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Pathogenic mechanisms underlying the variable response to recombinant human growth hormone in children with chronic
1Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
Insights
Children with chronic renal failure (CRF) show less height gain with recombinant human growth hormone (rhGH) as kidney function declines. This response is linked to somatotropic hormone axis abnormalities, not just CRF complications.
Area of Science:
- Pediatric Nephrology
- Endocrinology
- Growth Hormone Therapy
Background:
- Children with chronic renal failure (CRF) often experience growth failure.
- Recombinant human growth hormone (rhGH) is used to stimulate growth in these children.
- The effectiveness of rhGH therapy can vary significantly based on the severity of renal dysfunction.
Purpose of the Study:
- To investigate the relationship between the degree of renal dysfunction and height gain in children with CRF treated with rhGH.
- To determine if secondary complications of CRF explain the reduced response to rhGH in end-stage renal failure.
- To identify underlying mechanisms related to the somatotropic hormone axis that influence rhGH treatment outcomes.
Main Methods:
- Analysis of height gain in children with CRF undergoing rhGH therapy.
- Correlation of growth response with the degree of renal dysfunction (glomerular filtration rate).
- Assessment of secondary complications of CRF (metabolic acidosis, anemia, hyperparathyroidism) and their impact on growth.
Main Results:
- Height gain from rhGH treatment is inversely related to the degree of renal dysfunction in children with CRF.
- Secondary complications of CRF do not fully account for the diminished rhGH response in end-stage renal failure.
- Abnormalities of the somatotropic hormone axis, including partial GH receptor deficiency, increased IGF-I binding, and IGF-I action inhibitors, correlate with renal dysfunction and reduced rhGH efficacy.
Conclusions:
- The response to rhGH in children with CRF is significantly influenced by the severity of renal dysfunction.
- Somatotropic hormone axis derangements are key factors explaining the variable response to rhGH in pediatric chronic renal failure.
- Optimizing growth promotion in end-stage renal failure requires understanding the specific contributions of these hormonal alterations to uremia.
Abstract:
As with spontaneous growth, the height gain achieved by stimulation with recombinant human growth hormone (rhGH) in children with chronic renal failure appears to be inversely related to the degree of renal dysfunction. The secondary complications of CRF that may independently interfere with growth, such as metabolic acidosis, anaemia, and secondary hyperparathyroidism, do not explain the poorer response to rhGH in children with end-stage renal failure. Certain abnormalities of the somatotropic hormone axis, the severity of which is related to the degree of renal dysfunction, are more likely to explain the dependence of the rhGH treatment response on glomerular filtration rate. These derangements include partial GH receptor deficiency, increased plasma binding of IGF-I, and accumulation of non-competitive inhibitors of IGF-I action. Strategies to optimise growth-promoting treatment in end-stage renal failure will depend on the relative contribution of these different somatotropic hormone axis alterations to uraemia.