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 ab normalities of the growth hormone (GH)/insulin-like growth factor (IGF) axi s in CRF may contribute to this poor growth. Despite normal IGF levels in C RF 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 factor s may play a role in the overexpression of IGFBP-1, and other growth inhibi tors, in CRE GH-treated CRF children show catch-up growth that correlates p ositively with a rise in each component of the 150-kDa serum ternary comple x (IGF-I or -II/IGFBP-3 or -5/acid-labile subunit); IGFBP-1, -2 and -6 leve ls do not rise, but serum IGF bioactivity does. Thus, GH increases levels o f IGFs and ternary complexes in CRF serum. It is likely that increased IGFs contribute to catch-up growth by overcoming the inhibitory effects of exce ss IGFBPs present in the CRF milieu.