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Growth hormone for children with chronic renal failure
D Vimalachandra1, J C Craig, C Cowell
1Centre for Kidney Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, Australia, 2145. dushyann@chw.edu.au
Insights
Recombinant human growth hormone (hGH) treatment significantly increases height velocity in children with chronic renal failure (CRF) within one year. However, its effect on final adult height remains uncertain, warranting further research into longer or higher-dose treatments.
Area of Science:
- Pediatric Nephrology
- Endocrinology
- Clinical Trials Methodology
Background:
- Chronic renal failure (CRF) in children can impair growth.
- Recombinant human growth hormone (hGH) is a potential therapeutic intervention for growth deficits.
Purpose of the Study:
- To systematically evaluate the efficacy and safety of hGH treatment in children with CRF.
- To synthesize evidence from randomized controlled trials (RCTs) on height outcomes and adverse effects.
Main Methods:
- A comprehensive search of multiple databases and expert contact identified 10 RCTs.
- Studies included children aged 0-18 with CRF, comparing hGH to placebo/no treatment or different hGH doses.
- Primary outcome was change in height standard deviation score (SDS); secondary outcomes included height velocity, final height, and quality of life.
Main Results:
- One year of hGH (28 IU/m²/wk) significantly increased height SDS (WMD 0.77) and height velocity (WMD 4.1 cm/yr).
- Higher hGH dose (28 vs. 14 IU/m²/wk) showed an additional 1.4 cm/yr increase in height velocity.
- No further height gains were observed in the second year; side effect frequencies were similar to controls.
Conclusions:
- One year of hGH treatment demonstrably improves height velocity in children with CRF.
- The impact of hGH on achieving final adult height requires further investigation.
- Optimal treatment duration and dosage for maximizing growth benefits in pediatric CRF patients need additional study.
Objectives:
To evaluate the benefits and harms of recombinant human growth hormone (hGH) treatment in children with chronic renal failure (CRF).
Search Strategy:
Published and unpublished randomised controlled trials (RCTs) were identified from the Cochrane Controlled Trials Register, Medline, Embase, article reference lists and through contact with local and international experts in the field.
Selection Criteria:
Randomised controlled trials (RCTs) were included if they were carried out in children aged 0-18 years, diagnosed with CRF who are pre-dialysis, on dialysis or post-transplant; if they compared hGH treatment with placebo/no treatment or two doses of hGH treatments; and if they included height outcomes.
Data Collection And Analysis:
Two reviewers independently assessed studies for methodological quality and extracted data from eligible trials. The primary outcome measure was difference in mean change in height standard deviation score (SDS). Secondary outcome measures included change in height SDS from treatment onset to completion, change in height SDS during puberty, change in height velocity, final height, quality of life and adverse effects. To estimate summary treatment effects, data was pooled using a random effects model with calculation of weighted mean difference (WMD) for continuous outcomes and relative risk for categorical outcomes.
Main Results:
Ten RCTs involving 481 children were identified. Treatment with hGH (28 IU/m(2)/wk) resulted in a significant increase in height standard deviation score (SDS) at one year (four trials, WMD0.77, 95% confidence limits (CI) 0.51 to 1.04), and a significant increase in height velocity at six months (two trials, WMD 5.7 cm/yr, 95%CI 4.4 to 7.0) and one year (two trials, WMD 4.1 cm/yr, 95%CI 2.6 to 5.6), but there was no further increase in height indices during the second year of administration. Compared to the 14 IU/m(2)/wk group, there was a 1.4 cm/yr (0.6 to 2.2) increase in height velocity in the 28 IU/m(2)/wk group. The frequency of reported side effects of hGH were similar to that of the control group.
Reviewer'S Conclusions:
On average, one year of 28 IU/m(2)/wk hGH in children with CRF results in a 4 cm/yr increase in height velocity above that of untreated controls, however, it is not certain if this will result in an increase in final adult height. Benefits of longer courses or higher doses of treatment warrants further study.