Guest G, Bérard E, Crosnier H, Chevallier T, Rappaport R, Broyer M
Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France.
Pediatr Nephrol. 1998 Aug;12(6):437-46. doi: 10.1007/s004670050483.
From 1991 to 1993, 90 children having received a kidney graft with a post-transplantation period of at least 12 months were included in a prospective study carried out in 18 French pediatric centers. After informed consent and randomization, children received recombinant human growth hormone (rhGH) (Genotonorm, Pharmacia peptide hormones) 30 U/m2 per week, either immediately on enrollment, for the treated group, or after 1 year of follow-up for the group serving as a control. After 1 year both groups were treated and we analyzed data during the subsequent years. Eighty-five children completed the 1-year study. Growth velocity was significantly increased by rhGH: 7.7 cm with a gain of +0.3 standard deviation score in the treated group versus 4.6 cm in the control group (P<0.0001) during the 1st year. Four factors predicted response to therapy: growth velocity prior to GH therapy, glomerular filtration rate (GFR) at the start, mode of corticosteroid administration, and degree of insulin resistance. After 1 year we observed a moderate, significant decrease in GFR in both groups. Biopsy-proven acute rejection episodes were not significantly more frequent during the 1st year in the group of patients who received rhGH: 9 in 44 versus 4 in 46 patients. The patients who rejected did not differ in terms of age, renal function at the start, and type of immunosuppression, but history of rejection before GH treatment was discriminatory: 6 of 17 children with two or more episodes had a new rejection versus 1 of 22 who had no or only one episode (P=0.01). Glucose tolerance was not modified after 1 year of GH therapy. During the subsequent years of treatment a decrease in growth velocity was noted: 5.9 cm at 2 years, 5.5 at 3 years, and 5.2 cm at 4 years. In conclusion, GH is efficient for improving growth velocity in short transplanted children, inducing clear-cut but limited catch-up growth. The risk of rejection was shown only in patients with a prior history of more than one rejection episode.
1991年至1993年期间，18家法国儿科中心开展了一项前瞻性研究，纳入了90名接受肾移植且移植后时间至少为12个月的儿童。在获得知情同意并随机分组后，治疗组儿童在入组时立即开始接受重组人生长激素（rhGH）（Genotonorm，Pharmacia肽类激素）治疗，剂量为每周30 U/m²；对照组儿童在随访1年后开始治疗。1年后两组均接受治疗，我们对随后几年的数据进行了分析。85名儿童完成了为期1年的研究。rhGH显著提高了生长速度：治疗组第1年生长速度为7.7 cm，标准差得分增加了+0.3，而对照组为4.6 cm（P<0.0001）。有四个因素可预测对治疗的反应：GH治疗前的生长速度、开始时的肾小球滤过率（GFR）、皮质类固醇的给药方式以及胰岛素抵抗程度。1年后，我们观察到两组的GFR均有中度、显著下降。在接受rhGH治疗的患者组中，第1年经活检证实的急性排斥反应发作频率并无显著增加：44例患者中有9例发生排斥反应，而46例患者中有4例。发生排斥反应的患者在年龄、开始时的肾功能以及免疫抑制类型方面并无差异，但GH治疗前的排斥反应史具有区分性：17名有两次或更多次排斥反应发作的儿童中有6例出现了新的排斥反应，而22名无排斥反应或仅有一次排斥反应发作的儿童中有1例出现排斥反应（P=0.01）。GH治疗1年后葡萄糖耐量未发生改变。在随后的治疗年份中，生长速度有所下降：2年时为5.9 cm，3年时为5.5 cm，4年时为5.2 cm。总之，GH对改善短期移植儿童的生长速度有效，可诱导明显但有限的追赶生长。仅在有不止一次排斥反应发作既往史的患者中显示出排斥反应风险。
