Idiopathic infantile hypercalcemia in children with chronic kidney disease due to kidney hypodysplasia,Pediatric Nephrology

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Idiopathic infantile hypercalcemia in children with chronic kidney disease due to kidney hypodysplasia
Pediatric Nephrology ( IF 2.6 ) Pub Date : 2022-09-26 , DOI: 10.1007/s00467-022-05740-w
Evgenia Gurevich _{1,

2} , Yael Borovitz ₁ , Shelli Levi ₁ , Sharon Perlman _{3,

4} , Daniel Landau _{1,

4}

Affiliation

Background

Idiopathic infantile hypercalcemia (IIH) etiologies include pathogenic variants in CYP24A1, leading to increased 1,25(OH)₂ D, hypercalciuria and suppressed parathyroid hormone (PTH), and in SLC34A1 and SLC34A3, leading to the same metabolic profile via increased phosphaturia. IIH has not been previously described in CKD due to kidney hypodysplasia (KHD).

Methods

Retrospective study of children with bilateral KHD and simultaneously tested PTH and 1,25(OH)₂D, followed in a tertiary care center between 2015 and 2021.

Results

Of 295 screened patients, 139 had KHD, of them 16 (11.5%) had IIH (study group), 26 with normal PTH and any 1,25(OH)₂D were controls. There were no differences between groups’ gender, obstructive uropathy rate and baseline eGFR. Study patients were younger [median (IQR) age: 5.2 (3.2–11.3) vs. 61 (13.9–158.3) months, p < 0.001], had higher 1,25(OH)₂D (259.1 ± 91.7 vs. 156.5 ± 46.4 pmol/l, p < 0.001), total calcium (11.1 ± 0.4 vs. 10.7 ± 0.3 mg/dl, p < 0.001), and lower phosphate standard deviation score (P-SDS) [median (IQR): − 1.4 (− 1.9, − 0.4) vs. − 0.3 (− 0.8, − 0.1), p = 0.03]. During 12 months of follow-up, PTH increased among the study group (8.8 ± 2.8 to 22.7 ± 12.4 pg/ml, p < 0.001), calcium decreased (11 ± 0.5 to 10.3 ± 0.6 mg/dl, p = 0.004), 1,25(OH)₂D decreased (259.5 ± 91.7 to 188.2 ± 42.6 pmol/l, p = 0.1), P-SDS increased [median (IQR): − 1.4 (− 1.9, − 0.4) vs. − 0.3 (− 0.9, 0.4), p = 0.04], while eGFR increased. Five of 9 study group patients with available urine calcium had hypercalciuria. Five patients had nephrocalcinosis/lithiasis. Genetic analysis for pathogenic variants in CYP24A1, SLC34A1 and SLC34A3 had not been performed.

Conclusions

Transient IIH was observed in infants with KHD, in association with hypophosphatemia, resembling SLC34A1 and SLC34A3 pathogenic variants’ metabolic profile.

Graphical abstract

中文翻译：

肾发育不良所致慢性肾脏病患儿的特发性婴儿期高钙血症

背景

特发性婴儿高钙血症 (IIH) 的病因包括CYP24A1的致病变异，导致 1,25(OH) ₂ D 增加、高钙尿症和甲状旁腺激素 (PTH) 受抑制，以及SLC34A1和SLC34A3的致病变异，通过磷酸尿症增加导致相同的代谢特征。由于肾发育不良 (KHD)，IIH 之前未在 CKD 中描述过。

方法

2015 年至 2021 年间在一家三级医疗中心对双侧 KHD 儿童进行回顾性研究，同时检测 PTH 和 1,25(OH) _{2 D。}

结果

在 295 名筛查患者中，139 名患有 KHD，其中 16 名 (11.5%) 患有 IIH（研究组），26 名 PTH 正常，任何 1,25(OH) ₂ D 作为对照。各组的性别、梗阻性尿路病变发生率和基线 eGFR 之间没有差异。研究患者较年轻[中位 (IQR) 年龄：5.2 (3.2–11.3) 与 61 (13.9–158.3) 个月，p < 0.001]，具有较高的 1,25(OH) ₂ D (259.1 ± 91.7 与 156.5 ± 46.4 pmol/l，p < 0.001），总钙（11.1 ± 0.4 对比 10.7 ± 0.3 mg/dl，p < 0.001）和较低的磷酸盐标准差评分 (P-SDS) [中位数 (IQR)：- 1.4 ( − 1.9, − 0.4) 对比 − 0.3 (− 0.8, − 0.1), p = 0.03]。在 12 个月的随访期间，研究组的 PTH 增加（8.8 ± 2.8 至 22.7 ± 12.4 pg/ml，p < 0.001)，钙减少（11 ± 0.5 至 10.3 ± 0.6 mg/dl，p = 0.004），1,25(OH) ₂ D 减少（259.5 ± 91.7 至 188.2 ± 42.6 pmol/l，p = 0.1）， P-SDS 增加 [中位数 (IQR)：− 1.4 (− 1.9, − 0.4) 对比 − 0.3 (− 0.9, 0.4), p = 0.04]，而 eGFR 增加。研究组 9 名可用尿钙的患者中有 5 名患有高钙尿症。5 名患者患有肾钙质沉着症/结石症。尚未对CYP24A1、SLC34A1和SLC34A3中的致病变异进行遗传分析。