Seiler Sarah, Heine Gunnar H, Fliser Danilo
Department of Internal Medicine IV-Renal and Hypertensive Disease, Saarland University Medical Centre, Homburg/Saar, Germany.
Kidney Int Suppl. 2009 Dec(114):S34-42. doi: 10.1038/ki.2009.405.
Fibroblast growth factor (FGF)-23 is a recently discovered regulator of calcium-phosphate metabolism. Whereas other known FGFs mainly act in a paracrine manner, FGF-23 has significant systemic effects. Together with its cofactor Klotho, FGF-23 enhances renal phosphate excretion in order to maintain serum phosphate levels within the normal range. In patients with chronic kidney disease (CKD), FGF-23 levels rise in parallel with declining renal function long before a significant increase in serum phosphate concentration can be detected. However, in cross-sectional studies increased FGF-23 levels in patients with CKD were found to be associated not only with therapy-resistant secondary hyperparathyroidism but were also independently related to myocardial hypertrophy and endothelial dysfunction after adjustment for traditional markers of calcium-phosphate metabolism. Finally, in prospective studies high serum FGF-23 concentrations predicted faster disease progression in CKD patients not on dialysis, and increased mortality in patients receiving maintenance hemodialysis. FGF-23 may therefore prove to be an important therapeutic target in the management of CKD.
成纤维细胞生长因子(FGF)-23是最近发现的一种钙磷代谢调节剂。其他已知的成纤维细胞生长因子主要以旁分泌方式发挥作用,而成纤维细胞生长因子-23具有显著的全身效应。成纤维细胞生长因子-23与其辅助因子α-klotho一起,可增强肾脏排磷,从而将血清磷水平维持在正常范围内。在慢性肾脏病(CKD)患者中,早在血清磷浓度显著升高之前,成纤维细胞生长因子-23水平就随着肾功能下降而升高。然而,在横断面研究中发现,慢性肾脏病患者成纤维细胞生长因子-23水平升高不仅与治疗抵抗性继发性甲状旁腺功能亢进有关,而且在调整钙磷代谢的传统标志物后,还与心肌肥厚和内皮功能障碍独立相关。最后,在前瞻性研究中,高血清成纤维细胞生长因子-23浓度预示着未接受透析的慢性肾脏病患者疾病进展更快,以及接受维持性血液透析的患者死亡率增加。因此,成纤维细胞生长因子-23可能被证明是慢性肾脏病管理中的一个重要治疗靶点。