Department of Pediatrics, Tokushima University Graduate School of Biomedical Sciences, Kuramoto-cho 3-18-15, Tokushima, Tokushima, 770-8503, Japan.
Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan.
Pediatr Nephrol. 2023 Nov;38(11):3711-3719. doi: 10.1007/s00467-023-06026-5. Epub 2023 May 25.
The current study tested the hypothesis that urinary angiotensinogen (UAGT) and urinary monocyte chemoattractant protein-1 (UMCP-1) levels provide a specific index of intrarenal renin-angiotensin system (RAS) status and the degree of infiltration of macrophages associated with RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis.
We measured baseline UAGT and UMCP-1 levels to examine the correlation between glomerular injury in 48 pediatric chronic glomerulonephritis patients before treatment. Furthermore, we performed immunohistochemical analysis of angiotensinogen (AGT) and CD68 in 27 pediatric chronic glomerulonephritis patients treated with RAS blockades and immunosuppressants for 2 years. Finally, we examined the effects of angiotensin II (Ang II) on monocyte chemoattractant protein-1 (MCP-1) expression in cultured human mesangial cells (MCs).
Baseline UAGT and UMCP-1 levels positively correlated with urinary protein levels, scores for mesangial hypercellularity, rate of crescentic formation, and expression levels of AGT and CD68 in renal tissues (p < 0.05). UAGT and UMCP-1 levels were significantly decreased after RAS blockade and immunosuppressant treatment (p < 0.01), which was accompanied by AGT and CD68 (p < 0.01), as well as the magnitude of glomerular injury. Cultured human MCs showed increased MCP-1 messenger ribonucleic acid and protein levels after Ang II treatment (p < 0.01).
The data indicates that UAGT and UMCP-1 are useful biomarkers of the degree of glomerular injury during RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis.
本研究旨在检验以下假设,即尿血管紧张素原(UAGT)和尿单核细胞趋化蛋白-1(UMCP-1)水平为肾内肾素-血管紧张素系统(RAS)状态和与 RAS 阻断及免疫抑制剂治疗相关的巨噬细胞浸润程度提供特异性指标。
我们测量了 48 例小儿慢性肾小球肾炎患者治疗前的 UAGT 和 UMCP-1 基线水平,以检查肾小球损伤与这些水平之间的相关性。此外,我们对 27 例接受 RAS 阻断和免疫抑制剂治疗 2 年的小儿慢性肾小球肾炎患者进行了血管紧张素原(AGT)和 CD68 的免疫组织化学分析。最后,我们检测了血管紧张素 II(Ang II)对培养的人肾小球系膜细胞(MCs)中单核细胞趋化蛋白-1(MCP-1)表达的影响。
UAGT 和 UMCP-1 基线水平与尿蛋白水平、系膜细胞增生评分、新月体形成率、肾组织中 AGT 和 CD68 的表达水平呈正相关(p<0.05)。RAS 阻断和免疫抑制剂治疗后 UAGT 和 UMCP-1 水平显著降低(p<0.01),同时伴有 AGT 和 CD68 水平的降低(p<0.01),以及肾小球损伤程度的降低。Ang II 处理后培养的人 MCs 的 MCP-1 信使核糖核酸和蛋白水平增加(p<0.01)。
这些数据表明,UAGT 和 UMCP-1 是小儿慢性肾小球肾炎患者接受 RAS 阻断和免疫抑制剂治疗期间肾小球损伤程度的有用生物标志物。