Leiherer Andreas, Muendlein Axel, Saely Christoph H, Ebner Janine, Brandtner Eva M, Fraunberger Peter, Drexel Heinz
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Medical Central Laboratories, Feldkirch, Austria.
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
Int J Cardiol. 2017 Mar 15;231:6-12. doi: 10.1016/j.ijcard.2016.12.183. Epub 2016 Dec 29.
Uromodulin is a protein produced exclusively by the kidneys and present in urine and blood. In contrast to weak and in part contradictory study data on uromodulin in urine samples, the analysis of serum samples recently proved uromodulin's value as superior biomarker for ongoing kidney disease. Whether serum uromodulin is associated with cardiovascular event risk and whether it has predictive power for overall mortality is still unknown and has been evaluated in the present study.
We measured uromodulin in a series of 529 patients without acute coronary syndrome undergoing coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD) and prospectively recorded mortality as well as cardiovascular events in our patients during a follow-up of up to 8years.
We recorded 95 deaths and 145 cardiovascular events over 8years. Serum uromodulin proved protective for overall mortality (HR=0.56 [95%CI 0.43-0.72]; p<0.001), even after full adjustment including eGFR, current smoking, diabetes, and CAD status (adj. HR=0.57 [95%CI 0.37-0.89]; p=0.014). Patients in the lowest tertile of serum uromodulin had a significantly higher cardiovascular event risk compared to patients in the medium and highest tertile (HR=of 1.45 (95%CI 1.04-2.02, p=0.027). The ratio between creatinine and uromodulin was significantly associated with kidney function (r=-0.322; p<0.001) and significantly predicted the incidence of cardiovascular events (HR of 1.26 [95%CI 1.12-1.41], p<0.001) and major cardiovascular events (HR of 1.37 [95%CI 1.21-1.56], p<0.001).
We conclude that serum uromodulin is a valuable biomarker to predict overall mortality and cardiovascular events.
尿调节蛋白是一种仅由肾脏产生的蛋白质,存在于尿液和血液中。与尿液样本中关于尿调节蛋白的微弱且部分相互矛盾的研究数据不同,近期对血清样本的分析证明尿调节蛋白作为正在发生的肾脏疾病的卓越生物标志物具有重要价值。血清尿调节蛋白是否与心血管事件风险相关以及它对总体死亡率是否具有预测能力仍然未知,本研究对此进行了评估。
我们对529例无急性冠状动脉综合征且接受冠状动脉造影以评估已确诊或疑似稳定冠状动脉疾病(CAD)的患者进行了尿调节蛋白测量,并在长达8年的随访期间前瞻性记录了患者的死亡率以及心血管事件。
在8年期间,我们记录了95例死亡和145例心血管事件。血清尿调节蛋白被证明对总体死亡率具有保护作用(HR = 0.56 [95%CI 0.43 - 0.72];p < 0.001),即使在进行全面调整(包括估算肾小球滤过率、当前吸烟情况、糖尿病和CAD状态)后也是如此(调整后HR = 0.57 [95%CI 0.37 - 0.89];p = 0.014)。血清尿调节蛋白处于最低三分位数的患者与处于中等和最高三分位数的患者相比,心血管事件风险显著更高(HR = 1.45 [95%CI 1.04 - 2.02,p = 0.027])。肌酐与尿调节蛋白的比值与肾功能显著相关(r = -0.322;p < 0.001),并显著预测心血管事件的发生率(HR = 1.26 [95%CI 1.12 - 1.41],p < 0.001)和主要心血管事件(HR = 1.37 [95%CI 1.21 - 1.56],p < 0.001)。
我们得出结论,血清尿调节蛋白是预测总体死亡率和心血管事件的有价值生物标志物。