Urushihara Maki, Nagai Takashi, Kinoshita Yukiko, Nishiyama Sato, Suga Kenichi, Ozaki Natsuko, Jamba Ariunbold, Kondo Shuji, Kobori Hiroyuki, Kagami Shoji
Department of Pediatrics, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan,
Pediatr Nephrol. 2015 Jun;30(6):975-82. doi: 10.1007/s00467-014-3028-8. Epub 2014 Dec 20.
Recently, we demonstrated that urinary angiotensinogen (AGT) levels are increased and reflect intrarenal renin-angiotensin system (RAS) status in pediatric patients with chronic glomerulonephritis. Therefore, this study was performed to test the hypothesis that urinary AGT (UAGT) levels provide a specific index of intrarenal RAS status associated with RAS blockade treatment in pediatric IgA nephropathy (IgAN) patients.
We measured plasma and UAGT levels and urinary transforming growth factor beta (TGF-β) levels, after which we performed immunohistochemical analysis of AGT, angiotensin II (Ang II), and TGF-β in 24 pediatric IgAN patients treated with RAS blockades for 2 years. Paired tests were used to analyze the changes from baseline to study end.
Although there was no change in plasma AGT levels, UAGT and TGF-β levels were significantly decreased after RAS blockade, which was accompanied by the expression levels of AGT, Ang II, and TGF-β, as well as the magnitude of glomerular injury. Baseline UAGT levels positively correlated with diastolic blood pressure, urinary protein levels, scores for mesangial hypercellularity, and the expression levels of AGT, Ang II, and TGF-β in renal tissues.
These data indicate that UAGT is a useful biomarker of intrarenal RAS activation, which is associated with glomerular injury during RAS blockade in pediatric IgAN patients.
最近，我们证明了慢性肾小球肾炎患儿尿血管紧张素原（AGT）水平升高，并反映肾内肾素-血管紧张素系统（RAS）状态。因此，本研究旨在验证以下假设：尿AGT（UAGT）水平可作为小儿IgA肾病（IgAN）患者肾内RAS状态的一个特定指标，该指标与RAS阻断治疗相关。
我们测量了血浆和UAGT水平以及尿转化生长因子β（TGF-β）水平，之后对24例接受RAS阻断治疗2年的小儿IgAN患者进行了AGT、血管紧张素II（Ang II）和TGF-β的免疫组化分析。采用配对检验分析从基线到研究结束时的变化。
虽然血浆AGT水平没有变化，但RAS阻断后UAGT和TGF-β水平显著降低，同时伴有AGT、Ang II和TGF-β的表达水平以及肾小球损伤程度的降低。基线UAGT水平与舒张压、尿蛋白水平、系膜细胞增生评分以及肾组织中AGT、Ang II和TGF-β的表达水平呈正相关。
这些数据表明，UAGT是肾内RAS激活的一个有用生物标志物，与小儿IgAN患者RAS阻断期间的肾小球损伤相关。
