伴系膜細(xì)胞增生特發(fā)性膜性腎病中醫(yī)證候、臨床病理特點及預(yù)后分析
發(fā)布時間:2018-03-17 08:00
本文選題:特發(fā)性膜性腎病 切入點:系膜細(xì)胞增生 出處:《北京中醫(yī)藥大學(xué)》2017年碩士論文 論文類型:學(xué)位論文
【摘要】:背景膜性腎病(Membranous nephropathy,MN)是以腎小球基底膜(GBM)上皮細(xì)胞下免復(fù)合物沉積伴GBM彌漫增厚為特征的一組疾病,病因未明者稱為特發(fā)性膜性腎病(idiopathic membranous nephropathy,IMN),是成人腎病綜合征常見的病理類型之一。本病病因不明,發(fā)病機制復(fù)雜,預(yù)后呈現(xiàn)很大的個體差異。目前研究認(rèn)為約1/3的IMN患者可自發(fā)緩解,1/3患者發(fā)生蛋白尿波動,其余患者則進展至終末期腎病(End Stage Renal Disease,ESRD)或死于相關(guān)并發(fā)癥。相關(guān)文獻記載典型膜性腎病的病理改變主要在腎小球的基底膜,很少累及系膜區(qū),但臨床上IMN伴系膜細(xì)胞增生者不在少數(shù),對該類型患者臨床表現(xiàn)、病理特征及預(yù)后特點的相關(guān)研究尚少。雖然中醫(yī)對本病的認(rèn)識較完善,根據(jù)其臨床大量蛋白尿、水腫的特點,歸為"尿濁"、"水腫"等范疇,并從宏觀和微觀角度進行辨證論治,但是IMN伴系膜細(xì)胞增生這一病理特征與中醫(yī)證候相關(guān)性研究尚缺乏。因此,本研究擬探討伴有系膜細(xì)胞增生特發(fā)性膜性腎病中醫(yī)證候、臨床病理特點,進一步評估此類型IMN預(yù)后情況,以期進一步明確系膜細(xì)胞增生這一病理改變與中醫(yī)證候、臨床病理及預(yù)后的相關(guān)性。目的初步探討伴系膜細(xì)胞增生的特發(fā)性膜性腎病(IMN)中醫(yī)證候、臨床病理特點及其與預(yù)后的相關(guān)性。方法采用回顧性研究的方法分析符合納入標(biāo)準(zhǔn)的IMN患者,根據(jù)腎活檢病理是否伴有系膜細(xì)胞增生,將其分為伴系膜細(xì)胞增生組(A組)和不伴系膜細(xì)胞增生組(B組);比較兩組中醫(yī)證候、臨床病理的差異。對上述患者進行規(guī)律隨訪,對隨訪中病歷資料完整者進一步分析比較,比較兩組臨床指標(biāo)、治療方案、緩解情況及腎臟生存率的差異。結(jié)果1.中醫(yī)癥狀分布伴系膜細(xì)胞增生組首發(fā)癥狀為水腫121例(占87.1%)、泡沫尿120例(占86.3%)、乏力95例(占68.3%)、腰部不適90例(占64.7%)、腹脹60例(占43.1%)、失眠58例(占41.7%)、心慌氣短55例(占39.5%);不伴系膜細(xì)胞增生組首發(fā)癥狀為乏力95例(占73.75%)、水腫89例(占72.99%)、腰部不適76例(占62.3%)、泡沫尿48例(占39.3%)、心慌氣短42例(占34.4%)、失眠40例(占32.75%)、腹脹38例(占31.1%),伴系膜細(xì)胞增生組在水腫、泡沫尿的比例明顯高于不伴系膜細(xì)胞增生組,存在統(tǒng)計學(xué)差異(P0.05)。2.中醫(yī)辨證分型伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組均以氣陰兩虛、血瘀水停證為主,伴系膜細(xì)胞增生組氣陰兩虛、血瘀水停證62例(占44.6%),其次為脾腎氣(陽)虛、血瘀水停證50例(占36%),濕熱內(nèi)蘊、血瘀水停證27例(占19.45%);不伴系膜細(xì)胞增生組氣陰兩虛、血淤水停證65例(占53.3%),其次為濕熱內(nèi)蘊、血瘀水停證29例(占23.8%),脾腎氣(陽)虛、血瘀水停證28例(占22.95%)。