Bobkova I N, Chebotareva N V, Kozlovskaia L V, Varshavskiĭ V A, Golitsyna E P
Ter Arkh. 2006;78(5):9-14.
To measure urine and renal tissue levels of profibrogenic mediators (monocytic chemotaxic protein-1-MCP-1 and transforming growth factor beta1 - TGF-b1) in patients with chronic glomerulonephritis (CGN); to specify significance of these mediators for assessment of inflammation and fibrosis in the kidney and as prognosis criteria. ELISA, immunohistochemical tests, morphometry were used to study urine excretion of MCP-1 and TGF-b1, expression of TGF-b1 in renal tissue, interstitial area, respectively, in 63 patients with active proteinuric CGN.
Patients with active proteinuric forms of CGN have higher urine excretion of MCP-1 and TGF-b1 than healthy controls. Urine excretion of MCP-1 in patients with nephrotic syndrome was significantly higher than in patients with moderate urinary syndrome. The highest MCP-1 urine excretion was observed in patients with persistent renal failure. Urine excretion of TGF-b1 depended on the level of creatinemia being the highest in marked proteinuria and stable renal dysfunction. Intensive urine excretion of TGF-b1 occurred in CGN patients with expression of this cytokine in renal interstitium. This confirms its local-renal origin. A correlation was found between urine values of MCP-1, TGF-b1 and severity of tubulo-interstitial fibrosis (TIF). High informative value (sensitivity and specificity) of urine MCP-1 and TGF-b1 are for the first time shown as markers of interstitial fibrosis. They are also important for making prognosis of CGN.
It is shown that MCP-1 and TGF-b1 are essential for remodeling of tubulointerstitium. The urinary parameters mark TIF and can be used as criteria of activity and prognosis of CGN.
测定慢性肾小球肾炎(CGN)患者尿液及肾组织中促纤维化介质(单核细胞趋化蛋白-1-MCP-1和转化生长因子β1-TGF-β1)的水平;明确这些介质在评估肾脏炎症和纤维化以及作为预后标准方面的意义。采用酶联免疫吸附测定(ELISA)、免疫组织化学检测、形态计量学方法,分别研究63例活动性蛋白尿性CGN患者尿液中MCP-1和TGF-β1的排泄情况、肾组织中TGF-β1的表达情况以及间质面积。
活动性蛋白尿性CGN患者尿液中MCP-1和TGF-β1的排泄量高于健康对照组。肾病综合征患者尿液中MCP-1的排泄量显著高于中度尿综合征患者。持续性肾衰竭患者尿液中MCP-1的排泄量最高。TGF-β1的尿液排泄量取决于肌酐血症水平,在显著蛋白尿和稳定的肾功能不全患者中最高。TGF-β1在肾间质中表达的CGN患者出现大量尿液排泄。这证实了其肾脏局部来源。发现MCP-1、TGF-β1的尿液值与肾小管间质纤维化(TIF)的严重程度之间存在相关性。首次显示尿液MCP-1和TGF-β1作为间质纤维化标志物具有高信息价值(敏感性和特异性)。它们对CGN的预后判断也很重要。
结果表明,MCP-1和TGF-β1对肾小管间质重塑至关重要。尿液参数可标记TIF,并可作为CGN活动度和预后的标准。