A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease.
A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease.
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DOI：
10.1371/journal.pone.0056695
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Makino H
中科院分区：
文献类型：
--
作者：
Kitagawa M;Sugiyama H;Morinaga H;Inoue T;Takiue K;Ogawa A;Yamanari T;Kikumoto Y;Uchida HA;Kitamura S;Maeshima Y;Nakamura K;Ito H;Makino H
Klotho最初是在一种无法表达该基因的突变小鼠品系中发现的，这种突变小鼠品系因此显示出寿命缩短。在人类中，低血清Klotho水平与社区居住成年人心血管疾病的患病率有关。然而，目前尚不清楚血清Klotho水平是否与慢性肾病（CKD）患者的血管功能障碍体征（如动脉僵硬度）相关，这是预后的主要决定因素。我们采用ELISA法测定了114例CKD患者血清中可溶性Klotho的水平，并研究了Klotho水平与CKD-矿物质和骨疾病（CKD-MBD）标志物和各种血管功能障碍之间的关系，包括血流介导的扩张，内皮功能障碍的标志物，踝臂脉搏波速度（baPWV），动脉僵硬度的标志物，内膜中层厚度（IMT），动脉粥样硬化的标志物，以及主动脉钙化指数（ACI），血管钙化的标志物。血清Klotho水平与1，25-二羟维生素D水平显著相关，与甲状旁腺激素水平和磷酸盐排泄分数呈负相关。动脉硬化定义为baPWV≥1400 cm/sec，动脉粥样硬化定义为最大IMT≥1.1 mm，血管钙化评分ACI> 0%的患者血清Klotho显著降低。在代谢模型、CKD模型或CKD-MBD模型的多变量分析中，血清Klotho水平是动脉僵硬度的重要决定因素，而不是内皮功能障碍、动脉粥样硬化或血管钙化。baPWV的血清Klotho校正比值比为0.60（p = 0.0075）。 血清可溶性Klotho水平的降低与CKD患者的血管功能障碍体征（如动脉僵硬）独立相关。进一步研究探索维持或升高Klotho水平的治疗方法是否可以改善CKD患者的动脉僵硬度是必要的。
Klotho was originally identified in a mutant mouse strain unable to express the gene that consequently showed shortened life spans. In humans, low serum Klotho levels are related to the prevalence of cardiovascular diseases in community-dwelling adults. However, it is unclear whether the serum Klotho levels are associated with signs of vascular dysfunction such as arterial stiffness, a major determinant of prognosis, in human subjects with chronic kidney disease (CKD). We determined the levels of serum soluble Klotho in 114 patients with CKD using ELISA and investigated the relationship between the level of Klotho and markers of CKD-mineral and bone disorder (CKD-MBD) and various types of vascular dysfunction, including flow-mediated dilatation, a marker of endothelial dysfunction, ankle-brachial pulse wave velocity (baPWV), a marker of arterial stiffness, intima-media thickness (IMT), a marker of atherosclerosis, and the aortic calcification index (ACI), a marker of vascular calcification. The serum Klotho level significantly correlated with the 1,25-dihydroxyvitamin D level and inversely correlated with the parathyroid hormone level and the fractional excretion of phosphate. There were significant decreases in serum Klotho in patients with arterial stiffness defined as baPWV≥1400 cm/sec, atherosclerosis defined as maximum IMT≥1.1 mm and vascular calcification scores of ACI>0%. The serum Klotho level was a significant determinant of arterial stiffness, but not endothelial dysfunction, atherosclerosis or vascular calcification, in the multivariate analysis in either metabolic model, the CKD model or the CKD-MBD model. The adjusted odds ratio of serum Klotho for the baPWV was 0.60 (p = 0.0075). Decreases in the serum soluble Klotho levels are independently associated with signs of vascular dysfunction such as arterial stiffness in patients with CKD. Further research exploring whether therapeutic approaches to maintain or elevate the Klotho level could improve arterial stiffness in CKD patients is warranted.
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DOI：
10.1006/bbrc.2000.4226
发表时间：
2001-02-02
影响因子：
3.1
作者：
Koh, N;Fujimori, T;Nabeshima, Y
通讯作者：
Nabeshima, Y
影响因子：
6.1
作者：
Komaba, Hirotaka;Koizumi, Masahiro;Fukagawa, Masafumi
通讯作者：
Fukagawa, Masafumi
影响因子：
13.6
作者：
Kestenbaum, B;Sampson, JN;Andress, DL
通讯作者：
Andress, DL
影响因子：
6.1
作者：
Hanada, Shigeru;Ando, Ryoichi;Sasaki, Sei
通讯作者：
Sasaki, Sei
影响因子：
8.3
作者：
HANDA, N;MATSUMOTO, M;KAMADA, T
通讯作者：
KAMADA, T