Double blind trial comparing the effects of two doses of growth hormone in prepubertal patients with chronic renal insufficiency.

Growth retardation is a major problem for children with chronic renal insufficiency (CRI). Recent studies have convincingly shown that recombinant human GH accelerates growth significantly, but the optimal GH dose with regard to long term growth response and safety has not yet been established. GH therapy was given to 23 prepubertal children (18 boys and 5 girls; mean +/- SD age, 7.1 +/- 3.6 yr; range, 1.6-14.1) with CRI and severe growth retardation in a double blind, dose-response trial. Patients were randomly assigned to either 2 or 4 IU GH/m2.day for 2.5 yr. During the first 6 months, there were comparable and significant increases in height velocity SD score for chronological age with both doses (P < 0.001). However, during the ensuing 2 yr, the higher GH dose induced a significantly greater improvement in height velocity SD score for chronological age than 2 IU GH. Catch-up growth was only sustained for 2.5 yr with 4 IU. In contrast, catch-up growth ceased after 6 months with 2 IU. Neither 2 nor 4 IU GH resulted in accelerated bone maturation during 2.5 yr of therapy. There was a significant increase in plasma insulin-like growth factor-I (IGF-I) levels with either dose, but significantly more so with 4 IU. Plasma IGF-II levels only increased significantly with 4 IU. The pretreatment elevation of IGF-binding protein-1 (IGFBP-1) levels decreased by 50% during the first study year with the higher GH dose, whereas there was no decrease with 2 IU. The elevated pretreatment IGFBP-3 levels increased comparably and significantly with either GH dose. Interestingly, only 4 IU resulted in a significantly greater increase in IGF-I than in IGFBP-3 levels. Regardless of GH dose, there was an insignificant decrease in fructosamine levels, whereas lipid and parathyroid concentrations remained constant. Renal function deterioration did not accelerate. GH therapy with 4 IU/m2.day induced and maintained catch-up growth during 2.5 yr in children with CRI without evidence of adverse effects. Bone maturation did not accelerate. This suggests that this higher GH dose may be beneficial for children with severe growth retardation secondary to CRI.

RCT Entities:   Population Interventions Outcomes