Urinary angiotensinogen as a novel biomarker of the intrarenal renin-angiotensin system status in hypertensive patients.
Urinary angiotensinogen as a novel biomarker of the intrarenal renin-angiotensin system status in hypertensive patients.
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DOI：
10.1161/hypertensionaha.108.123802
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Navar LG
中科院分区：
文献类型：
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作者：
Kobori H;Alper AB Jr;Shenava R;Katsurada A;Saito T;Ohashi N;Urushihara M;Miyata K;Satou R;Hamm LL;Navar LG
我们以前报道过尿血管紧张素原（UAGT）水平是血管紧张素II依赖性高血压大鼠肾内肾素-血管紧张素系统（RAS）状态的一个特异性指标。为了在人类中研究这一系统，我们最近开发了一种人类血管紧张素原ELISA。为了验证高血压患者UAGT增加的假设，我们招募了110名成年人。4例估计肾小球滤过水平< 30ml /min / 1.73 m2的受试者被排除，因为先前的研究已经表明UAGT与慢性肾病这一阶段估计的肾小球滤过高度相关。因此，我们分析了70例高血压患者（39例使用RAS受体阻滞剂[血管紧张素转换酶抑制剂或血管紧张素II型受体阻滞剂；收缩压：139±3mmhg]， 31例未使用RAS受体阻滞剂[收缩压：151±4mmhg]）和36例正常血压患者（收缩压：122±2mmhg）的106对尿液和血浆样本。尿肌酐浓度标准化的UAGT与种族、性别、年龄、身高、体重、体重指数、钠排泄分数、血浆血管紧张素原水平或估计的肾小球滤过率无关。UAGT/尿肌酐浓度与收缩压、舒张压、尿白蛋白：肌酐比（r=0.5994）、尿蛋白：肌酐比（r=0.4597）呈显著正相关。未使用RAS受体阻滞剂的高血压患者UAGT/尿肌酐浓度（25.00±4.96 μg）明显高于正常血压组（13.70±2.33 μg）。重要的是，接受RAS阻滞剂治疗的患者表现出这种增强的显著衰减（13.26±2.60 μg/g）。这些数据表明高血压患者的UAGT升高，而RAS阻滞剂治疗可抑制UAGT，提示RAS阻断降低肾内RAS活性的效果可通过测量UAGT来评估。
We reported previously that urinary angiotensinogen (UAGT) levels provide a specific index of the intrarenal renin-angiotensin system (RAS) status in angiotensin II– dependent hypertensive rats. To study this system in humans, we recently developed a human angiotensinogen ELISA. To test the hypothesis that UAGT is increased in hypertensive patients, we recruited 110 adults. Four subjects with estimated glomerular filtration levels <30 mL/min per 1.73 m2 were excluded because previous studies have already shown that UAGT is highly correlated with estimated glomerular filtration in this stage of chronic kidney disease. Consequently, 106 paired samples of urine and plasma were analyzed from 70 hypertensive patients (39 treated with RAS blockers [angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers; systolic blood pressure: 139±3 mm Hg] and 31 not treated with RAS blockers [systolic blood pressure: 151±4 mm Hg]) and 36 normotensive subjects (systolic blood pressure: 122±2 mm Hg). UAGT, normalized by urinary concentrations of creatinine, were not correlated with race, gender, age, height, body weight, body mass index, fractional excretion of sodium, plasma angiotensinogen levels, or estimated glomerular filtration. However, UAGT/urinary concentration of creatinine was significantly positively correlated with systolic blood pressure, diastolic blood pressure, urinary albumin:creatinine ratio (r=0.5994), and urinary protein:creatinine ratio (r=0.4597). UAGT/urinary concentration of creatinine was significantly greater in hypertensive patients not treated with RAS blockers (25.00±4.96 μg/g) compared with normotensive subjects (13.70±2.33 μg/g). Importantly, patients treated with RAS blockers exhibited a marked attenuation of this augmentation (13.26±2.60 μg/g). These data indicate that UAGT is increased in hypertensive patients, and treatment with RAS blockers suppresses UAGT, suggesting that the efficacy of RAS blockade to reduce the intrarenal RAS activity can be assessed by measurements of UAGT.