慢性肾脏病患者血管钙化的病理机制研究进展

Research Progress in Pathological Mechanism of Vascular Calcification in Patients with Chronic Kidney Disease

关键词:  慢性肾脏病  血管钙化  成纤维细胞生长因子-23  高磷血症  脂联素

Key words:  chronic kidney disease  vascular calcification  fibroblast growth factor-23  hyperphosphatemia  adiponectin

摘要:

在慢性肾脏病（chronic kidney disease，CKD）患者中，肾功能的进行性降低导致矿物质代谢紊乱、酸中毒、营养不良、炎症和尿毒症毒素积累等症状，可引起继发性甲状旁腺功能亢进、血清钙升高、磷酸盐水平升高和血清成纤维细胞生长因子-23（fibroblast growth factor-23，FGF-23）升高，由此产生CKD相关的矿物质和骨代谢紊乱，循环中过量的钙和磷酸盐也可以促进蛋白质-矿物质复合物的形成，称为钙蛋白颗粒（calpain particles，CPPs），在CKD中，这些CPPs含有较少的钙化抑制剂，诱发炎症，并促进血管平滑肌细胞的钙化。由此促进血管钙化的发生。诸多横断面观察研究表明，血清FGF-23水平在CKD早期（1~2期）开始升高，并与肾小球滤过率呈负相关，促进血管钙化，最新的研究表明高水平脂联素对FGF-23在冠状动脉钙化的作用中起调节作用。本文综述了CKD患者血管钙化发展机制的研究进展，为进一步寻找潜在的新治疗目标指出方向。

Abstract:

In patients with chronic kidney disease(CKD), progressive deterioration of renal function leads to mineral metabolism disorders, acidosis, malnutrition, inflammation and accumulation of uremic toxins, which can cause secondary hyperparathyroidism and elevated serum calcium. Increased phosphate levels and elevated serum fibroblast growth factor-23 (FGF-23), resulting in CKD-related mineral and bone metabolism disorders, excess calcium and phosphate in the circulation can also promote protein-mineral complex called calpain particles(CPPs). In CKD, these CPPs contain little calcification inhibitors, induce inflammation, and promote calcification of vascular smooth muscle cells, thereby promoting the occurrence of vascular calcification. Many cross-sectional observation studies have shown that blood FGF-23 levels begin to increase in the early stage of CKD(stage 1-2) and are negatively correlated with glomerular filtration rate, promoting vascular calcification. The latest research indicates high levels of adiponectin plays a role in the effect of FGF23 on coronary artery calcification. This article reviews the research progress in the mechanism of vascular calcification in patients with CKD, and points out the direction for further search for potential new therapeutic goals.