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  • Title: Effect of chronic renal failure and growth hormone therapy on the insulin-like growth factors and their binding proteins.
    Author: Powell DR, Liu F, Baker BK, Hinzt RL, Kale A, Suwanichkul A, Durham SK.
    Journal: Pediatr Nephrol; 2000 Jul; 14(7):579-83. PubMed ID: 10912522.
    Abstract:
    Children with chronic-renal failure (CRF) are often growth retarded, and abnormalities of the growth hormone (GH)/insulin-like growth factor (IGF) axis in CRF may contribute to this poor growth. Despite normal IGF levels in CRF serum, IGF bioactivity is low due to excess IGF-binding proteins (IGFBPs) in the 35-kDa serum fractions. Levels of IGFBP-1, -2, -4 and -6, and a 29-kDa IGFBP-3 fragment, are high in CRF serum, and levels of intact IGFBP- 1 and -2 correlate negatively with height. IGFBP-1 levels may be high due to insulin resistance, suggesting that the FKHR family of transcription factors may play a role in the overexpression of IGFBP-1, and other growth inhibitors, in CRF. GH-treated CRF children show catch-up growth that correlates positively with a rise in each component of the 150-kDa serum ternary complex (IGF-I or -II/IGFBP-3 or -5/acid-labile subunit); IGFBP-1, -2 and -6 levels do not rise, but serum IGF bioactivity does. Thus, GH increases levels of IGFs and ternary complexes in CRF serum. It is likely that increased IGFs contribute to catch-up growth by overcoming the inhibitory effects of excess IGFBPs present in the CRF milieu.
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