伴系膜細(xì)胞增生組在脾腎氣(陽)虛、血瘀水停證的比例明顯高于不伴系膜細(xì)胞增生組,存在統(tǒng)計學(xué)差異(P0.05)。3.一般資料性別:261例患者中,男性141例(占54%),女性120例(占46%)。其中伴系膜細(xì)胞增生組男性67例(占48.2%),女性72例(占51.8%),與不伴系膜細(xì)胞增生組在性別上有統(tǒng)計學(xué)差異(P0.05),伴系膜細(xì)胞增生組女性更多見。病程:伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組病程分別為5.0(2.0,12.0)vs4.0(2.0,8.0)月,2組間無統(tǒng)計學(xué)差異(P0.05)。腎穿刺年齡:伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組腎穿刺年齡分別為49.28士13.38vs51.54±13.48 歲,2 組間無統(tǒng)計學(xué)差異(P0.05)。4.臨床特點4.1合并癥高血壓:伴系膜細(xì)胞增生組95例(占68.35%),不伴系膜細(xì)胞增生組79例(占64.8%),2組間無統(tǒng)計學(xué)意義(P0.05)。冠心病:伴系膜細(xì)胞增生組6例(占4.3%),不伴系膜細(xì)胞增生組3例(占2.5%),2組間無統(tǒng)計學(xué)意義(P0.05)。2型糖尿病:伴系膜細(xì)胞增生組12例(占8.6%),不伴系膜細(xì)胞增生組19例(占15.8%),2組間無統(tǒng)計學(xué)意義(P0.05)。血脂異常:伴系膜細(xì)胞增生組101例(占72.7%),不伴系膜細(xì)胞增生組99例(占81.1%),2組間無統(tǒng)計學(xué)意義(P0.05)。高尿酸血癥:伴系膜細(xì)胞增生組41例(占29.5%),不伴系膜細(xì)胞增生組40例(占32.8%),2組間無統(tǒng)計學(xué)意義(P0.05)。動脈硬化:伴系膜細(xì)胞增生組3例(占2.2%),不伴系膜細(xì)胞增生組3例(占2.5%),2組間無統(tǒng)計學(xué)意義(P0.05)。腦血管疾病:伴系膜細(xì)胞增生組10例(占7.2%),不伴系膜細(xì)胞增生組4例(占3.3%),2組間無統(tǒng)計學(xué)意義(P0.05)。4.2實驗室指標(biāo)血漿白蛋白(Alb):伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組為[25.93±6.88vs24.32±6.33]g/L,不伴系膜細(xì)胞增生組Alb偏低,2組間無統(tǒng)計學(xué)意義(P0.05)。血肌酐(Scr):伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組為[67(55,80)vs70(63,83)]umol/L,不伴系膜細(xì)胞增生組Scr偏高,2組間有統(tǒng)計學(xué)意義(P0.05)。血脂:伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組血漿甘油三酯(TG)水平為[2.1(1.52,3.04)vs2.4(1.65,3.43)]mmol/L,血漿膽固醇(CH0)水平為[7.0(5.76,8.29)vs7.7(6.54,9.57)]mmol/L,血漿低密度脂蛋白(LDL)水平為[4.25±1.43vs4.86±1.61]mmmol/L。伴系膜細(xì)胞增生組血CH0、血LDL水平偏低,2組間有統(tǒng)計學(xué)意義(P0.05)。24小時尿蛋白定量(24h-UTP):伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組為[3008(1904,4590)vs3179(2522,4914)]mg/24h,2 組間無統(tǒng)計學(xué)差異(P0.05)。