Effect of chronic renal failure and growth hormone therapy on the insulin-like growth factors and their binding proteins

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...

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Bibliographic Details
Published in:Pediatric nephrology (Berlin, West) West), 2000-07, Vol.14 (7), p.579-583
Main Authors: Powell, D R, Liu, F, Baker, B K, Hinzt, R L, Kale, A, Suwanichkul, A, Durham, S K
Format: Article
Language:English
Subjects:
Animals
Biological activity
Child, Preschool
Endocrine therapy
Growth hormones
Growth Inhibitors - physiology
Human Growth Hormone - therapeutic use
Humans
Insulin resistance
Insulin-Like Growth Factor Binding Proteins - metabolism
Insulin-Like Growth Factor Binding Proteins - physiology
Insulin-like growth factors
Kidney Failure, Chronic - blood
Kidney Failure, Chronic - drug therapy
Pediatrics
Proteins
Recombinant Proteins - therapeutic use
Somatomedins - metabolism
Treatment Failure
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Summary: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.
ISSN:0931-041X
1432-198X
DOI:10.1007/s004670000349