在血液透析患者中，骨硬化蛋白增加，而非 Dickkopf-1 蛋白，与脉搏波速度升高相关。

Increased Sclerostin, but Not Dickkopf-1 Protein, Is Associated with Elevated Pulse Wave Velocity in Hemodialysis Subjects.

机构信息

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece,

出版信息

Kidney Blood Press Res. 2019;44(4):679-689. doi: 10.1159/000501205. Epub 2019 Aug 5.

DOI:10.1159/000501205

PMID:31382263

Abstract

BACKGROUND

Sclerostin and Dickkopf-1 (Dkk-1) proteins are inhibitors of the canonical Wnt/β-catenin bone pathway. Pilot data suggest that sclerostin may be involved in vascular changes in chronic kidney disease (CKD), but data on the effects of Dkk-1 are scarce. This is the first study investigating simultaneously the associations of sclerostin and Dkk-1 with arterial stiffness in hemodialysis patients.

METHODS

A total of 80 patients on chronic hemodialysis had carotid-femoral pulse wave velocity (PWV), central blood pressure (BP), and wave reflections evaluated with applanation tonometry (Sphygmocor) on a midweek non-dialysis day. Serum levels of sclerostin and Dkk-1 were measured with ELISA. A large set of demographic, comorbid, laboratory, and drug parameters were used in the analyses.

RESULTS

Subjects with PWV >9.5 m/s (high arterial stiffness group, n = 40) were older, had higher BMI, higher prevalence of hypertension, diabetes, and coronary heart disease, and higher peripheral systolic BP, central systolic BP, C-reactive protein, and serum sclerostin (p = 0.02), but similar Dkk-1, compared to subjects with low PWV. When dichotomizing the population by sclerostin levels, those with high sclerostin had higher PWV than patients with low sclerostin levels (10.63 ± 2.71 vs. 9.77 ± 3.13, p = 0.048). Increased sclerostin (>200 pg/mL) was significantly associated with increased PWV (>9.5 m/s; HR 2.778, 95% CI 1.123-6.868 per pg/mL increase); this association remained significant after stepwise adjustment for Dkk-1, intact parathyroid hormone, and calcium × phosphate product. In contrast, no association was noted between Dkk-1 and PWV (HR 1.000, 95% CI 0.416-2.403).

CONCLUSION

Serum sclerostin is associated with PWV independently of routine markers of CKD-MBD in hemodialysis patients. In contrast, Dkk-1 has no association with arterial stiffness and is not pathophysiologically involved in relevant vascular changes.

摘要

背景

骨硬化蛋白（Sclerostin）和 Dickkopf-1（Dkk-1）蛋白是经典 Wnt/β-连环蛋白骨通路的抑制剂。初步研究表明，骨硬化蛋白可能与慢性肾脏病（CKD）中的血管变化有关，但关于 Dkk-1 的数据却很少。这是第一项研究，旨在同时探讨骨硬化蛋白和 Dkk-1 与血液透析患者动脉僵硬的相关性。

方法

在每周的非透析日，对 80 名接受慢性血液透析的患者进行颈股脉搏波速度（PWV）、中心血压（BP）和应用平板张力计（Sphygmocor）评估的波反射检测。采用 ELISA 法检测血清骨硬化蛋白和 Dkk-1 水平。在分析中使用了大量人口统计学、合并症、实验室和药物参数。

结果

PWV>9.5m/s（动脉僵硬组，n=40）的患者年龄较大，BMI 较高，高血压、糖尿病和冠心病的患病率较高，外周收缩压、中心收缩压、C 反应蛋白和血清骨硬化蛋白较高（p=0.02），但 Dkk-1 水平相似。当根据骨硬化蛋白水平将人群分为两组时，高骨硬化蛋白组的 PWV 高于低骨硬化蛋白组（10.63±2.71 vs. 9.77±3.13，p=0.048）。较高的骨硬化蛋白（>200pg/mL）与 PWV 升高（>9.5m/s；每增加 1pg/mL，HR 2.778，95%CI 1.123-6.868）显著相关；在逐步调整 Dkk-1、全段甲状旁腺激素和钙×磷乘积后，这种相关性仍然显著。相比之下，Dkk-1 与 PWV 之间无相关性（HR 1.000，95%CI 0.416-2.403）。