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Growth failure in renal disease
Insights
Children with chronic renal failure (CRF) experience impaired growth, particularly during infancy and puberty, due to malnutrition and hormonal issues. Recombinant human growth hormone (rhGH) treatment shows promise in improving growth velocity across all disease stages.
Area of Science:
- Pediatric Nephrology
- Endocrinology
- Growth and Development
Background:
- Children with chronic renal failure (CRF) exhibit significant height loss, primarily during infancy and puberty.
- Growth impairment in CRF stems from malnutrition, metabolic disturbances in early life, and hormonal dysregulation, including growth hormone (GH) resistance, during puberty.
Purpose of the Study:
- To investigate the factors contributing to growth impairment in children with CRF.
- To evaluate the efficacy of recombinant human growth hormone (rhGH) therapy in improving growth in pediatric CRF patients.
Main Methods:
- Analysis of growth patterns during infancy and puberty in CRF patients.
- Assessment of hormonal profiles, including GH secretion, half-life, and insulin-like growth factor (IGF) system components.
- Evaluation of rhGH treatment outcomes, including growth velocity and height changes.
Main Results:
- CRF leads to delayed puberty, reduced growth velocity, and diminished peak height velocity.
- GH resistance is evident in CRF, characterized by normal GH secretion but prolonged half-life and reduced IGF-I bioactivity due to altered IGF binding proteins (IGFBPs).
- rhGH therapy (1 IU/kg/week) significantly improves growth velocity, with a mean height increase of +1.5 SDS in prepubertal children over two years.
Conclusions:
- Growth impairment in pediatric CRF is multifactorial, involving nutritional, metabolic, and endocrine factors.
- rhGH treatment is effective in enhancing growth velocity in children with CRF, irrespective of disease stage.
- Further research is needed to determine the long-term effects of rhGH on final height and its efficacy during puberty in CRF patients.
Abstract:
Children with congenital CRF lose height potential mainly during two distinct growth periods; infancy and puberty. The onset of puberty is late, the pubertal growth spurt starts from a very low rate of growth velocity, and peak height velocity is lower than normal although the absolute increment of height velocity is comparable to the increment in normal children. Furthermore, the duration of pubertal growth spurt is reduced in CRF. During infancy and early childhood, malnutrition, electrolyte disturbances and metabolic acidosis are the main contributing factors for reduced growth, whereas hormonal disturbances are responsible for growth impairment during puberty. There is evidence for resistance to growth hormone in CRF, which starts in early childhood and persists until the end of puberty. Growth hormone secretion is normal in CRF, but GH half-life is prolonged. The binding activity of the stable growth hormone binding protein is reduced, which points to a low receptor expression in the liver. Hepatic IGF-I production is diminished. However, the serum concentration of IGF binding proteins (IGFBP) is increased due to reduced renal filtration of low molecular weight subunits of IGFBP. Mainly, the accumulation of IGFBP-3 leads to increased IGF-binding capacity of the uraemic serum. Both, reduced IGF-I production and increased binding of IGF to IGFBP-3 result in decreased IGF bioactivity. During infancy, loss of growth potential can be prevented by adequate nutrition. Later in life, catch-up growth cannot be induced by nutritional intervention or dialysis. Renal transplantation allows catch-up growth in only a small percentage of patients. Treatment with one IU rhGH/kg/week improves growth velocity and growth in all stages of renal disease. The mean increment of height in prepubertal children is +1.5 SDS within two treatment years. The effect of rhGH during puberty as well as the effect on final height remain to be determined.