Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710, USA; email:
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Annu Rev Physiol. 2020 Feb 10;82:365-390. doi: 10.1146/annurev-physiol-021119-034650. Epub 2019 Nov 19.
Chronic kidney disease (CKD) is a global health epidemic that accelerates cardiovascular disease, increases risk of infection, and causes anemia and bone disease, among other complications that collectively increase risk of premature death. Alterations in calcium and phosphate homeostasis have long been considered nontraditional risk factors for many of the most morbid outcomes of CKD. The discovery of fibroblast growth factor 23 (FGF23), which revolutionized the diagnosis and treatment of rare hereditary disorders of FGF23 excess that cause hypophosphatemic rickets, has also driven major paradigm shifts in our understanding of the pathophysiology and downstream end-organ complications of disordered mineral metabolism in CKD. As research of FGF23 in CKD has rapidly advanced, major new questions about its regulation and effects continuously emerge. These are promoting exciting innovations in laboratory, patient-oriented, and epidemiological research and stimulating clinical trials of new therapies and repurposing of existing ones to target FGF23.
慢性肾脏病(CKD)是一种全球性的健康流行病,它会加速心血管疾病的发生,增加感染风险,并导致贫血和骨骼疾病等并发症,这些并发症共同增加了过早死亡的风险。钙和磷酸盐稳态的改变一直被认为是 CKD 大多数严重后果的非传统危险因素。成纤维细胞生长因子 23(FGF23)的发现彻底改变了 FGF23 过量引起低磷性佝偻病等罕见遗传性疾病的诊断和治疗,也使我们对 CKD 中矿物质代谢紊乱的病理生理学和下游终末器官并发症的理解发生了重大转变。随着对 CKD 中 FGF23 的研究迅速推进,关于其调节和作用的重大新问题不断出现。这些问题推动了实验室、以患者为中心和流行病学研究的创新,并刺激了新疗法的临床试验和现有疗法的重新定位,以针对 FGF23。