尿液microRNA-196a与肾脏疾病患者远期预后的关系  

Urinary microRNA-196a as a predictor of long-term outcome in patients with kidney disease

作　　者：张昌明[1] 梁少姗[1] 成水芹[1] 王霞[1] 曾彩虹[1] 郑春霞[1] 刘志红[1] 

机构地区：[1]南京军区南京总医院肾脏科国家肾脏疾病临床医学研究中心全军肾脏病研究所,南京210016

出　　处：《肾脏病与透析肾移植杂志》2016年第6期501-506,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：国家重点研发计划项目(2016YFC0904100);国家科技支撑计划课题(2015BAI12B05);第一批国家临床重点专科项目(2014ZDZK001);江苏省创新能力建设专项(BM2015004);国家自然科学基金(81570644);南京军区南京总医院院管课题(2014003)

摘　　要：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 the association between urinary microRNA-196a（ miR-196a） and long-term outcome in patients with focal segmental glomerulosclerosis（ FSGS）. Methodology： Urinary and plasma miR-196 a were tested in patients with active FSGS（ FSGS-A）,FSGS in complete remission（ FSGS-CR） and normal controls（ NC）. 231 FSGS patients were then enrolled at the time of renal biopsy and urinary miR-196 a levels were measured by qRT-PCR. The relationship between urinary miR-196 a and long-term outcome of FSGS was analyzed. Results： Urinary miR-196 a levels were significantly increased in FSGS-A patients as compared with FSGS-CR patients and NCs（ P〈0. 001）. However,plasma miR-196 a levels showed no difference among the three groups,suggesting that the change of urinary miR-196 a was mainly kidney derived. Of the 231 patients,43 patients developed end-stage renal disease（ ESRD） during the follow-up period. Urinary miR-196 a levels were significantly higher in patients who progressed to ESRD than those not progressed to ESRD（ P = 0. 025）. Urinary miR-196 a was associated with proteinuria,e GFR,and interstitial fibrosis. Patients with higher urinary miR-196 a levels had a higher cumulative incidence of ESRD. Risk persisted after adjusting for age, sex,proteinuria,and eG FR. Conclusion： Urinary miR-196 a is an independent risk factor of ESRD, facilitating early identification of those who will subsequently develop ESRD.

关 键 词：局灶节段性肾小球硬化 尿液 microRNA-196a 远期预后 

分 类 号：R692[医药卫生—泌尿科学]