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Growth hormone for children with chronic kidney disease
Elisabeth M Hodson1, Narelle S Willis, Jonathan C Craig
1Centre for Kidney Research, The Children’sHospital atWestmead,Westmead, Australia. Elisabeth.hodson@health.nsw.gov.au.
Insights
Recombinant human growth hormone (rhGH) significantly increases height velocity in children with chronic kidney disease (CKD). However, long-term effects on final adult height and potential adverse events require further investigation.
Area of Science:
- Pediatric Nephrology
- Endocrinology
- Clinical Trials
Background:
- Growth retardation is a common complication in children with chronic kidney disease (CKD).
- Recombinant human growth hormone (rhGH) is used to improve height in these children.
- Concerns exist regarding long-term benefits and potential adverse effects of rhGH therapy.
Purpose of the Study:
- To evaluate the benefits and harms of rhGH treatment in children with CKD.
- Assess the impact of rhGH on height outcomes in pediatric CKD patients.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials (RCTs).
- Included children aged 0-18 with CKD (pre-dialysis, dialysis, or post-transplant).
- Compared rhGH treatment with placebo/no treatment or different rhGH doses.
Main Results:
- Sixteen RCTs involving 809 children were analyzed.
- rhGH (28 IU/m²/wk) significantly increased height standard deviation score (HSDS) at one year (MD 0.82).
- Significant increases in height velocity were observed at six months (MD 2.85 cm/6 mo) and one year (MD 3.88 cm/y).
- Higher rhGH dose (28 IU/m²/wk) showed increased height velocity compared to lower dose (14 IU/m²/wk).
- Reported side effects were similar between rhGH and control groups.
Conclusions:
- One year of rhGH treatment significantly improves height velocity in children with CKD.
- Current studies are insufficient to determine if rhGH increases final adult height.
- Further research is needed to fully understand long-term outcomes and safety profiles.
Background:
Growth retardation is a common complication of chronic kidney disease (CKD) in children and is of concern to families. Recombinant human growth hormone (rhGH) treatment has been used to help short children with CKD attain a height more in keeping with their age group. However there are concerns about the long-term benefits of rhGH in significantly improving adult height as well as concerns about potential adverse effects (deterioration in native kidney function, increased acute rejection in kidney transplant recipients, benign intracranial hypertension).
Objectives:
To evaluate the benefits and harms of rhGH treatment in children with CKD.
Search Methods:
Randomised controlled trials (RCTs) were identified from the Cochrane Renal Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 12, 2011), MEDLINE (from 1966), EMBASE (from 1980), article reference lists and through contact with local and international experts in the field.Date of last search: December 29, 2011
Selection Criteria:
RCTs were included if they were carried out in children aged zero to 18 years, diagnosed with CKD, who were pre-dialysis, on dialysis or post-transplant; if they compared rhGH treatment with placebo/no treatment or two doses of rhGH treatments; and if they included height outcomes.
Data Collection And Analysis:
Two authors independently assessed studies for risk of bias and extracted data from eligible studies. Data was pooled using a random effects model with calculation of mean difference (MD) for continuous outcomes with 95% confidence intervals (CI).
Main Results:
Sixteen studies (enrolling 809 children) were identified. Risk of bias assessment indicated that study quality was poor or poorly reported with only four and five studies respectively reporting adequate allocation concealment or blinding of study participants and investigators. Treatment with rhGH (28 IU/m²/wk) compared with placebo or no specific therapy resulted in a significant increase in height standard deviation score (HSDS) at one year (8 studies, 391 children: MD 0.82, 95% CI 0.56 to 1.07), and a significant increase in height velocity at six months (2 studies, 27 children: MD 2.85 cm/6 mo, 95% CI 2.22 to 3.48) and one year (7 studies, 287 children: MD 3.88 cm/y, 95% CI 3.32 to 4.44). Height velocity, though reduced, remained significantly greater than untreated children during the second year of therapy (1 study, 82 children: MD 2.30 cm/y, 95% CI 1.39 to 3.21). Compared to the 14 IU/m²/wk group, there was a 1.18 cm/y increase in height velocity in the 28 IU/m²/wk group (3 studies, 150 children: 1.18 cm/y, 95% CI 0.52 to 1.84) . The frequency of reported side effects of rhGH was generally similar to that of the control group.
Authors' Conclusions:
One year of 28 IU/m²/wk rhGH in children with CKD resulted in a 3.88 cm increase in height velocity above that of untreated patients. Studies were too short to determine if continuing treatment resulted in an increase in final adult height.
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