尿檢紅細(xì)胞計數(shù)≥3/HP:伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組比例為54.7%vs45.9%,2組間無統(tǒng)計學(xué)差異(P0.05)。估算腎小球率過濾(eGFR):伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組eGFR值為[104(88.35,120.95)vs96(75.59,116.67)]ml/min/1.73m2,伴系膜細(xì)胞增生組 eGFR 相對偏高,2組間有統(tǒng)計學(xué)意義(P0.05)。5.腎臟病理資料腎臟病理分期:伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組腎臟病理分期均集中在Ⅰ期、Ⅱ期,兩組分別為Ⅰ期膜性腎病[42.4%vs48.4%],Ⅰ-Ⅱ期膜性腎病[21.6%vs14.8%],Ⅱ期膜性腎病[26.6%vs27.9%],Ⅱ-Ⅲ期膜性腎病[8.6%vs8.2%],Ⅲ期膜性腎病[0.7%%vs0.8%],均無ⅣV期膜性腎病,2組間均無統(tǒng)計學(xué)意義(P0.05)。腎小球病變:伴系膜細(xì)胞增生組節(jié)段性硬化8例(占5.7%、球性硬化例50(36%)、新月體14例(10.22%),與不伴系膜細(xì)胞增生組比較,均無統(tǒng)計學(xué)意義(P0.05)。腎小管病變:伴系膜細(xì)胞增生組均見腎小管上皮空泡及顆粒變性,102例(占73.4%)見灶狀萎縮。與不伴系膜細(xì)胞增生組比較,均無統(tǒng)計學(xué)意義(P0.05)。腎間質(zhì)病變:伴系膜細(xì)胞增生組腎間質(zhì)水腫4例(占2.9%),腎間質(zhì)炎性細(xì)胞浸潤98例(占70.5%),間質(zhì)纖維化103例(占74.1%),與不伴系膜細(xì)胞增生組比較,2組間無統(tǒng)計學(xué)意義(P0.05)。腎小動脈病變:伴系膜細(xì)胞增生組小動脈硬化119例(占85.6%),與不伴系膜細(xì)胞增生組比較,2組間無統(tǒng)計學(xué)差異(P0.05)。腎組織免疫熒光:伴系膜細(xì)胞增生組除見免疫球蛋白IgG、補體C3沉積外,還可見低強度的免疫球蛋白IgA、IgM沉積。其中伴IgA沉積28例(占20.1%),IgM沉積47例(占33.8%),2組間有統(tǒng)計學(xué)意義(P0.05)。6.隨訪情況3年緩解率:伴系膜細(xì)胞增生組與不伴系膜細(xì)胞增生組3年腎臟緩解情況為[56例(占59.6%)vs33例(占42.3%)],2組間有統(tǒng)計學(xué)意義(P0.05)。腎臟累計生存率:采用Kaplan-Meier·法評價兩組患者腎臟累計生存率,2組間無統(tǒng)計學(xué)意義(x2=1.248,P=0.264)。腎臟累計緩解率:采用Kaplan-Meier法評價兩組患者首次達到完全緩解的情況,2組間累計緩解率無統(tǒng)計學(xué)意義(x2=1.965,P=0.161)。影響腎臟緩解的危險因素:年齡50歲是影響IMN臨床緩解的獨立危險因素,免疫抑制劑的應(yīng)用是腎臟達到緩解的有利因素,系膜細(xì)胞增生與IMN預(yù)后無明顯相關(guān)。結(jié)論伴系膜細(xì)胞增生IMN以水腫,泡沫尿為突出癥狀,主要中醫(yī)證型為脾腎氣(陽)虛、血瘀水停證,女性發(fā)病居多,腎功能損害較輕。腎臟病理免疫熒光提示,除IgG,補體C3沉積外,還伴有低強度IgA、IgM沉積。系膜細(xì)胞增生與IMN預(yù)后無明顯相關(guān)。
[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?yōu)澧炵敚?
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