durham
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: B K
authors.initials: BK
authors.lastname: Baker
authors.forename: P D
authors.initials: PD
authors.lastname: Lee
authors.forename: S L
authors.initials: SL
authors.lastname: Watkins
authors.forename: P G
authors.initials: PG
authors.lastname: Campbell
authors.forename: E D
authors.initials: ED
authors.lastname: Brewer
authors.forename: R L
authors.initials: RL
authors.lastname: Hintz
authors.forename: R J
authors.initials: RJ
authors.lastname: Hogg
mesh_terms: D002648:Child; D002675:Child, Preschool; D002850:Chromatography, Gel; D005260:Female; D006128:Growth; D019382:Human Growth Hormone / Q000097:blood* / Q000627:therapeutic use*; D006801:Humans; D015151:Immunoblotting; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II