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目的:探讨尿液microRNA-196a(miR-196a)能否作为预测局灶节段性肾小球硬化(FSGS)远期预后的生物标志物。方法:收集FSGS患者和正常对照的尿液和血浆标本,分析尿液和血浆miR-196a水平与FSGS活动性的关系。入选231例经肾活检确诊的FSGS,qRT-PCR方法检测尿液miR-196a水平,评估尿液miR-196a对FSGS预后的预测价值。结果:尿液miR-196a水平在活动性FSGS患者组显著高于肾脏疾病完全缓解组和正常对照组(P<0.001),血浆miR-196a水平在三组之间无明显差异,表明尿液miR-196a是一种主要来源于肾脏的生物标志物。231例随访患者中,43例进展为终末期肾病(ESRD)。发生ESRD的患者尿液miR-196a水平显著高于未发生ESRD的患者(P=0.025)。尿液miR-196a水平与蛋白尿和估算的肾小球滤过率(e GFR)相关,与肾间质纤维化评分存在相关性。随着尿液miR-196a水平增加,患者发生ESRD的风险增加。校正年龄、性别、蛋白尿、e GFR后尿液miR-196a升高仍是患者进展至ESRD的独立危险因素。结论:尿液miR-196a是FSGS患者发生ESRD的独立危险因素,可能成为预测FSGS远期预后的新型生物标志物。
Objective: To investigate whether urine microRNA-196a (miR-196a) can be used as a biomarker to predict the long-term prognosis of focal segmental glomerulosclerosis (FSGS). Methods: Urine and plasma samples from FSGS patients and normal controls were collected to analyze the relationship between urine and plasma levels of miR-196a and FSGS activity. 231 cases of FSGS diagnosed by renal biopsy were selected and the levels of miR-196a in urine were detected by qRT-PCR to evaluate the predictive value of urine miR-196a in the prognosis of FSGS. Results: The level of miR-196a in urine of patients with active FSGS was significantly higher than that of patients with complete remission and normal control (P <0.001), and there was no significant difference in plasma levels of miR-196a between the three groups, indicating that urine miR -196a is a biomarker that is primarily derived from the kidneys. Of 231 patients who were followed up, 43 progressed to end-stage renal disease (ESRD). Urine levels of miR-196a were significantly higher in patients with ESRD than in patients without ESRD (P = .025). Urine levels of miR-196a were associated with proteinuria and estimated glomerular filtration rate (e GFR) and correlated with renal interstitial fibrosis scores. As urine miR-196a levels increase, patients have an increased risk of ESRD. Correction of urine miR-196a after age, gender, proteinuria, and eGFR remained independent risk factors for progression to ESRD. Conclusion: Urine miR-196a is an independent risk factor for ESRD in patients with FSGS, which may be a new biomarker to predict long-term prognosis of FSGS.