Fukagawa Masafumi, Nakanishi Shohei, Fujii Hideki, Hamada Yasuhiro, Abe Takaya
Division of Nephrology and Dialysis Center, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Clin Exp Nephrol. 2006 Sep;10(3):175-9. doi: 10.1007/s10157-006-0432-9.
In chronic kidney disease (CKD), several abnormalities in bone and mineral metabolism develop in the majority of patients. The parathyroid plays a very important role in regulating bone and mineral metabolism; thus, control of parathyroid function is one of the main targets of the management of CKD-mineral and bone disorder (CKD-MBD). In the development of secondary hyperparathyroidism, it has recently been suggested that fibroblast growth factor 23 (FGF23) plays a crucial role, both as a phosphaturic factor and as a suppressor of active vitamin D (1,25D) production in the kidney. FGF23 is originally secreted to prevent hyperphosphatemia in CKD, but this occurs at the expense of low 1,25D and hyperparathyroidism ("trade-off" hypothesis revisited). Furthermore, recent data suggest that FGF23 could be another useful marker for the prognosis of hyperparathyroidism, because a high serum level may reflect the cumulative dose of vitamin D analogues previously administered. We have also demonstrated that severe hyperparathyroidism was associated with the production and secretion of a new form of parathyroid hormone (PTH) molecule, which can be detected by third-generation assays for PTH, but not by the second-generation assays. For the regression of already established nodular hyperplasia, the more advanced type of parathyroid hyperplasia, it is certainly necessary, in the near future, to develop new agents that specifically induce apoptosis in parathyroid cells. Until such agents are developed, prevention and early recognition of nodular hyperplasia is mandatory for the effective and safe management of hyperparathyroidism in CKD.
在慢性肾脏病（CKD）中，大多数患者会出现骨与矿物质代谢的多种异常。甲状旁腺在调节骨与矿物质代谢中起着非常重要的作用；因此，控制甲状旁腺功能是慢性肾脏病 - 矿物质和骨异常（CKD - MBD）管理的主要目标之一。在继发性甲状旁腺功能亢进的发生过程中，最近有研究表明成纤维细胞生长因子23（FGF23）起着关键作用，它既是一种排磷因子，也是肾脏中活性维生素D（1,25D）生成的抑制剂。FGF23最初分泌是为了预防CKD中的高磷血症，但这是以低1,25D和甲状旁腺功能亢进为代价的（重新审视“权衡”假说）。此外，最近的数据表明FGF23可能是甲状旁腺功能亢进预后的另一个有用标志物，因为血清高水平可能反映了先前给予的维生素D类似物的累积剂量。我们还证明，严重的甲状旁腺功能亢进与一种新型甲状旁腺激素（PTH）分子的产生和分泌有关，这种分子可以通过第三代PTH检测法检测到，但第二代检测法无法检测到。对于已经形成的结节性增生（甲状旁腺增生的更晚期类型）的消退，在不久的将来，开发能特异性诱导甲状旁腺细胞凋亡的新型药物肯定是必要的。在这类药物开发出来之前，预防和早期识别结节性增生对于CKD中甲状旁腺功能亢进的有效和安全管理至关重要。
