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Insulin-like growth factor binding proteins as growth inhibitors in children with chronic renal failure
1Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Insights
Children with chronic renal failure (CRF) experience growth failure due to inhibited insulin-like growth factor-I (IGF-I) action. Elevated insulin-like growth factor binding proteins (IGFBPs) in their serum likely contribute to this condition.
Area of Science:
- Pediatric Nephrology
- Endocrinology
- Growth Hormone Axis Research
Background:
- Children with chronic renal failure (CRF) often exhibit impaired growth, failing to reach their genetic height potential.
- The growth hormone (GH)/insulin-like growth factor (IGF)/growth plate chondrocyte axis is implicated in this growth failure.
- Hepatic GH resistance may lead to reduced IGF-I expression, but serum IGF-I levels are typically normal, suggesting impaired IGF-I action.
Purpose of the Study:
- To evaluate the roles of specific insulin-like growth factor binding proteins (IGFBPs), namely IGFBP-1, IGFBP-2, and IGFBP-3, as potential growth inhibitors in children with CRF.
- To investigate the contribution of these IGFBPs to the overall inhibition of IGF-I action observed in CRF.
Main Methods:
- Serum samples from children with CRF were analyzed to assess levels and potential inhibitory roles of IGFBP-1, IGFBP-2, and IGFBP-3.
- The study evaluated the criteria for each IGFBP acting as a growth inhibitor in the context of CRF.
Main Results:
- Data suggest that IGFBP-1, IGFBP-2, and IGFBP-3 each play a role in inhibiting growth in children with CRF.
- IGFBP-1 currently meets most criteria expected of a growth inhibitor in this population.
- IGFBP-2 and IGFBP-3 are also likely contributors to growth failure in CRF.
Conclusions:
- Elevated levels of IGFBPs in CRF serum contribute to excess high-affinity IGF binding sites, inhibiting IGF-I action.
- IGFBP-1, IGFBP-2, and IGFBP-3 are implicated as significant contributors to the growth failure observed in children with chronic renal failure.
- Further research may reveal that multiple IGFBPs collectively contribute to the growth impediment in CRF.
Abstract:
Children with chronic renal failure (CRF) often fail to attain an adult height consistent with their genetic potential. The growth hormone (GH)/insulin-like growth factor (IGF)/growth plate chondrocyte axis has been intensively studied in these children to determine the basis for this growth failure. Evidence suggests that hepatic GH resistance results in deficient expression of IGF-I. However, serum IGF-I levels are usually normal and it is IGF-I action on target tissues which is inhibited, possibly by the presence of excess high-affinity IGF binding proteins (IGFBPs) in CRF serum. In this paper we evaluate the roles of IGFBP-1, -2, and -3 as growth inhibitors in CRF children. The data support a role for each of these IGFBPs as growth inhibitors. Currently, IGFBP-1 meets most criteria expected of a growth inhibitor, but IGFBP-2 and -3 will likely also meet these criteria and may well be important contributors to the growth failure of CRF. Ultimately, many or all of the six IGFBPs may be found to contribute to the excess high-affinity IGF binding sites which are a hallmark of CRF serum and are possible contributors to the growth failure of CRF children.