Delgado Graciela E, Kleber Marcus E, Scharnagl Hubert, Krämer Bernhard K, März Winfried, Scherberich Jürgen E
Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
J Am Soc Nephrol. 2017 Jul;28(7):2201-2210. doi: 10.1681/ASN.2016111162. Epub 2017 Feb 27.
The mucoprotein uromodulin is the most abundant protein in mammalian urine and has important roles in ion transport, maintenance of water and electrolyte balance, and clearance of bacteria from the urinary tract. Low urinary uromodulin concentrations have been associated with increased mortality risk. However, measuring uromodulin in urine has several preanalytic drawbacks, and sensitive assays for the detection of uromodulin in blood have become available. In this study, we investigated the association of serum uromodulin concentration with cardiovascular biomarkers and mortality risk in a large cohort of patients referred for coronary angiography. Uromodulin concentrations were available in 3057 of 3316 participants of the Ludwigshafen Risk and Cardiovascular Health Study. Higher serum uromodulin concentration associated with a favorable metabolic profile, lower prevalence rates of comorbidities (arterial hypertension, diabetes mellitus, and heart failure), and a lower risk for 10-year mortality, with hazard ratios (95% confidence intervals) of 0.65 (0.54 to 0.78), 0.71 (0.58 to 0.88), and 0.57 (0.45 to 0.73) in the second, third, and fourth quartiles, respectively, compared with the first quartile. The association with reduced mortality was independent of other cardiovascular risk factors, including eGFR, and stronger after adjustment for the genotype of the rs12917707 polymorphism at the locus. Adding serum uromodulin concentration to established cardiovascular risk prediction scores improved risk prediction. Uromodulin may, therefore, be a useful marker for cardiovascular and renal health.
黏蛋白尿调节素是哺乳动物尿液中含量最丰富的蛋白质,在离子转运、维持水和电解质平衡以及清除泌尿道细菌方面发挥着重要作用。低尿调节素浓度与死亡风险增加有关。然而,检测尿液中的尿调节素存在几个分析前的缺点,并且已经有了检测血液中尿调节素的灵敏检测方法。在本研究中,我们在一大群因冠状动脉造影而转诊的患者中,研究了血清尿调节素浓度与心血管生物标志物及死亡风险之间的关联。路德维希港风险与心血管健康研究的3316名参与者中,有3057人的尿调节素浓度数据可用。血清尿调节素浓度较高与良好的代谢状况、较低的合并症(动脉高血压、糖尿病和心力衰竭)患病率以及较低的10年死亡风险相关,与第一四分位数相比,第二、第三和第四四分位数的风险比(95%置信区间)分别为0.65(0.54至0.78)、0.71(0.58至0.88)和0.57(0.45至0.73)。与死亡率降低的关联独立于其他心血管危险因素,包括估算肾小球滤过率(eGFR),并且在对该位点rs12917707多态性的基因型进行调整后更强。将血清尿调节素浓度纳入既定的心血管风险预测评分可改善风险预测。因此,尿调节素可能是心血管和肾脏健康的有用标志物。