Division of Pediatric Nephrology, Holtz Children's Hospital, University of Miami, P.O. Box 016960, Miami, FL, 33130, USA.
Pediatr Nephrol. 2019 Jan;34(1):129-135. doi: 10.1007/s00467-018-4055-7. Epub 2018 Sep 10.
Studies in the use of the calcimimetic, cinacalcet, in pediatric chronic kidney disease (CKD) are few and limited to older children with secondary hyperparathyroidism (sHPT), a major morbid complication contributing to poor growth, bone deformities, and cardiovascular disease. Our objectives were to determine a safe and effective dosing regimen of cinacalcet in the treatment of infants and young children with sHPT that was refractory to standard care and to examine their growth during treatment.
Ten young pediatric patients with advanced CKD were studied retrospectively during 11 courses of treatment with cinacalcet. All had severe sHPT with intact parathyroid hormone (iPTH) levels ≥ 500 pg/ml and were refractory to standard therapy with phosphate binders and active vitamin D analogs at high doses for > 30 days. The cinacalcet dose was advanced by 50% every 2-4 weeks to achieve a decline in the iPTH to a goal of 150-300 pg/ml. Linear growth was assessed at 6-month intervals by change in z-scores (△SDS) for length before and during cinacalcet therapy.
Median age at initiation of cinacalcet was 18 months (IQR 6, 36) with an average starting dose of 0.7 ± 0.2 mg/kg/day. Median effective dose required to reach iPTH goal of 150-300 pg/ml was 2.8 mg/kg/day (IQR 2.0, 3.1), and time to goal was 112 days (IQR 56, 259) with a median overall decline in iPTH of 82% from baseline by 6 months (p < 0.0001). No subject experienced a clinical adverse event, although 4 had biochemical asymptomatic hypocalcemia. Linear growth improved significantly during cinacalcet therapy (△SDS - 0.62 ± 1.2 versus + 0.91 ± 1.4; p < 0.005). By multiple regression analysis, the primary determinants of growth were concurrent treatment with growth hormone and age < 2 years (R = 89.6%; p < 0.001). A shorter treatment time required to achieve iPTH goals also was associated with improved growth (r = - 0.75; p < 0.01).
Cinacalcet may be used effectively and safely in infants and small children with refractory sHPT in advanced CKD using a cautious dosing regimen. Cinacalcet successfully brings iPTH to target level and supports growth when other treatments have been ineffective.
使用钙敏感受体激动剂西那卡塞治疗儿科慢性肾脏病（CKD）的研究很少，并且仅限于患有继发性甲状旁腺功能亢进症（sHPT）的大龄儿童，这是一种严重的并发症，可导致生长不良、骨骼畸形和心血管疾病。我们的目的是确定西那卡塞在治疗对标准治疗无反应的 sHPT 的婴儿和幼儿中的安全有效剂量方案，并检查他们在治疗期间的生长情况。
回顾性研究了 10 例患有晚期 CKD 的年轻儿科患者，他们在接受西那卡塞治疗的 11 个疗程中接受了研究。所有患者均患有严重的 sHPT，全段甲状旁腺激素（iPTH）水平≥500 pg/ml，且对高剂量磷结合剂和活性维生素 D 类似物的标准治疗无反应> 30 天。每 2-4 周将西那卡塞剂量提高 50%，以将 iPTH 降至 150-300 pg/ml 的目标范围。在接受西那卡塞治疗之前和之后，通过长度的 z 评分变化（△SDS）评估线性生长情况，以 6 个月为间隔进行评估。
西那卡塞起始年龄中位数为 18 个月（IQR 6，36），起始剂量平均为 0.7±0.2 mg/kg/天。达到 iPTH 目标范围 150-300 pg/ml 所需的中位有效剂量为 2.8 mg/kg/天（IQR 2.0，3.1），达到目标的中位时间为 112 天（IQR 56，259），中位 iPTH 基线下降 82%，在 6 个月时达到显著水平（p<0.0001）。尽管有 4 例出现了生化无症状性低钙血症，但没有患者出现临床不良事件。在西那卡塞治疗期间，线性生长显著改善（△SDS-0.62±1.2 与+0.91±1.4；p<0.005）。通过多元回归分析，生长的主要决定因素是同时接受生长激素治疗和年龄<2 岁（R=89.6%；p<0.001）。达到 iPTH 目标所需的较短治疗时间也与生长改善相关（r=-0.75；p<0.01）。
在患有晚期 CKD 且对标准治疗无反应的婴儿和幼儿中，使用谨慎的剂量方案，西那卡塞可能有效且安全地用于治疗 sHPT。当其他治疗无效时，西那卡塞可成功将 iPTH 降至目标水平并支持生长。
