Fetuin-Mineral Complex Reflects Extraosseous Calcification Stress in CKD
Fetuin-Mineral Complex Reflects Extraosseous Calcification Stress in CKD
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DOI：
10.1681/asn.2009090944
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发表时间：
2010-11-01
影响因子：
13.6
通讯作者：
Isaka, Yoshitaka
中科院分区：
文献类型：
--
作者：
Hamano, Takayuki;Matsui, Isao;Isaka, Yoshitaka
胎球蛋白 A 是骨外钙化的重要抑制剂，但一些使用 ELISA 的研究并未发现慢性肾病 (CKD) 患者血清胎球蛋白 A 水平与血管钙化之间存在显着关系。在此，我们采用离心法从血液透析患者的血清中分离出由胎球蛋白 A 纤维蛋白原纤连蛋白 1 和钙组成的胎球蛋白-矿物质复合物 (FMC)。此外，我们还分析了血液透析患者的血清胎球蛋白 A 水平。 73 名患有糖尿病和 CKD（透析前）的患者离心后，上清液中的胎球蛋白 A 浓度显着低于 CKD 任何阶段患者血清中的浓度，表明这些患者中存在 FMC。随着 CKD 的严重程度增加，FMC 对总胎球蛋白 A 的贡献增加。离心降低的胎球蛋白 A（降低率 [RR]）与 CACS 呈正相关 在一项针对 12 名继发性甲状旁腺功能亢进症的血液透析患者的纵向研究中，甲状旁腺切除术和西那卡塞治疗均在 1 个月后显着降低 RR，而不改变上清液胎球蛋白 A 水平，表明 FMC 降低。此外，西那卡塞诱导的甲状旁腺激素降低程度与 RR 降低相关，但与血清或上清液胎蛋白变化无关A 这些数据表明，FMC 的定量测量（而不是之前研究中测量的上清液或血清胎球蛋白 A）反映了骨外钙化应激
Fetuin A is an important inhibitor of extraosseous calcification, but some of the studies that used ELISAs did not identify a significant relationship between serum fetuin A levels and vascular calcification in patients with chronic kidney disease (CKD) Here, we used centrifugation to separate a fetuin-mineral complex (FMC) composed of fetuin-A fibrinogen fibronectin 1 and calcium from the serum of hemodialysis patients In addition we analyzed serum fetuin A levels of 73 patients with diabetes and CKD (predialysis) after centrifugation Fetuin-A concentrations were significantly lower in supernatants than in serum from patients at any stage of CKD indicating systemic circulation of FMC in these patients With greater severity of CKD the contribution of FMC to total fetuin A increased Despite the absence of a correlation between serum fetuin A and coronary artery calcification scores (CACS), supernatant fetuin-A negatively correlated with CACS and the extent to which centrifugation reduced fetuin A (reduction ratio [RR]) positively correlated with CACS In a longitudinal study of 12 hemodialysis patients with secondary hyperparathyroidism, parathyroidectomy and cinacalcet therapy each significantly reduced the RR without changing supernatant fetuin-A levels after 1 month, suggesting a reduction in FMC Moreover, the magnitude of cinacalcet-induced reduction in parathyroid hormone correlated with the decrease in RR but not with changes in serum or supernatant fetuin A These data suggest that a quantitative measure of FMC, not supernatant or serum fetuin A as measured in previous studies, reflects extraosseous calcification stress