Bernardor Julie, Flammier Sacha, Zagozdzon Ilona, Lalayiannis Alexander D, Koster-Kamphuis Linda, Verrina Enrico, Dorresteijn Eiske, Guzzo Isabella, Haffner Dieter, Shroff Rukshana, Schmitt Claus P, Bacchetta Justine
Department of Pediatric Nephrology, Rheumatology and Dermatology, Reference Center for Rare Renal Diseases, Reference Center for Rare Diseases of Phosphate and Calcium, Femme Mère Enfant Hospital, Hospices Civils de Lyon, Lyon, France.
INSERM 1033 Research Unit, Université Claude Bernard Lyon 1, Lyon, France.
Kidney Int Rep. 2024 May 7;9(7):2096-2109. doi: 10.1016/j.ekir.2024.04.061. eCollection 2024 Jul.
Secondary hyperparathyroidism (sHPT) is particularly severe in rapidly growing infants in dialysis. Although cinacalcet is effective and licensed in dialysis in children aged >3 years, its efficacy and safety for children aged <3 years is unknown.
We identified 26 children aged <3 years who were on dialysis and treated with cinacalcet between 2009 and 2021 in 8 European pediatric centers.
Median (interquartile range) age at the start of cinacalcet was 18 (interquartile range: 11-27) months, serum parathyroid hormone (PTH) was 792 (411-1397) pg/ml, corresponding to 11.6 (5.9-19.8) times the upper limit of normal (ULN). Serum calcium was 2.56 (2.43-2.75) mmol/l, and serum phosphate 1.47 (1.16-1.71) mmol/l. Serum 25-OH vitamin D (25-OHD) was 70 (60-89) nmol/l, 3 children were vitamin D deficient (<50 nmol/l). The initial cinacalcet dose was 0.4 (0.2-0.8) mg/kg/d and the maximum dose was 1.1 (0.6-1.2) mg/kg/d. The median follow-up under cinacalcet was 1.2 (0.7-2.0) years. PTH decreased to 4.3 (2.2-7.8) times the ULN after 6 months, to 2.0 (1.0-5.3) times ULN after 12 months, and to 1.6 (0.5-3.4) times thereafter ( = 0.017/0.003/<0.0001, log-transformed PTH). Seven of the 26 infants developed 10 hypocalcemic episodes <2.10 mmol/l. Oral calcium intake was 84% (66%-117%) of recommended nutrient intake at start, 100% (64%-142%) at 3 months and declined to 78% (65%-102%) at 12 months of therapy. Three children developed clinical signs of precocious puberty.
Cinacalcet efficiently controlled severe sHPT in children aged <3 years and was associated with hypocalcemic episodes (similar to what is observed in older children) and precious puberty, thereby mandating meticulous control of calcium (considering nutrition, supplementation, and dialysate) and endocrine changes.
继发性甲状旁腺功能亢进（sHPT）在快速生长的透析婴儿中尤为严重。尽管西那卡塞对3岁以上儿童透析有效且已获许可，但对3岁以下儿童的疗效和安全性尚不清楚。
我们确定了2009年至2021年间在8个欧洲儿科中心接受透析并接受西那卡塞治疗的26名3岁以下儿童。
开始使用西那卡塞时的中位（四分位间距）年龄为18（四分位间距：11 - 27）个月，血清甲状旁腺激素（PTH）为792（411 - 1397）pg/ml，相当于正常上限（ULN）的11.6（5.9 - 19.8）倍。血清钙为2.56（2.43 - 2.75）mmol/l，血清磷为1.47（1.16 - 1.71）mmol/l。血清25 - 羟基维生素D（25 - OHD）为70（60 - 89）nmol/l，3名儿童维生素D缺乏（<50 nmol/l）。西那卡塞初始剂量为0.4（0.2 - 0.8）mg/kg/d，最大剂量为1.1（0.6 - 1.2）mg/kg/d。西那卡塞治疗的中位随访时间为1.2（0.7 - 2.0）年。6个月后PTH降至ULN的4.3（2.2 - 7.8）倍，12个月后降至ULN的2.0（1.0 - 5.3）倍，此后降至1.6（0.5 - 3.4）倍（对数转换后的PTH，P = 0.017/0.003/<0.0001）。26名婴儿中有7名发生了10次血钙低于2.10 mmol/l的低钙血症发作。开始时口服钙摄入量为推荐营养素摄入量的84%（66% - 117%），3个月时为100%（64% - 142%），治疗12个月时降至78%（65% - 102%）。3名儿童出现性早熟的临床体征。
西那卡塞有效控制了3岁以下儿童的严重sHPT，并与低钙血症发作（与大龄儿童观察到的情况相似）和性早熟有关，因此需要严格控制钙（考虑营养、补充剂和透析液）和内分泌变化。
