Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece,
Kidney Blood Press Res. 2019;44(4):679-689. doi: 10.1159/000501205. Epub 2019 Aug 5.
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.
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.
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).
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.
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。
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。
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）。
血清骨硬化蛋白与血液透析患者的 CKD-MBD 常规标志物独立相关。相反，Dkk-1 与动脉僵硬无相关性，并且与相关血管变化在病理生理学上无关联。
