Long-term effects of growth hormone treatment on growth and puberty in patients with chronic renal insufficiency

Several prospective trials have shown that recombinant human growth hormone (GH) accelerates growth significantly during the first years of therapy, b ut the effects of long-term GH therapy with regard to longterm growth respo nse and safety have not yet been established. Forty-five Dutch prepubertal children [28 boys, 17 girls, mean (SD) age 7.8 (3.4) years] with chronic re nal insufficiency (CRI) and severe growth retardation started GH therapy be tween 1988 and 1991 within one of the randomized Dutch trials. Long-term GH therapy, in this study a maximum of 8 years, resulted in a sustained and s ignificant improvement of height standard deviation score (SDS) compared wi th baseline values (P<0.001). The mean height SDS reached the lower end (-2 SDS) of the normal growth chart after 3 years of GH therapy. During the fo llowing years the mean height SDS gradually increased, thereby approaching the mean target height SDS after 6 years of GH therapy. Three factors were significantly associated with the height SDS after 4 years of GH therapy: h eight SDS at the start (+) of therapy, age at the start of therapy (-), and the duration of dialysis treatment (-). Bone maturation did not accelerate during longterm GH therapy. Children on a conservative regimen at the star t of GH therapy had no accelerated deterioration of renal function during 6 years of GH therapy. The average daily GH dose administered over the years had no significant influence on the glomerular filtration rate after 4 yea rs. GH therapy had no adverse effects or significant effect on parathyroid hormone concentration, nor were there any radiological signs of renal osteo dystrophy. Puberty started at a median age, within the normal range, of 12. 4 years in boys and 12.0 years in girls, respectively. Long-term GH therapy leads to a sustained improvement in height SDS in children with growth ret ardation secondary to CRI, resulting in a normalization of height in accord ance with their target height SDS, without evidence of deleterious effects on renal function or bone maturation. A GH dosage of 4 IU/m(2) per day appe ars efficient and safe. Our long-term data show that final height will be w ithin the normal target height range when GH therapy is continued for many years.