Effect of burosumab conversion on calciuria and nephrocalcinosis in children with XLH: A real-world cohort study

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports Pub Date : 2025-09-06 DOI:10.1016/j.bonr.2025.101877

Guido Filler , Harry Chandrakumaran , Funmbi Babalola , Dougenie Emile , Shih-Han Susan Huang , Robert Stein

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Abstract

Background

Burosumab, a monoclonal antibody to fibroblast growth factor 23 (FGF23), is effective for X-linked hypophosphatemic rickets (XLH). Renal effects, particularly calciuria and nephrocalcinosis, remain incompletely characterized.

Methods

In this retrospective cohort, 13 children with genetically confirmed XLH (7 females, 6 males; 0.6–16.3 years) were evaluated after conversion from conventional therapy to burosumab. Longitudinal changes in serum phosphate, TmP/GFR, TRP, 1,25(OH)₂D, intact parathyroid hormone (PTH), and urinary calcium/creatinine (Ca:Cr) were assessed. Hypercalciuria was defined using age-specific SI thresholds; Ca:Cr was also expressed as ×ULN (Ca:Cr divided by the age-specific upper limit).

Results

Burosumab improved serum phosphate (p < 0.001), TmP/GFR (p < 0.001), and TRP (p = 0.007). Despite normalized phosphate handling, two patients developed de novo nephrocalcinosis. No child was hypercalciuric at washout or Day 14; two had ≥1 episode later. A repeated-measures analysis of log10(×ULN) showed no overall time effect from washout to Day 56 (F(4,29) = 1.66, p = 0.185). A larger decline in PTH correlated with higher Ca:Cr (p < 0.05), whereas 1,25(OH)₂D did not.

Conclusion

Burosumab improves phosphate homeostasis in children with XLH, but a minority may develop hypercalciuria and nephrocalcinosis, potentially linked to PTH suppression. Vigilant biochemical and ultrasound monitoring—particularly early after conversion—and consideration of prophylaxis in high-risk cases are advisable.

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布罗单抗转换对XLH儿童钙尿症和肾钙质沉着症的影响：一项真实世界队列研究

burosumab是一种针对成纤维细胞生长因子23 （FGF23）的单克隆抗体，对x连锁低磷血症佝偻病（XLH）有效。肾脏的影响，特别是钙尿症和肾钙质沉着症，仍然不完全明确。方法在本回顾性队列研究中，对13例遗传确诊的XLH患儿（7名女性，6名男性，0.6-16.3岁）从常规治疗转为布罗单抗后进行评估。评估血清磷酸盐、TmP/GFR、TRP、1,25（OH）₂D、完整甲状旁腺激素（PTH）和尿钙/肌酐（Ca:Cr）的纵向变化。使用年龄特异性SI阈值定义高钙尿症；Ca:Cr也表示为×ULN （Ca:Cr除以年龄上限）。结果burosumab改善了血清磷酸盐（p < 0.001）、TmP/GFR （p < 0.001）和TRP （p = 0.007）。尽管正常的磷酸盐处理，两名患者发展为新肾钙质沉着症。在洗脱期或第14天，没有儿童出现高钙血症；其中2例以后有≥1次发作。log10（×ULN）的重复测量分析显示，从洗脱期到第56天没有总体时间效应（F(4,29) = 1.66, p = 0.185）。较大的PTH下降与较高的Ca:Cr相关（p < 0.05），而1,25（OH）₂D则无关。结论：burosumab可改善XLH患儿的磷酸盐稳态，但少数患者可能出现高钙尿症和肾钙质沉着症，这可能与PTH抑制有关。警惕生化和超声监测-特别是在转化后早期-并考虑预防高危病例是可取的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bone Reports Medicine-Orthopedics and Sports Medicine

CiteScore

4.30

自引率

4.00%

发文量

444

审稿时长

57 days

期刊介绍： Bone Reports is an interdisciplinary forum for the rapid publication of Original Research Articles and Case Reports across basic, translational and clinical aspects of bone and mineral metabolism. The journal publishes papers that are scientifically sound, with the peer review process focused principally on verifying sound methodologies, and correct data analysis and interpretation. We welcome studies either replicating or failing to replicate a previous study, and null findings. We fulfil a critical and current need to enhance research by publishing reproducibility studies and null findings.