Improvement in growth after 1 year of growth hormone therapy in well-nourished infants with growth retardation secondary to chronic renal failure: results of a multicenter, controlled, randomized, open clinical trial

Abstract

Background and objectives: Our aim was to evaluate the growth-promoting effect of growth hormone (GH) treatment in infants with chronic renal failure (CRF) and persistent growth retardation despite adequate nutritional and metabolic management.

Design, setting, participants, & measurements: The study design included randomized, parallel groups in an open, multicenter trial comparing GH (0.33 mg/kg per wk) with nontreatment with GH during 12 months. Sixteen infants who had growth retardation, were aged 12+/-3 months, had CRF (GFR<or=60 ml/min per 1.73 m2), and had adequate nutritional intake and good metabolic control were recruited from eight pediatric nephrology departments from Spain and Portugal. Main outcome measures were body length, body weight, bone age, biochemical and hormonal analyses, renal function, bone mass, and adverse effects.

Results: Length gain in infants who were treated with GH was statistically greater (P<0.05) than that of nontreated children (14.5 versus 9.5 cm/yr; SD score 1.43 versus -0.11). The GH-induced stimulation of growth was associated with no undesirable effects on bone maturation, renal failure progression, or metabolic control. In addition, GH treatment improved forearm bone mass and increased serum concentrations of total and free IGF-I and IGF-binding protein 3 (IGFBP-3), whereas IGF-II, IGFBP-1, IGFBP-2, GH-binding protein, ghrelin, and leptin were not modified.

Conclusions: Infants with CRF and growth retardation despite good metabolic and nutritional control benefit from GH treatment without adverse effects during 12 months of therapy.

Trial registration: ClinicalTrials.gov NCT00184769.

Figure 1.

(A and B) Evolution of body length (A) and body weight (B) during the 1-year study period in the two groups of infants with CRF. ■, Untreated group; □, GH-treated group. Data are means ± SEM of SDS for length. P values of intergroup comparisons at that particular time point. *Intragroup significant change compared with the corresponding baseline (Bonferroni adjusted P < 0.05).

Figure 2.

Dual-energy x-ray absorptiometry results performed on total radius in both groups of patients. (A) Bone area (cm²). (B) Bone mineral content (g). (C) Bone mineral density (g/cm²). Data are means ± SEM. P values of intragroup comparisons at that particular time point. Solid and dashed lines and intragroup P values symbolize the untreated and the GH-treated groups, respectively.

Figure 3.

(A and B) Evolution of IGF-I (A) and IGFBP-3 (B) during the 1-year study period in the two groups of infants with CRF. ■, Untreated group; □, GH-treated group. Data are means ± SEM of SDS for reference values. P values of intergroup comparisons at that particular time point. *Intragroup significant change compared with the corresponding baseline (Bonferroni adjusted P < 0.05).

Figure 4.

(A and B) Basal and final bone age (A) and bone age–chronological age ratio (B) in both groups of patients. ■, Untreated group; □, GH-treated group. Data are means ± SEM. ‡Intragroup significant change compared with the corresponding baseline (Bonferroni adjusted P < 0.001).