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Growth hormone--insulin-like growth factor-I (IGF-I) axis in prepubertal children with chronic renal failure
J Ferraris1, T Pasqualini, R Gutman
1Departamento de Pediatría, Hospital Italiano, Buenos Aires, Argentina.
Insights
Children with chronic renal failure (CRF) and growth retardation show altered growth hormone (GH) secretion. Renal transplant patients exhibit reduced GH response influenced by glucocorticoids, impacting insulin-like growth factor I (IGF-I) levels.
Area of Science:
- Pediatric Endocrinology
- Nephrology
- Growth Hormone Axis
Background:
- Children with chronic renal failure (CRF) often experience growth retardation.
- The hypothalamic-pituitary insulin-like growth factor I (IGF-I) axis plays a crucial role in growth and development.
- Understanding growth hormone (GH) dynamics in pediatric CRF and post-renal transplantation is vital for optimizing growth outcomes.
Purpose of the Study:
- To evaluate the hypothalamic-pituitary IGF-I axis in children with CRF on dialysis versus those who have undergone renal transplantation.
- To investigate the impact of glucocorticoids on GH secretion and IGF-I levels in pediatric renal transplant recipients.
Main Methods:
- Assessed height standard deviation score (SDS), growth velocity, mean nocturnal GH, and GH pulse frequency in 12 children with CRF and 13 renal transplant patients.
- Administered GH releasing hormone (GHRH) tests to evaluate GH peak response and area under the curve.
- Correlated GH parameters and serum IGF-I levels with clinical factors including steroid treatment (deflazacort vs. methylprednisone) and transplant status.
Main Results:
- Children with CRF and growth retardation had a higher number of GH peaks and slightly elevated mean GH levels compared to transplant patients.
- Renal transplant patients exhibited significantly lower growth velocity (1.5 cm/year) compared to CRF patients (3.7 cm/year).
- GH response to GHRH was higher in CRF and transplant children on deflazacort versus those on methylprednisone; transplant patients showed a negative correlation between methylprednisone dose and IGF-I levels.
Conclusions:
- Pediatric CRF patients with growth retardation display distinct GH secretion patterns compared to transplant recipients.
- Glucocorticoid therapy, particularly methylprednisone, negatively impacts GH secretion and IGF-I levels in renal transplant patients.
- Deflazacort may offer a more favorable profile for GH axis function in post-transplant pediatric patients compared to methylprednisone.
Unlabelled:
The hypothalamic-pituitary insulin-like growth factor I (IGF-I) axis was evaluated in 12 children with chronic renal failure (CRF) aged 3.2 to 16.5 yr (mean 9.5) on chronic dialysis, and in 13 renal transplantation patients aged 7.5 to 15.0 yr (mean 11.1). Height standard deviation score (SDS) was -2.8 +/- 0.5 (mean +/- SE) and -3.0 +/- 0.3 SDS (p = NS), and growth velocity was 3.7 +/- 0.4 and 1.5 +/- 0.3 cm/year (p < 0.01), respectively. Mean nocturnal growth hormone (mean GH) and number of pulses > 5 ng/ml in CRF and transplantation children were 4.2 +/- 0.8 vs 2.4 +/- 0.3 ng/ml, p = 0.08 and 1.7 +/- 0.2 vs 1.0 +/- 0.2, p < 0.05, respectively. In transplant children there was a positive correlation between mean GH and growth velocity (p < 0.02). GH peak response and the area under the curve post GH releasing hormone test were significantly higher in CRF and transplant children treated with deflazacort (new steroid derived from prednisolone) vs transplant children treated with methylprednisone. Mean serum IGF-I levels were -0.5 +/- 0.2 SDS for chronological age (CA) in CRF patients and +0.8 +/- 0.2 SDS(CA) in transplant patients, p = NS. In the latter, serum IGF-I values were positively correlated with growth velocity (p < 0.02) and negatively correlated with methylprednisone dose (p < 0.05).
Conclusions:
Patients with CRF and growth retardation have a higher number of GH peaks and slightly elevated mean GH levels compared to transplant patients. After renal transplantation GH secretion may be influenced by glucocorticoids as shown by the lower GH response to GHRH which improved with deflazacort and the inverse correlation between methylprednisone dose and IGF-I levels.