USE OF RECOMBINANT HUMAN GROWTH-HORMONE IN CHILDREN WITH CHRONIC RENAL-INSUFFICIENCY - AN UPDATE

Growth retardation is common in children with chronic renal insufficiency (CRI). Now that dialysis and renal transplantation (TX) have become life sustaining, permanent stunted growth and adult short stature often occurs. Thus, efforts to enhance growth using recombinant human growth hormone (rhGH) have been undertaken in three groups of patients: chronic renal failure (CRF) prior to dialysis, end-stage renal disease (ESRD) on some form of dialysis; and following TX (post-TX) in whom growth retardation persists. Our initial study was in CRF. Eleven males, ages 2.5-16.3 years, with height standard deviation scores (SDS) of >2.0 below the mean, have been treated with rhGH for 18-48 months. rhGH was started in a dose of 0.125 mg/kg three times a week in the first 8 patients and subsequently changed to daily dosing (0.053 mg/kg/day) within the first 24 months. To date, overall, growth velocity (GV) increased from 5.4 +/- 2.2 to 8.9 +/- 1.6, 7.5 +/- 1.8, 7.5 +/- 1.6 and 6.9 +/- 0.9 cm/year in those completing 12 (n = 11), 24 (n = 9), 36 (n = 7), and 48 (n = 3) months. The mean height SDS increased from >3.0 to < 1. 5 below the mean with 1 patient reaching the 50th centile. Dialysis was initiated in 2 patients, a frequency not different from that expected over time in children with this degree of CRF. In the others, calculated creatinine clearance did not change, and no significant adverse effects were noted as a consequence of the rhGH treatment. Thus, rhGH increases GV and facilitates catch-up growth in CRF. Following the initiation of our study in CRF, a US national multicenter double-blind placebo-controlled study of rhGH in CRF was begun. The reported 2-year results of that study support our initial findings of a significant increase in GV and improvement in height SDS score over baseline in the rhGH-treated group as compared with placebo over the 2 years of the study. Our experience with rhGH in ESRD patients on continuous cycling peritoneal dialysis (CCPD) is less extensive. Of 5 children with marked growth failure (SDS -4.68) on CCPD for longer than 1 year, 2 experienced an increase in GV, and 1 maintained growth to achieve a gain in height SDS score. These data suggest that, while some children may be helped by rhGH even when ESRD occurs, treatment appears to be more effective when begun at an earlier degree of CRI. Our experience in post-TX patients includes 13 children with short stature or slow growth in whom rhGH was initiated 14-92 months post-TX and given, to date, for 12 (n = 13), 24 (n = 9) and 36 (n = 2) months. GV increased in the first 2 years of treatment as did the height SDS of some patients. However, the older age and pubertal status of many of these patients makes growth analysis more difficult. These data and those reported by others worldwide support the efficacy of rhGH therapy in increasing growth velocity and improving height SDS in patients with CRI. Final height outcome and long-term safety data are not yet known.