Urinary angiotensinogen reflects the activity of intrarenal renin-angiotensin system in patients with IgA nephropathy
Urinary angiotensinogen reflects the activity of intrarenal renin-angiotensin system in patients with IgA nephropathy
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DOI：
10.1093/ndt/gfq371
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发表时间：
2011-01-01
影响因子：
6.1
通讯作者：
Imanishi, Masahito
中科院分区：
文献类型：
--
作者：
Nishiyama, Akira;Konishi, Yoshio;Imanishi, Masahito
背景血管紧张素II（AngII）受体阻滞剂（ARB）的血压非依赖性肾保护作用证据表明，局部激活的肾素-血管紧张素系统（RAS）可能导致肾损伤的发病机制。本研究旨在验证尿血管紧张素原是免疫球蛋白A（伊加）肾病患者肾内RAS状态的特异性指标这一假设。本文对三组尿液样本进行了调查：健康志愿者、伊加肾病患者和轻微肾小球异常（MGA）患者。本研究排除了高血压、糖尿病、肾小球滤过率降低和/或正在接受任何药物治疗的患者。采用双抗体夹心酶联免疫吸附法测定尿血管紧张素原水平。尿血管紧张素原水平在健康志愿者和MGA患者之间没有差异。然而，尿血管紧张素原水平，肾组织血管紧张素原表达和血管紧张素Ⅱ免疫反应性显着高于伊加肾病患者比MGA患者。基线尿血管紧张素原水平与肾血管紧张素原基因表达和AngII免疫反应性呈正相关，但与血浆肾素活性或尿蛋白排泄率无关。在伊加肾病患者中，ARB缬沙坦（40 mg/天）治疗可显着增加肾血浆流量并降低滤过分数，这与尿血管紧张素原水平的降低有关。结论。这些数据表明，尿血管紧张素原是一个强有力的工具，以确定肾内RAS状态和相关的肾功能紊乱的伊加肾病患者。
Background. A potential contribution of local activation of the renin-angiotensin system (RAS) to the pathogenesis of renal injury has been indicated by evidence for blood pressure-independent renoprotective effects of angiotensin II (AngII) receptor blockers (ARBs). The present study was performed to test the hypothesis that urinary angiotensinogen provides a specific index of intrarenal RAS status in patients with immunoglobulin A (IgA) nephropathy.Methods. This paper is a survey of urine specimens from three groups: healthy volunteers, patients with IgA nephropathy and patients with minor glomerular abnormality (MGA). Patients with hypertension, diabetes, reduced glomerular filtration rate and/or who were under any medication were excluded from this study. Urinary angiotensinogen levels were measured by a sandwich enzyme-linked immunosorbent assay system.Results. Urinary angiotensinogen levels were not different between healthy volunteers and patients with MGA. However, urinary angiotensinogen levels, renal tissue angiotensinogen expression and AngII immunoreactivity were significantly higher in patients with IgA nephropathy than in patients with MGA. Baseline urinary angiotensinogen levels were positively correlated with renal angiotensinogen gene expression and AngII immunoreactivity but not with plasma renin activity or the urinary protein excretion rate. In patients with IgA nephropathy, treatment with an ARB, valsartan (40 mg/day), significantly increased renal plasma flow and decreased filtration fraction, which were associated with reductions in urinary angiotensinogen levels.Conclusion. These data indicate that urinary angiotensinogen is a powerful tool for determining intrarenal RAS status and associated renal derangement in patients with IgA nephropathy.