Division of Nephrology, Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA.
Curr Opin Nephrol Hypertens. 2020 Sep;29(5):531-536. doi: 10.1097/MNH.0000000000000631.
Perturbations in phosphate and vitamin D homeostasis impacts skeletal health in children and adults. Study of inherited and acquired hypophosphatemic syndromes led to the discovery of fibroblast growth factor 23 (FGF23) as a potent regulator of phosphate and vitamin D metabolism, and advanced our understanding of the pathophysiology of mineral and bone disorder in chronic kidney disease (CKD-MBD). Here, we review a recently approved therapy for patients with X-linked hypophosphatemia (XLH) using a novel anti-FGF23 antibody, burosumab, and discuss the implications of such targeted therapy in CKD.
In children and adults with XLH, burosumab treatment significantly increased renal tubular phosphate reabsorption and normalized serum phosphorus concentrations. Prolonged treatment with burosumab showed a favorable safety profile, improved healing of rickets in children, and fractures and pseudofractures in adults. FGF23 excess in CKD is independently associated with left ventricular hypertrophy and cardiovascular mortality. Research strategies to lower FGF23 in animal models of CKD are rapidly advancing and a question that remains to be answered is whether FGF23 blockade will offer a new targeted intervention for disordered mineral metabolism in CKD.
Findings from recently concluded clinical trials in adults and children with XLH provide evidence for improved skeletal health with burosumab therapy with normalization of phosphate and vitamin D metabolism. Targeted anti-FGF23 antibody treatment of XLH has emerged as a novel therapeutic strategy to treat an inherited disorder of FGF23 excess.
磷酸盐和维生素 D 稳态的紊乱会影响儿童和成人的骨骼健康。对遗传性和获得性低磷血症综合征的研究导致了成纤维细胞生长因子 23（FGF23）的发现，它是一种有效的磷酸盐和维生素 D 代谢调节剂，并促进了我们对慢性肾脏病（CKD）中矿物质和骨代谢紊乱的病理生理学的理解。在这里，我们回顾了一种最近批准的用于治疗 X 连锁低磷血症（XLH）的新型抗 FGF23 抗体布罗索尤单抗的治疗方法，并讨论了这种靶向治疗在 CKD 中的意义。
在 XLH 儿童和成人中，布罗索尤单抗治疗显著增加了肾小管磷酸盐重吸收并使血清磷浓度正常化。长期布罗索尤单抗治疗显示出良好的安全性特征，改善了儿童佝偻病的愈合，并减少了成人的骨折和假性骨折。CKD 中的 FGF23 过多与左心室肥厚和心血管死亡率独立相关。在 CKD 动物模型中降低 FGF23 的研究策略正在迅速推进，一个悬而未决的问题是 FGF23 阻断是否会为 CKD 中的矿物质代谢紊乱提供新的靶向干预。
最近在 XLH 成人和儿童中进行的临床试验结果提供了证据，表明布罗索尤单抗治疗可改善骨骼健康，使磷酸盐和维生素 D 代谢正常化。针对 FGF23 过量的靶向抗 FGF23 抗体治疗已成为治疗 FGF23 过度遗传疾病的一种新的治疗策略。
