Suliman Mohamed E, García-López Elvia, Anderstam Björn, Lindholm Bengt, Stenvinkel Peter
Department of Clinical Science, Intervention and Technology, Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
Adv Clin Chem. 2008;46:217-62. doi: 10.1016/s0065-2423(08)00406-x.
The mortality rate is extremely high in chronic kidney disease (CKD), primarily due to the high prevalence of cardiovascular disease (CVD) in this patient group. Apart from traditional Framingham risk factors, evidences suggest that nontraditional risk factors, such as inflammation, oxidative stress, endothelial dysfunction, and vascular calcification also contribute to this extremely high risk of CVD. Disturbance in the mineral metabolism, especially in the ions of Ca and PO4, are linked to enhanced calcification of blood vessels. Although the mechanism(s) of this enhanced calcification process are not fully understood, current knowledge suggests that a large number (and an imbalance between them) of circulating promoters and inhibitors of the calcification process, that is, fetuin-A (or alpha 2-Heremans-Schmid glycoprotein, AHSG), matrix-Gla protein (MGP), osteoprotegerin (OPG), osteopontin (OPN), bone morphogenetic proteins (BMPs), and inorganic pyrophosphate (PPi), are involved in the deterioration of vascular tissue. Thus, an imbalance in these factors may contribute to the high prevalence of vascular complications in CKD patients. Among these mediators, studies on fetuin-A deserve further attention as clinical studies consistently show that fetuin-A deficiency is associated with vascular calcification, all-cause and cardiovascular mortality in CKD patients. Both chronic inflammation and the uremic milieu per se may contribute to fetuin-A depletion, as well as specific mutations in the AHSG gene. Recent experimental and clinical studies also suggest an intriguing link between fetuin-A, insulin resistance, and the metabolic syndrome.
慢性肾脏病（CKD）的死亡率极高，主要原因是该患者群体中心血管疾病（CVD）的高患病率。除了传统的弗雷明汉风险因素外，有证据表明，非传统风险因素，如炎症、氧化应激、内皮功能障碍和血管钙化，也导致了CVD的极高风险。矿物质代谢紊乱，尤其是钙和磷酸根离子的紊乱，与血管钙化增强有关。尽管这种钙化增强过程的机制尚未完全明了，但目前的知识表明，大量（且它们之间存在失衡）的循环钙化过程促进剂和抑制剂，即胎球蛋白-A（或α2-赫曼斯-施密德糖蛋白，AHSG）、基质Gla蛋白（MGP）、骨保护素（OPG）、骨桥蛋白（OPN）、骨形态发生蛋白（BMP）和无机焦磷酸盐（PPi），参与了血管组织的恶化。因此，这些因素的失衡可能导致CKD患者血管并发症的高患病率。在这些介质中，对胎球蛋白-A的研究值得进一步关注，因为临床研究一致表明，胎球蛋白-A缺乏与CKD患者的血管钙化、全因死亡率和心血管死亡率相关。慢性炎症和尿毒症环境本身都可能导致胎球蛋白-A的消耗，以及AHSG基因的特定突变。最近的实验和临床研究还表明，胎球蛋白-A、胰岛素抵抗和代谢综合征之间存在有趣的联系。
