Kobori Hiroyuki, Alper A Brent, Shenava Rajesh, Katsurada Akemi, Saito Toshie, Ohashi Naro, Urushihara Maki, Miyata Kayoko, Satou Ryousuke, Hamm L Lee, Navar L Gabriel
Department of Medicine, Renal Center of Excellence, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112-2699, USA.
Hypertension. 2009 Feb;53(2):344-50. doi: 10.1161/HYPERTENSIONAHA.108.123802. Epub 2008 Dec 15.
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 m(2) 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 microg/g) compared with normotensive subjects (13.70+/-2.33 microg/g). Importantly, patients treated with RAS blockers exhibited a marked attenuation of this augmentation (13.26+/-2.60 microg/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.
我们之前报道过，在血管紧张素II依赖性高血压大鼠中，尿血管紧张素原（UAGT）水平可作为肾内肾素-血管紧张素系统（RAS）状态的一个特异性指标。为了在人类中研究该系统，我们最近开发了一种人血管紧张素原酶联免疫吸附测定法（ELISA）。为了验证高血压患者UAGT升高这一假设，我们招募了110名成年人。4名估计肾小球滤过水平<30 mL/（min·1.73 m²）的受试者被排除，因为之前的研究已经表明，在慢性肾病的这个阶段，UAGT与估计肾小球滤过高度相关。因此，我们分析了来自70名高血压患者（39名接受RAS阻滞剂治疗[血管紧张素转换酶抑制剂或血管紧张素II 1型受体阻滞剂；收缩压：139±3 mmHg]和31名未接受RAS阻滞剂治疗[收缩压：151±4 mmHg]）以及36名血压正常受试者（收缩压：122±2 mmHg）的106对尿液和血浆样本。经尿肌酐浓度标准化后的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肾小球滤过均无相关性。然而，UAGT/尿肌酐浓度与收缩压、舒张压、尿白蛋白：肌酐比值（r = 0.5994）以及尿蛋白：肌酐比值（r = 0.4597）显著正相关。未接受RAS阻滞剂治疗的高血压患者的UAGT/尿肌酐浓度（25.00±4.96 μg/g）显著高于血压正常受试者（13.70±2.33 μg/g）。重要的是，接受RAS阻滞剂治疗的患者这种升高明显减弱（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，这表明通过测量UAGT可评估RAS阻断降低肾内RAS活性的疗效。
