IGF Binding Proteins in Growth-Retarded Children with Chronic Renal Failure

Abstract

ABSTRACT. Changes in the normal hormonal regulation of linear growth which lead to growth failure in children with chronic renal failure (CRF) are not well understood. Previous studies indicate that serum levels of growth hormone and IGF-I and I1 are normal or elevated in this population; and that serum levels of poorly defined inhibitors of IGF action are increased. Using a recently developed RIA for the 25-kD IGF-binding protein (IGF-BP25), we report significant elevations of this protein in children with CRF when compared to age-and sex-matched controls. IGF-BP25 levels correlate positively with IGF-binding activity in both populations, indicating that the RIA reflects levels of bioactive protein. Although the variation of serum IGF-BP25 with chronologic age and IGF levels are preserved in CRF, the quantitative interrelationships are disrupted. Levels of the 53-kD IGF-binding protein, an IGFbinding protein derived from the high mol wt IGF complex, were also found to be elevated in the CRF population and, unlike in the control population, did not vary with age or IGF levels. IGF-BP25 has been shown to inhibit IGF mitogenic action in vitro. Our finding of elevated levels of IGF-BP25 in children with CRF suggests that this protein may play a role in the growth retardation of pediatric chronic renal failure. The significance of the elevated IGF-BP53 levels in CRF remains uncertain. (Pediatr Res 26:308-315, 1989)

Characterization of Insulin-Like Growth Factor Binding Protein-3 in Chronic Renal Failure Serum

“…The finding that CRF adolescents have high serum IGFBP-1 levels by immunoprecipitation and by ligand blot is consistent with high IGFBP-1 levels found in this same serum by RIA and is also consistent with past reports of high RIA levels of IGFBP-1 in serum from CRF children and adults (19,33,39,40). In the present study, IGFBP-I levels are '/60 of the levels of IGFBP-3 in serum of CRF adolescents.…”

“…using the same antiserum as was used for immunoprecipitation; radioligand consisted of [12SI]IGF-I covalently bound to IGFBP-3 (34). The IGFBP-I RIA was also performed as described previously, using antiserum raised to human IGFBP-I purified from human HEP G2 cells ( 19).…”

“…In past studies, we have also found by RIA that serum IGFBP-3 levels are high in CRF children ( 19). However.…”

Changes in Serum Levels of IGF-I and IGFBP-3 in Children with Chronic Renal Failure.

“…More than 95% of serum IGF-I and II are bound to IG-FBP-3 and the acid labile subunit [11]. Serum IGFBP-3 levels might reflect increased IGF-binding activity, that may decrease free IGF-I levels and growth retardation in uremia [1,3,12].…”

“…Second, abnormal IGF generation may be responsible for impaired growth in uremia, because GH is thought to stimulate skeletal growth indirectly through the generation of IGFs. Insulin-like growth factor (IGF)-I and IGF-II are low molecular weight peptides that mediate the mitogenic actions of growth hormone [3]. IGF-I is the major growth factor involved in postnatal growth [4].…”