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IGF binding proteins in growth-retarded children with chronic renal failure
P D Lee1, R L Hintz, J B Sperry
1Diabetes Research Center, Baylor College of Medicine, Houston, Texas 77054.
Insights
Children with chronic renal failure (CRF) exhibit elevated levels of insulin-like growth factor-binding protein 25 (IGF-BP25), a protein known to inhibit growth. This suggests IGF-BP25 may contribute to growth failure in pediatric CRF.
Area of Science:
- Pediatric Nephrology
- Endocrinology
- Growth Regulation
Background:
- Children with chronic renal failure (CRF) often experience growth failure.
- Hormonal regulation of linear growth in pediatric CRF is not fully understood.
- Previous studies suggest elevated inhibitors of insulin-like growth factor (IGF) action in CRF.
Purpose of the Study:
- To investigate the role of specific IGF-binding proteins in the growth retardation associated with pediatric CRF.
- To quantify levels of IGF-binding protein 25 (IGF-BP25) and IGF-binding protein 53 (IGF-BP53) in children with CRF.
Main Methods:
- Utilized a newly developed radioimmunoassay (RIA) to measure serum IGF-BP25 levels.
- Compared IGF-BP25 and IGF-BP53 levels in children with CRF to age- and sex-matched controls.
- Assessed correlations between IGF-binding protein levels, IGF-binding activity, age, and IGF levels.
Main Results:
- Children with CRF showed significantly elevated serum levels of IGF-BP25 compared to controls.
- Elevated IGF-BP53 levels were also observed in the CRF population.
- While IGF-BP25 levels correlated with IGF-binding activity, their quantitative interrelationships with age and IGF levels were disrupted in CRF.
Conclusions:
- Elevated IGF-BP25 in pediatric CRF suggests a potential role in growth retardation.
- The increased IGF-BP25 may inhibit IGF action, contributing to poor linear growth.
- The clinical significance of elevated IGF-BP53 in pediatric CRF requires further investigation.
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 II 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 IGF-binding 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.