Nitta Kosaku, Nagano Nobuo, Tsuchiya Ken
Kidney Center, Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Nephron Clin Pract. 2014;128(1-2):1-10. doi: 10.1159/000365787. Epub 2014 Nov 8.
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone that regulates phosphate and 1,25-hydroxyvitamin D [1,25(OH)2D] metabolism. FGF23 binds to FGF receptor 1 with its coreceptor Klotho and maintains serum phosphate levels within the normal range by increasing renal phosphate excretion. In addition, FGF23 reduces the synthesis and accelerates the degradation of 1,25(OH)2D to reduce intestinal phosphate absorption. Moreover, FGF23 acts at the parathyroid gland to decrease parathyroid hormone synthesis and secretion. In chronic kidney disease (CKD), serum FGF23 levels rise exponentially as renal function declines long before a significant increase in serum phosphate concentration occurs. Although there is room for argument, FGF23 and Klotho are recently reported contributors to vascular calcification. Finally, prospective observational studies have shown that serum FGF23 concentrations predict mortality not only among dialysis patients but among predialysis CKD patients. In addition to being a coreceptor for FGF23, Klotho circulates as an endocrine substance and exerts a multitude of effects. This review describes recent advances in research on the FGF23-Klotho axis in CKD. © 2014 S. Karger AG, Basel.
成纤维细胞生长因子23（FGF23）是一种骨源性激素，可调节磷酸盐和1,25 - 二羟维生素D [1,25(OH)2D] 的代谢。FGF23与其共受体α-klotho结合至FGF受体1，并通过增加肾脏磷酸盐排泄将血清磷酸盐水平维持在正常范围内。此外，FGF23可减少1,25(OH)2D的合成并加速其降解，以减少肠道磷酸盐吸收。此外，FGF23作用于甲状旁腺，减少甲状旁腺激素的合成与分泌。在慢性肾脏病（CKD）中，早在血清磷酸盐浓度显著升高之前，血清FGF23水平就会随着肾功能下降呈指数级上升。尽管存在争议，但最近有报道称FGF23和α-klotho是血管钙化的促成因素。最后，前瞻性观察研究表明，血清FGF23浓度不仅可预测透析患者的死亡率，还可预测未透析CKD患者的死亡率。除了作为FGF23的共受体外，α-klotho还作为一种内分泌物质循环，并发挥多种作用。本文综述了CKD中FGF23-α-klotho轴的最新研究进展。© 2014 S. Karger AG，巴塞尔。
