伴系膜细胞增生特发性膜性肾病中医证候、临床病理特点及预后分析

发布时间：2018-03-17 08:00

  本文选题：特发性膜性肾病　切入点：系膜细胞增生　出处：《北京中医药大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景膜性肾病(Membranous nephropathy,MN)是以肾小球基底膜(GBM)上皮细胞下免复合物沉积伴GBM弥漫增厚为特征的一组疾病,病因未明者称为特发性膜性肾病(idiopathic membranous nephropathy,IMN),是成人肾病综合征常见的病理类型之一。本病病因不明,发病机制复杂,预后呈现很大的个体差异。目前研究认为约1/3的IMN患者可自发缓解,1/3患者发生蛋白尿波动,其余患者则进展至终末期肾病(End Stage Renal Disease,ESRD)或死于相关并发症。相关文献记载典型膜性肾病的病理改变主要在肾小球的基底膜,很少累及系膜区,但临床上IMN伴系膜细胞增生者不在少数,对该类型患者临床表现、病理特征及预后特点的相关研究尚少。虽然中医对本病的认识较完善,根据其临床大量蛋白尿、水肿的特点,归为"尿浊"、"水肿"等范畴,并从宏观和微观角度进行辨证论治,但是IMN伴系膜细胞增生这一病理特征与中医证候相关性研究尚缺乏。因此,本研究拟探讨伴有系膜细胞增生特发性膜性肾病中医证候、临床病理特点,进一步评估此类型IMN预后情况,以期进一步明确系膜细胞增生这一病理改变与中医证候、临床病理及预后的相关性。目的初步探讨伴系膜细胞增生的特发性膜性肾病(IMN)中医证候、临床病理特点及其与预后的相关性。方法采用回顾性研究的方法分析符合纳入标准的IMN患者,根据肾活检病理是否伴有系膜细胞增生,将其分为伴系膜细胞增生组(A组)和不伴系膜细胞增生组(B组);比较两组中医证候、临床病理的差异。对上述患者进行规律随访,对随访中病历资料完整者进一步分析比较,比较两组临床指标、治疗方案、缓解情况及肾脏生存率的差异。结果1.中医症状分布伴系膜细胞增生组首发症状为水肿121例(占87.1%)、泡沫尿120例(占86.3%)、乏力95例(占68.3%)、腰部不适90例(占64.7%)、腹胀60例(占43.1%)、失眠58例(占41.7%)、心慌气短55例(占39.5%);不伴系膜细胞增生组首发症状为乏力95例(占73.75%)、水肿89例(占72.99%)、腰部不适76例(占62.3%)、泡沫尿48例(占39.3%)、心慌气短42例(占34.4%)、失眠40例(占32.75%)、腹胀38例(占31.1%),伴系膜细胞增生组在水肿、泡沫尿的比例明显高于不伴系膜细胞增生组,存在统计学差异(P0.05)。2.中医辨证分型伴系膜细胞增生组与不伴系膜细胞增生组均以气阴两虚、血瘀水停证为主,伴系膜细胞增生组气阴两虚、血瘀水停证62例(占44.6%),其次为脾肾气(阳)虚、血瘀水停证50例(占36%),湿热内蕴、血瘀水停证27例(占19.45%);不伴系膜细胞增生组气阴两虚、血淤水停证65例(占53.3%),其次为湿热内蕴、血瘀水停证29例(占23.8%),脾肾气(阳)虚、血瘀水停证28例(占22.95%)。伴系膜细胞增生组在脾肾气(阳)虚、血瘀水停证的比例明显高于不伴系膜细胞增生组,存在统计学差异(P0.05)。3.一般资料性别:261例患者中,男性141例(占54%),女性120例(占46%)。其中伴系膜细胞增生组男性67例(占48.2%),女性72例(占51.8%),与不伴系膜细胞增生组在性别上有统计学差异(P0.05),伴系膜细胞增生组女性更多见。病程:伴系膜细胞增生组与不伴系膜细胞增生组病程分别为5.0(2.0,12.0)vs4.0(2.0,8.0)月,2组间无统计学差异(P0.05)。肾穿刺年龄:伴系膜细胞增生组与不伴系膜细胞增生组肾穿刺年龄分别为49.28士13.38vs51.54±13.48 岁,2 组间无统计学差异(P0.05)。4.临床特点4.1合并症高血压:伴系膜细胞增生组95例(占68.35%),不伴系膜细胞增生组79例(占64.8%),2组间无统计学意义(P0.05)。冠心病:伴系膜细胞增生组6例(占4.3%),不伴系膜细胞增生组3例(占2.5%),2组间无统计学意义(P0.05)。2型糖尿病:伴系膜细胞增生组12例(占8.6%),不伴系膜细胞增生组19例(占15.8%),2组间无统计学意义(P0.05)。血脂异常:伴系膜细胞增生组101例(占72.7%),不伴系膜细胞增生组99例(占81.1%),2组间无统计学意义(P0.05)。高尿酸血症:伴系膜细胞增生组41例(占29.5%),不伴系膜细胞增生组40例(占32.8%),2组间无统计学意义(P0.05)。