Department of Paediatrics I, University Children's Hospital, Heidelberg, Germany.
Transpl Int. 2013 Sep;26(9):903-9. doi: 10.1111/tri.12148. Epub 2013 Jul 19.
Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case-control study on longitudinal growth over 2 years in steroid-free pediatric renal transplant recipients. Fourteen patients on a steroid-free maintenance immunosuppressive regimen consisting of low-dose everolimus (EVR) in conjunction with low-dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid-free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch-up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid-free pediatric patients on low-dose EVR and CsA is not different to that of a matched steroid-free control group on an immunosuppressive regimen with standard-dose CNI and MMF. Hence, low-dose EVR does not appear to negatively impact short-term growth in pediatric renal transplant recipients.
人们担心哺乳动物雷帕霉素靶蛋白抑制剂会通过抑制生长因子信号和生长板软骨细胞增殖来干扰儿科移植受者的纵向骨生长。因此，我们对 2 年内无类固醇的小儿肾移植受者进行了一项前瞻性嵌套病例对照研究，以研究纵向生长情况。14 名接受无类固醇维持性免疫抑制治疗的患者（联合使用低剂量依维莫司（EVR）和低剂量环孢素（CsA））与 14 名接受标准剂量吗替麦考酚酯（MMF）联合标准剂量钙调神经磷酸酶抑制剂（CNI）的无类固醇患者进行了比较。在研究的第一年，EVR 组身高标准差（SD）评分的平均变化为 0.31±0.71 SD 评分，而 MMF 组为 0.31±0.64 SD 评分（P=0.20）。在整个 2 年的研究期间，EVR 组身高 SD 评分的变化为 0.43±0.81 SDS，而 MMF 组为 0.75±0.85 SDS（P=0.32）。在 EVR 组中，有 5/8（65%）的青春期前患者出现追赶生长（定义为身高 SD 评分在 2 年内增加≥0.5），而 MMF 组为 6/8（75%），两组之间无显著差异（P=1.00）。接受低剂量 EVR 和 CsA 的无类固醇小儿患者在 2 年内的纵向生长与接受标准剂量 CNI 和 MMF 的无类固醇对照免疫抑制方案的患者相似。因此，低剂量 EVR 似乎不会对小儿肾移植受者的短期生长产生负面影响。
