Department of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
Department of Pediatric Surgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
Int Urol Nephrol. 2020 Apr;52(4):603-610. doi: 10.1007/s11255-019-02357-1. Epub 2019 Dec 12.
To investigate the urinary levels of TGF-β1, VEGF, and MCP-1 as potential biomarkers of latent inflammation and fibrosis in the kidney before and 6 months after correction of vesicoureteral reflux (VUR) in children.
A total of 88 patients (mean age 26 months) with VUR were divided into three groups: group A-patients with grades II-III VUR, conservative treatment; group B-patients with grades III-V VUR, endoscopic correction of VUR; group C-patients with grades III-V VUR, ureteral reimplantation after failed endoscopic correction. Control group included 20 healthy children. Biomarker levels were measured by ELISA. Tc-DMSA scintigraphy and renal histology were performed if possible.
At admission, TGF-β1 was close to control in all study groups, VEGF increased with severity of the disease, and MCP-1 increased in group C. Six months after correction of VUR, despite clinical and laboratory improvement, TGF-β1 and MCP-1 increased while VEGF decreased compared to the admission values in all groups; no amelioration of renal scarring was detected either by Tc-DMSA scintigraphy or renal histology.
The results support our hypothesis that successful correction of VUR is not sufficient to stop or reduce the latent inflammatory and fibrotic processes that have already started in the kidney regardless of the reflux grade and treatment option. Measuring the urinary levels of TGF-β1, VEGF, and MCP-1 may aid in the development of non-invasive, pathophysiologically relevant approach to diagnosis and monitoring of kidney injury and fibrosis in children with VUR.
探讨转化生长因子-β1（TGF-β1）、血管内皮生长因子（VEGF）和单核细胞趋化蛋白-1（MCP-1）在儿童膀胱输尿管反流（VUR）矫正前后 6 个月的尿液水平，作为潜在的肾脏隐匿性炎症和纤维化生物标志物。
88 例 VUR 患儿（平均年龄 26 个月）分为三组：A 组为 II-III 级 VUR 患儿，行保守治疗；B 组为 III-V 级 VUR 患儿，行 VUR 内镜矫正术；C 组为 III-V 级 VUR 患儿，内镜矫正失败后行输尿管再植术。对照组为 20 例健康儿童。采用 ELISA 法检测生物标志物水平。若可能，进行 Tc-DMSA 闪烁扫描和肾组织学检查。
入院时，所有研究组的 TGF-β1 接近对照组，VEGF 随疾病严重程度增加而增加，C 组的 MCP-1 增加。VUR 矫正后 6 个月，尽管临床和实验室检查有所改善，但所有组的 TGF-β1 和 MCP-1 均较入院时增加，而 VEGF 则较入院时降低；Tc-DMSA 闪烁扫描或肾组织学检查均未发现肾瘢痕改善。
研究结果支持我们的假设，即成功矫正 VUR 不足以阻止或减少肾脏已经开始的隐匿性炎症和纤维化过程，而与反流程度和治疗选择无关。测量尿液中 TGF-β1、VEGF 和 MCP-1 的水平可能有助于开发非侵入性、病理生理学相关的方法，用于诊断和监测 VUR 儿童的肾脏损伤和纤维化。
