HDCN Article Review/Hyperlink

Fine RN, Kohaut E, Brown D, Kuntze J, Attie KM

Long-term treatment of growth-retarded children with chronic renal insufficiency with recombinant human growth hormone

Kidney Int (Mar) 49:781-785 1996

Growth delay is a frequent complication of childhood renal disease despite treatment of acidosis and the use of calcitriol: lifelong short stature leads to psychosocial maladjustment and limits eventual rehabilitation in a population which has otherwise benefited much from advances in dialysis and transplantation. Uncontrolled and placebo-controlled studies have demonstrated that recombinant human growth hormone (rhGH) accelerates linear growth in children with CRI with acceptable safety, with previous published experience at 2 years of follow-up.

In this paper Fine et al provide 5 years of data on 20 patients with CRI (calculated creatinine clearance 11.1 - 83.9 ml/min/1.73 m2, mean 32.2) and short stature (mean standardized height -2.6 +/- 0.8, range -1.0 to - 4.3) treated with rhGH at 0.05 mg/kg/day subcutaneously, all of whom had significant improvement in growth rate. Therapy was stopped in eight patients who reached the 50th centile for mid-parental height, but was resumed in four because of significant reduction in standardized height.

As has been reported elsewhere, growth rate was greatest in the first year of therapy (mean 12.2 +/- 2.8 cm/year) and declined in subsequent years. Patients whose therapy was paused or discontinued were included in the calculated growth rate, explaining some of the decline in response. Bone age did not advance beyond height age (i.e., skeletal maturation rate was appropriate to growth rate), thus height potential was maintained. Renal function (as calculated creatinine clearance) declined gradually with a significant difference noted only at 5 years. However serum glucose and insulin levels increased significantly with rhGH therapy. Mean serum calcium fell and alkaline phosphatase rose with therapy. Parathyroid hormone and osteocalcin values unfortunately were not reported. One patient developed avascular necrosis of the femoral head during year 4 of rhGH treatment (a previously reported complication); no other adverse events were reported.

Comment: Recombinant growth hormone has become an established part of the therapy of prepubertal children with CRI and this paper provides encouraging data regarding long-term efficacy and safety. While mean standardized height improved after the first year of treatment and that improvement was sustained for the ensuing four years, it is not clear whether all patients benefited. Data are presented only as group means, so one cannot compare individual responses or characteristics of those patients with excellent or poor responses.

Questions remain regarding the effects of rhGH on the metabolic bone disease of CRI and whether bone disease affects the growth response. Development of insulin resistance was clearly demonstrated in this population, although the mechanisms involved and the longterm consequences are still unknown. (Susan R. Mendley, M.D., Northwestern University)