THE INSULIN-LIKE-GROWTH-FACTOR AXIS AND GROWTH IN CHILDREN WITH CHRONIC-RENAL-FAILURE - A REPORT OF THE SOUTHWEST PEDIATRIC NEPHROLOGY STUDY-GROUP

Children with chronic renal failure (CRF) are often growth retarded de spite 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. Th is report characterizes the relationship between IGFBP-3 and IGF pepti des in the serum of growth-retarded CRF children. Size-exclusion chrom atography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 1 50-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 fractio ns 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. Treat ment of these CRF children with recombinant human GH increased the mol ar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amo unt 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 eff ects of these excess IGFBPs. Treatment with recombinant human GH incre ases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subseque nt IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF ser um.