动脉硬化:伴系膜细胞增生组3例(占2.2%),不伴系膜细胞增生组3例(占2.5%),2组间无统计学意义(P0.05)。脑血管疾病:伴系膜细胞增生组10例(占7.2%),不伴系膜细胞增生组4例(占3.3%),2组间无统计学意义(P0.05)。4.2实验室指标血浆白蛋白(Alb):伴系膜细胞增生组与不伴系膜细胞增生组为[25.93±6.88vs24.32±6.33]g/L,不伴系膜细胞增生组Alb偏低,2组间无统计学意义(P0.05)。血肌酐(Scr):伴系膜细胞增生组与不伴系膜细胞增生组为[67(55,80)vs70(63,83)]umol/L,不伴系膜细胞增生组Scr偏高,2组间有统计学意义(P0.05)。血脂:伴系膜细胞增生组与不伴系膜细胞增生组血浆甘油三酯(TG)水平为[2.1(1.52,3.04)vs2.4(1.65,3.43)]mmol/L,血浆胆固醇(CH0)水平为[7.0(5.76,8.29)vs7.7(6.54,9.57)]mmol/L,血浆低密度脂蛋白(LDL)水平为[4.25±1.43vs4.86±1.61]mmmol/L。伴系膜细胞增生组血CH0、血LDL水平偏低,2组间有统计学意义(P0.05)。24小时尿蛋白定量(24h-UTP):伴系膜细胞增生组与不伴系膜细胞增生组为[3008(1904,4590)vs3179(2522,4914)]mg/24h,2 组间无统计学差异(P0.05)。尿检红细胞计数≥3/HP:伴系膜细胞增生组与不伴系膜细胞增生组比例为54.7%vs45.9%,2组间无统计学差异(P0.05)。估算肾小球率过滤(eGFR):伴系膜细胞增生组与不伴系膜细胞增生组eGFR值为[104(88.35,120.95)vs96(75.59,116.67)]ml/min/1.73m2,伴系膜细胞增生组 eGFR 相对偏高,2组间有统计学意义(P0.05)。5.肾脏病理资料肾脏病理分期:伴系膜细胞增生组与不伴系膜细胞增生组肾脏病理分期均集中在Ⅰ期、Ⅱ期,两组分别为Ⅰ期膜性肾病[42.4%vs48.4%],Ⅰ-Ⅱ期膜性肾病[21.6%vs14.8%],Ⅱ期膜性肾病[26.6%vs27.9%],Ⅱ-Ⅲ期膜性肾病[8.6%vs8.2%],Ⅲ期膜性肾病[0.7%%vs0.8%],均无ⅣV期膜性肾病,2组间均无统计学意义(P0.05)。肾小球病变:伴系膜细胞增生组节段性硬化8例(占5.7%、球性硬化例50(36%)、新月体14例(10.22%),与不伴系膜细胞增生组比较,均无统计学意义(P0.05)。肾小管病变:伴系膜细胞增生组均见肾小管上皮空泡及颗粒变性,102例(占73.4%)见灶状萎缩。与不伴系膜细胞增生组比较,均无统计学意义(P0.05)。肾间质病变:伴系膜细胞增生组肾间质水肿4例(占2.9%),肾间质炎性细胞浸润98例(占70.5%),间质纤维化103例(占74.1%),与不伴系膜细胞增生组比较,2组间无统计学意义(P0.05)。肾小动脉病变:伴系膜细胞增生组小动脉硬化119例(占85.6%),与不伴系膜细胞增生组比较,2组间无统计学差异(P0.05)。肾组织免疫荧光:伴系膜细胞增生组除见免疫球蛋白IgG、补体C3沉积外,还可见低强度的免疫球蛋白IgA、IgM沉积。其中伴IgA沉积28例(占20.1%),IgM沉积47例(占33.8%),2组间有统计学意义(P0.05)。6.随访情况3年缓解率:伴系膜细胞增生组与不伴系膜细胞增生组3年肾脏缓解情况为[56例(占59.6%)vs33例(占42.3%)],2组间有统计学意义(P0.05)。肾脏累计生存率:采用Kaplan-Meier·法评价两组患者肾脏累计生存率,2组间无统计学意义(x2=1.248,P=0.264)。肾脏累计缓解率:采用Kaplan-Meier法评价两组患者首次达到完全缓解的情况,2组间累计缓解率无统计学意义(x2=1.965,P=0.161)。影响肾脏缓解的危险因素:年龄50岁是影响IMN临床缓解的独立危险因素,免疫抑制剂的应用是肾脏达到缓解的有利因素,系膜细胞增生与IMN预后无明显相关。结论伴系膜细胞增生IMN以水肿,泡沫尿为突出症状,主要中医证型为脾肾气(阳)虚、血瘀水停证,女性发病居多,肾功能损害较轻。肾脏病理免疫荧光提示,除IgG,补体C3沉积外,还伴有低强度IgA、IgM沉积。系膜细胞增生与IMN预后无明显相关。
