DOUBLE-BLIND TRIAL COMPARING THE EFFECTS OF 2 DOSES OF GROWTH-HORMONEIN 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 recom binant human GH accelerates growth significantly, but the optimal GH d ose with regard to long term growth response and safety has not yet be en established. GH therapy was given to 23 prepubertal children (18 bo ys and 5 girls; mean +/- so age, 7.1 +/- 3.6 yr; range, 1.6-14.1) with CRI and severe growth retardation in a double blind, dose-response tr ial. Patients were randomly assigned to either 2 or 4 IU GH/m(2).day f or 2.5 yr. During the first 6 months, there were comparable and signif icant 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 a fter 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 inc rease in plasma insulin-like growth factor-I (IGF-I) levels with eithe r 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 s tudy year with the higher GH dose, whereas there was no decrease with 2 IU. The elevated pretreatment IGFBP-3 levels increased comparably an d 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 fructosa mine levels, whereas lipid and parathyroid concentrations remained con stant. Renal function deterioration did not accelerate. GH therapy wit h 4 IU/m(2).day induced and maintained catch-up growth during 2.5 yr i n children with CRI without evidence of adverse effects. Bone maturati on did not accelerate. This suggests that this higher GH dose mar be b eneficial for children with severe growth retardation secondary to CRI .