Introduction
Growth assessment
Growth features post-transplantation
Magnitude of growth impairment post-transplantation
Study | Tx period | Population (n) | rhGH post-Tx (n) | Age at Tx (years) | Follow-up (years) | Height SDSa
| Growth determinants | ||
---|---|---|---|---|---|---|---|---|---|
At Tx | Final Height | Normal heightb
| |||||||
Andre et al. 2003 [5] | 1975 | 19 (11 boys) | 0 | 13.2 | 10.9 | −3.1 | −2.6 | 42% | Height at ESRD; duration and cause of ESRD |
Englund et al. 2003 [6] | 1981–1994 | 24 (8 boys) | 6 | 9.5 | 7.6 | −1.7 | −1.1 | 75% | Height at Tx; bone age; graft function |
Ninik et al. 2002 [7] | 1985–1998 | 82 (53 boys) | 0 | 10.3 | > 5 | −2.1 (n = 82) | −1.3 (n = 47) | - | Height at Tx; age at Tx; final GFR; steroid dose |
Nissel et al. 2004 [8] | 1983–2002 | 37 (18 boys) | 0 | 10.2 (girls) | 8.5 | −2.9 (girls) | −1.9 (girls) | 68% | Height at Tx; graft function |
12.5 (boys) | −1.7 (boys) | −1.0 (boys) | |||||||
Offner et al. 1999 [9] | 1970–1993 | 100 (47 boys) | 7 | 13.6 | 13.1 | −2.2 | −2.4c
| 47%c
| - |
Rodriguez-Soriano et al. 2000 [10] | 1986–1999 | 32 (17 boys) | 3 | 12.1 | 7.2 (median) | −1.6 (girls) | −1.2 (girls) | 69% | Height at Tx and at start of dialysis; duration of dialysis |
−1.4 (boys) | −1.6 (boys) |
Impact of growth failure post-transplantation
Factors influencing growth post-transplantation
Pre-transplantation growth
Role of age at transplantation
Effect of graft function
Role of steroid therapy
Other factors
Pathophysiology of growth impairment post-transplantation
Disturbances in the growth hormone/insulin-like growth factor axis
Metabolic acidosis
Secondary hyperparathyroidism
Nutrition
Management of growth post-transplantation
Conservative strategies
Causes of growth impairment | Methods |
---|---|
Reduced GFR | Prevention and management of chronic allograft nephropathy |
Treatment of acute rejection episodes | |
Drug compliance | |
Steroid therapy | Daily low or alternate day steroid therapy |
Steroid avoidance/withdrawal under evaluation | |
Bone disease | Target PTH within normal range in CKD stage 2–3 and < 2× upper limit in CKD stage 4 |
Target plasma phosphate within age-appropriate normal range | |
Metabolic acidosis | Target plasma bicarbonate > 22 mmol/L |
Malnutrition | Adequate nutritional intake |
Comorbidities | Assessment and control of comorbidities which may impair growth (chronic inflammation, liver, lung or heart diseases) |
Growth hormone therapy
Efficacy and safety
Study | Design | Population | Growth velocity (cm/year) | Safety | ||
---|---|---|---|---|---|---|
rhGH group | Controls | Rejections | GFR | |||
Hokken-Koleaga et al. 1996 [67] | 6-months crossover | n = 11 | No episode | No change | ||
5 prepubertal | 3.9 (6 months) | 1.0 | ||||
6 pubertal | 5.3 | 1.5 | ||||
Maxwell et al. 1998 [68] | 1-year randomized | n = 22 | 8/13 in rhGH group vs. 5/9 in controlsa
| No change | ||
15 prepubertal | 8.1 | 3.7 | ||||
7 pubertal | 10.1 | 3.9 | ||||
Guest et al. 1998 [69] | 1-year randomized | n = 90 | 7.7 | 4.6 | 9/44 in rhGH group vs. 4/46 in controlsa
| No change |
55 prepubertal | ||||||
35 pubertal | ||||||
Fine et al. 2002 [70] | 1-year randomized | n = 63 | 9.0 | 4.2 | None in rhGH group vs. 3 in controls | No change in SCrb
|
40 prepubertal | ||||||
23 pubertal |
Current recommendations
Recombinant human growth hormone therapy | Factors to take into consideration |
---|---|
Target population for rhGH therapy | Prepubertal children |
Pubertal children? | |
−2 SDS for height | |
Poor growth velocity? | |
Growth potential documented by open epiphyses | |
Correction of other factors contributing to growth failure | |
Contra-indication | Active malignancy |
Baseline evaluation | Pubertal stage |
Anthropometric assessment | |
Target height | |
Hip X-ray and bone age | |
Fundoscopic examination | |
Serum phosphate, calcium and PTH | |
Optimal dose of rhGH | 0.05 mg/kg per day (4 IU/m2 per day) |
Mode of administration | Daily subcutaneous injection |
Follow-up evaluation | Height, weight, growth velocity every 3 months |
Close monitoring of graft function in children with a history of acute rejection | |
Serum calcium, phosphate and PTH every 3 months | |
Bone age every year according to growth profile | |
rhGH discontinuation | Achieved height endpoint |
Closed epiphyses | |
Slipped femoral epiphyses | |
Severe hyperparathyroidism | |
Active malignancy | |
Documented benign intracranial hypertension | |
Non compliance |