■X连锁低磷酸盐血症病(XLH)是一种罕见的遗传性疾病,其特征是循环成纤维细胞生长因子23(FGF-23)不适当地升高和随后的尿磷酸盐消耗。XLH的主要临床表现包括身材矮小,下肢鞠躬,牙脓肿,和病。历史治疗包括磷酸盐和维生素D补充,但是最近,burosumab的靶向治疗已获得广泛接受。Burosumab是FGF-23阻断抗体。传统的治疗选择与肾钙化病(NC)的发展有关,XLH患者的报告发生率在33%至80%之间。以前的研究已经指出,磷酸盐补充剂量与NC的存在相关,尽管这一发现在各研究中并不一致。目前尚不清楚现在使用burosumab治疗的患者是否会发生肾钙化病。我们的目的是在我们的XLH儿童队列中确定XLH相关的肾钙质沉着危险因素,并提供burosumab时代的最新分析。
■我们确定了13名XLH儿童,他们在2015年至2023年之间在我们的机构接受了XLH的常规医疗护理。所有患者最初均接受常规治疗,并在2018年获得美国食品和药物管理局(FDA)批准后或在2018年之后的6个月大时过渡到burosumab。所有患者均接受常规监测,包括实验室检查和肾脏超声检查。定期调整磷酸盐和骨化三醇的剂量,以最大程度地减少血清和尿液实验室异常。Burosumab根据其FDA包装说明书的指示进行给药。分析NC组和无NC组之间的药物剂量和实验室值。
■在研究时间表内,发现3名患者有NC的证据。两名儿童在接受常规治疗时患上NC,一名儿童在服用burosumab时患上NC。没有变量,包括积极的XLH家族史,诊断为XLH的平均年龄,常规治疗的持续时间或剂量,Burosumab开始时的平均年龄,和所有测量的实验室值,有和没有NC的组之间存在显着差异。女性性别是诊断XLH相关NC的唯一重要危险因素。
■XLH相关的NC仍然是一个临床问题,即使是现代治疗,尽管传统的危险因素(磷酸盐补充剂的剂量和尿磷酸盐的排泄程度)可能并不总是与肾钙质沉着的发作相关。XLH患者接受burosumab,这是为了消除NC的风险因素,仍然可以发展NC。重要的是继续筛查接受burosumab治疗的患者是否患有肾钙质沉着症。此外,需要更多的研究来更好地了解导致XLH相关NC的危险因素,并确定从未接受过常规治疗的XLH患儿是否会发生NC.
UNASSIGNED: X-linked hypophosphatemic rickets (XLH) is a rare genetic disease characterized by inappropriately elevated circulating fibroblast growth factor 23 (FGF-23) and subsequent urinary phosphate wasting. The primary clinical manifestations of XLH include short stature, lower extremity bowing, dental abscesses, and rickets. Historical treatment includes phosphate and vitamin D supplementation, but recently, targeted therapy with burosumab has gained widespread acceptance.
Burosumab is an FGF-23 blocking antibody. Conventional therapy options have been associated with the development of nephrocalcinosis (NC), with reported rates varying between 33% and 80% in XLH patients. Previous studies have noted that the phosphate supplementation dose correlates with the presence of NC, although this finding is not consistent across studies. It remains unclear whether nephrocalcinosis occurs in patients now treated with
burosumab. Our aim was to identify XLH-associated nephrocalcinosis risk factors in our cohort of children with XLH and provide an updated analysis in the era of burosumab.
UNASSIGNED: We identified 13 children with XLH who received routine medical care for XLH at our institution between 2015 and 2023. All were initially treated with conventional therapy and were transitioned to burosumab either upon its US Food and Drug Administration (FDA) approval in 2018 or at 6 months of age if this occurred after 2018. All patients were routinely monitored and this included laboratory tests and renal ultrasonography. Phosphate and calcitriol dosages were regularly adjusted to minimize serum and urinary laboratory abnormalities.
Burosumab was administered according to its FDA package insert directions. Medication doses and laboratory values were analyzed between the group with NC and the group without NC.
UNASSIGNED: Three patients were noted to have evidence of NC within the study timeline. Two children developed NC while receiving conventional therapy and one while prescribed
burosumab. None of the variables, including a positive family history of XLH, average age at diagnosis of XLH, duration or dosage of treatment with conventional therapy, average age at the initiation of burosumab, and all measured laboratory values, were significantly different between the groups with and without NC. Female sex was the only identified significant risk factor for a diagnosis of XLH-associated NC.
UNASSIGNED: XLH-associated NC remains a clinical concern even with modern treatment, although the traditional risk factors (dose of phosphate supplements and degree of urinary phosphate excretion) may not always correlate with the onset of nephrocalcinosis. XLH patients receiving burosumab, which has been hypothesized to eliminate the risk factors for NC, can still develop NC. It is important to continue screening patients treated with
burosumab for nephrocalcinosis. In addition, more research is needed to better understand the risk factors that cause XLH-associated NC and determine whether children with XLH never exposed to conventional therapy will develop NC.