Bernardor Julie, Flammier Sacha, Salles Jean-Pierre, Amouroux Cyril, Castanet Mireille, Lienhardt Anne, Martinerie Laetitia, Damgov Ivan, Linglart Agnès, Bacchetta Justine
Centre de Référence des Maladies Rares du Calcium et du Phosphore, Centre de Référence des Maladies Rénales Rares, Filières de Santé Maladies Rares OSCAR, ORKID et ERKNet, Service de Néphrologie Rhumatologie et Dermatologie Pédiatriques, Hôpital Femme Mère Enfant, Bron, France.
INSERM UMR S1033 Research Unit, Lyon, France.
Front Pediatr. 2022 Aug 24;10:926986. doi: 10.3389/fped.2022.926986. eCollection 2022.
Cinacalcet is a calcimimetic approved in adults with primary hyperparathyroidism (PHPT). Few cases reports described its use in pediatric HPT, with challenges related to the risk of hypocalcemia, increased QT interval and drug interactions. In this study, we report the French experience in this setting.
We retrospectively analyzed data from 18 pediatric patients from 7 tertiary centers who received cinacalcet for PHPT. The results are presented as median (interquartile range).
At a median age of 10.8 (2.0-14.4) years, 18 patients received cinacalcet for primary HPT ( = 13 inactive mutation, = 1 mutation, = 1 multiple endocrine neoplasia type 1, N=3 unknown etiology). Cinacalcet was introduced at an estimated glomerular filtration rate (eGFR) of 120 (111-130) mL/min/1.73 m, plasma calcium of 3.04 (2.96-3.14) mmol/L, plasma phosphate of 1.1 (1.0-1.3) mmol/L, age-standardized (z score) phosphate of -3.0 (-3.5;-1.9), total ALP of 212 (164-245) UI/L, 25-OHD of 37 (20-46) ng/L, age-standardized (z score) ALP of -2.4 (-3.7;-1.4), PTH of 75 (59-123) ng/L corresponding to 1.2 (1.0-2.3)-time the upper limit for normal (ULN). The starting daily dose of cinacalcet was 0.7 (0.6-1.0) mg/kg, with a maximum dose of 1.0 (0.9-1.4) mg/kg per day. With a follow-up of 2.2 (1.3-4.3) years on cinacalcet therapy, PTH and calcium significantly decreased to 37 (34-54) ng/L, corresponding to 0.8 (0.5-0.8) ULN ( = 0.01), and 2.66 (2.55-2.90) mmol/L ( = 0.002), respectively. In contrast, eGFR, 25-OHD, ALP and phosphate and urinary calcium levels remained stable. Nephrocalcinosis was not reported but one patient displayed nephrolithiasis. Cinacalcet was progressively withdrawn in three patients; no side effects were reported.
Cinacalcet in pediatric HPT can control hypercalcemia and PTH without significant side effects.
西那卡塞是一种已被批准用于治疗成人原发性甲状旁腺功能亢进症（PHPT）的拟钙剂。很少有病例报告描述其在儿童甲状旁腺功能亢进症（HPT）中的应用，且存在与低钙血症风险、QT间期延长和药物相互作用相关的挑战。在本研究中，我们报告了法国在这方面的经验。
我们回顾性分析了来自7个三级中心的18例接受西那卡塞治疗PHPT的儿科患者的数据。结果以中位数（四分位间距）表示。
患者的中位年龄为10.8（2.0 - 14.4）岁，18例患者接受西那卡塞治疗原发性HPT（13例为无活性突变，1例为 突变，1例为1型多发性内分泌腺瘤，3例病因不明）。开始使用西那卡塞时的估计肾小球滤过率（eGFR）为120（111 - 130）mL/min/1.73 m²，血浆钙为3.04（2.96 - 3.14）mmol/L，血浆磷为1.1（1.0 - 1.3）mmol/L，年龄标准化（z评分）磷为 - 3.0（ - 3.5； - 1.9），总碱性磷酸酶（ALP）为212（164 - 245）UI/L，25 - 羟维生素D（25 - OHD）为37（20 - 46）ng/L，年龄标准化（z评分）ALP为 - 2.4（ - 3.7； - 1.4），甲状旁腺激素（PTH）为75（59 - 123）ng/L，相当于正常上限（ULN）的1.2（1.0 - 2.3）倍。西那卡塞的起始日剂量为0.7（0.6 - 1.0）mg/kg，最大剂量为1.0（0.9 - 1.4）mg/kg/天。接受西那卡塞治疗2.2（1.3 - 4.3）年的随访后，PTH和血钙显著下降至37（34 - 54）ng/L，相当于0.8（0.5 - 0.8）ULN（P = 0.01），以及2.66（2.55 - 2.90）mmol/L（P = 0.002）。相比之下，eGFR、25 - OHD、ALP、磷和尿钙水平保持稳定。未报告肾钙质沉着症，但有1例患者出现肾结石。3例患者逐渐停用西那卡塞；未报告副作用。
西那卡塞用于儿童HPT可控制高钙血症和PTH，且无明显副作用。