[Abstract]:The background of membranous nephropathy (Membranous nephropathy, MN) in the glomerular basement membrane (GBM) is a group of diseases of epithelial cells under free complex deposition with GBM diffuse thickening of unknown etiology, called idiopathic membranous nephropathy (idiopathic membranous, nephropathy, IMN), is one of the common adult nephrotic syndrome pathology this type of disease of unknown etiology, complicated pathogenesis, prognosis showed great individual differences. Current studies suggest that about 1/3 IMN patients with spontaneous remission, 1/3 patients with proteinuria fluctuations, the remaining patients progress to end-stage kidney disease (End Stage Renal Disease, ESRD) or died of related complications. The pathological changes of related literature typical membranous nephropathy mainly in the glomerular basement membrane, rarely involving mesangial area, but clinically IMN patients with mesangial cell proliferation were few, the clinical manifestations of this type of patients, pathological characteristics and prognosis characteristics The related research is less. Although the Chinese understanding of the disease better, according to the clinical proteinuria, edema, classified as "turbid urine", "edema" and other areas, and differentiation from the perspective of macro and micro, but IMN with the proliferation of mesangial cells of the pathological characteristics and Study on correlation between TCM syndromes is still lacking. Therefore, this study aims to investigate the proliferation of mesangial cells with idiopathic nephrotic syndrome of traditional Chinese medicine membrane, clinical and pathological features, further evaluation of this type of IMN prognosis, in order to further clarify the proliferation of mesangial cells of the pathological change and correlation between TCM syndromes, clinical pathology and prognosis. Objective to investigate idiopathic membranous nephropathy and mesangial cell proliferation (IMN) TCM syndrome, clinical pathological features and their correlation with prognosis. Methods a retrospective study of IMN patients met the inclusion criteria, based on renal biopsy is 鍚︿即鏈夌郴鑶滅粏鑳炲�炵敚�

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