Effects of renal failure on the growth hormone-insulin-like growth factor axis

Abstract

Children with chronic renal failure (CRF) often have retarded growth, and abnormalities of the growth hormone-insulin-like growth factor (GH-IGF) axis in CRF may contribute to this growth failure. The serum GH and IGF levels are normal in these children, but IGF bioactivity is low as a result of excess IGF binding proteins (IGFBPs) in the 35 kd serum fractions. The levels of intact IGFBP-1, -2, and -6 and of a 29 kd IGFBP-3 fragment are all high, and the IGFBP-1 and -2 levels correlate negatively with height. Children with CRF who are treated with GH show catch-up growth that correlates positively with the increase in each component of the 150 kd serum ternary complex (acid-labile subunit, IGFBP-3, IGF-I, and IGF-II). Consistent with this observation, the increase in IGFBP-3 levels is confined to the 150 kd serum fractions. Serum levels of IGFBP-1, -2, and -6 do not rise, but serum IGF bioactivity does. Thus GH appears to induce an increase in the ternary complex in the serum of children with CRF. It is possible that IGFs released by the 150 kd serum complex promote growth by overcoming the inhibitory effects of excess IGFBPs in the 35 kd serum fractions.