MODULATION OF GROWTH-FACTORS BY GROWTH-HORMONE IN CHILDREN WITH CHRONIC-RENAL-FAILURE

Anthropometric measurements and circulating growth factors were studie d serially in 44 prepubertal children with growth failure and chronic renal failure (GFR = 10 to 40 ml/min/1.73 m(2)) who were randomized to receive either recombinant human growth hormone (rhGH; N = 30) or no treatment (N = 14). RhGH was given as Nutropin, 0.05 mg/kg/day, and th e studies were carried out at baseline and after 3 and 12 months. At b aseline, serum insulin-like growth factor binding protein (IGFBP)-1 an d -2 levels were, while IGFBP-3 levels were not, higher than those of children with normal renal function. In addition, height SDS at baseli ne correlated inversely with serum IGFBP-2 levels (r = -0.461, P = 0.0 016), but did nor correlate significantly with any other factor. After 12 months of study, the 30 children receiving rhGH showed: (i) greate r increase in height (9.1 +/- 2.8 vs. 5.5 +/- 1.9 cm, P < 0.0001); (ii ) increases in serum levels of IGF-I, IGF-II, free IGF-I, IGFBP-3 and acid labile subunit (ALS); (iii) a greater decrease in serum IGFBP-1 l evels; and (iv) no significant difference in serum IGFBP-2 levels, whe n compared to the 14 control patients. The change in height SDS after 12 months of rhGH (+ 0.8) in the 30 treated children correlated signif icantly and positively with serum ALS, IGFBP-3, total IGF, IGF-I, IGF- II and free IGFr-I levels measured during treatment. These observation s suggest that, in children with growth failure associated with chroni c renal failure: (i) IGFBP-2 and not IGFBP-3, is likely to be a growth inhibitor; (ii) rhGH stimulates catch-up growth in part by increasing serum levels of IGF peptides; and (iii) linear growth is influenced b y the balance between growth stimulating IGFs and growth inhibitory IG FBPs.