糖尿病肾病病理特点

糖尿病肾脏疾病定义DKD是指由糖尿病引起的慢性肾病，主要包括肾小球滤过率(GFR)低于60ml/min/1.73m2或尿白蛋白／肌酐比值(ACR)高于30mg／g持续超过3个月糖尿病性肾小球肾病(diabeticglomerulopathy)专指经肾脏活检证实的由糖尿病引起的肾小球病变糖化终末产物肾小球高滤过肥厚氧化应激PKC↑多元醇通路活性↑TGF-βAng-ⅡGH/IGF-ⅠNO白介素高血压、高血脂、吸烟遗传糖尿病肾病的发病机制高血糖糖尿病肾病AdaptedfromBreyerJAetal.AmJKidDis1992;20(6):535.时间(年)052030糖尿病开始蛋白尿开始终末期肾病结构改变(肾小球基底膜增多且系膜扩展)高血压糖尿病肾病的自然进程明显肾病(Scr,升高GFR降低)初期肾病(高滤过,微白蛋白尿,血压升高)临床前的肾病糖尿病肾脏病变诊断标准在大部分糖尿病患者中，出现以下任何一条者考虑其肾脏损伤是由糖尿病引起的(1)大量白蛋白尿(2)糖尿病视网膜病变伴微量白蛋白尿?(3)在1O年以上糖尿病病程的l型糖尿病中出现微量白蛋白尿美国肾脏基金会肾脏病预后质量倡议(NKF—K／DOQI)指南标准糖尿病合并肾脏损伤不一定是糖尿病肾病(1)无糖尿病视网膜病变(2)GFR较低或迅速下降(3)蛋白尿急剧增多或有肾病综合征(4)顽固性高血压(5)尿沉渣活动表现（血尿、白细胞尿、管型尿）(6)其他系统性疾病的症状或体征(7)ACEI或ARB开始治疗后2～3个月内肾小球滤过率下降超过30％糖尿病出现以下情况考虑活检糖尿病病程较短既往有肾脏病病史肾损害早于糖尿病，糖尿病与肾损害同时出现，或糖尿病早期出现肾损害血尿明显有肾损害而不伴有其他糖尿病微血管糖尿病肾脏疾病的病理--肾脏大体标本1.弥漫性肾小球硬化：肾小球系膜基质增宽肾小球基底膜弥漫增厚此型表现并非DN特有光学显微镜检查糖尿病肾病的基本病理变化——呈现两种病理类型Slide3—Normalglomerulus:Hematoxylinandeosinstainofanormalglomerulussectionedthroughthevascularpole.Notethewide-opencapillaryluminaandthelargepercentageofthecross-sectionalareaoftheglomerulusdevotedtothecapillarycirculation.Themesangialcellularityandmatrixarenormal.Slide1—Normalglomerulus:Schematizeddrawingofanormalglomerulusshowingepithelialcellsingreen,endothelialcellsinyellowandmesangialcellsinred.Notethattheglomerularbasementmembranes(inblack)donotcompletelysurroundcapillaryloops,andthatendothelialcellsareindirectcontactwithmesangialmatrix(blue)atthemesangialpolesofcapillaries.糖尿病肾病的特征性病理改变BurtonDRose，MD2000Slide165—Diabeticnephropathy:ThisschematizeddrawingshowsthemarkedlythickenedlaminadensaoftheGBMandincreasedmesangialmatrixmaterialwhicharethesinequanonofdiabeticrenaldisease.Thesubsequentslides(166-202)demonstratethespectrumofdiabeticrenaldisease(startingwithareviewofnormalglomerularhistology),andillustratedistinguishingpointsbetweenothertypesofglomerulopathieswhichmaymimicdiabeticnephropathy.糖尿病肾病：肾小球基底膜增厚伴系膜基质扩张Slide167—Moderatediffusediabeticglomerulosclerosisinaninsulin-dependentdiabetic(IDDM)patientwith16years’duration.Notethewideningoftheglomerularmesangium,therestrictionoftheglomerularcapillarycirculation,thethickeningoftheglomerularbasementmembranecomparedtoslide1,andthehyalinosisofthearteriolarwallatthevascularpole(PAS).弥漫性轻度糖尿病肾小球硬化：系膜区基质扩张，GBM增厚，毛细血管腔受压，血管极小动脉壁增厚Slide168—Markeddiffusediabeticglomerulosclerosis.Thereisextremeexpansionofthemesangiumwithbothmatrixandcellularmaterial.Thecapillarylumenalcirculationismarkedlyconstricted(PAS).Whereasthepatientinslide2hadnormalrenalfunction,thispatienthadovertnephropathywithproteinuria,hypertension,anda50%reductioninGFR.弥漫、严重糖尿病肾小球硬化：系膜区基质及细胞显著增加，毛细血管腔严重受压；该患者肾小球滤过率下降50%，伴显著蛋白尿、严重高血压糖尿病肾病的病理变化（五）2.结节性肾小球硬化：肾小球系膜基质增宽及分裂，并且出现Kimmelstiel-Wilson结节肾小球基底膜弥漫增厚，球囊滴（透明变性），纤维蛋白帽（透明变性和脂质沉着），毛细血管襻微血管瘤，出、入球小动脉透明变性及动脉硬化此型为DN特异光学显微镜检查糖尿病肾病的病理变化Slide171—Nodulardiabeticglomerulosclerosis(Kimmelstiel-Wilsonlesions)inapatientwithovertdiabeticnephropathyandproteinuria,hypertension,andreducedGFR.Notethepalisadingofmesangialnucleiaroundtheperipheryofthenoduleandthefibrillarnatureofthenodularmatrixmaterial.Notealsotherestrictionofglomerularcapillarylumenalspace(PAS).结节性肾小球硬化（K-W结节）：伴蛋白尿、高血压及肾小球滤过率下降糖尿病肾病的其他病理变化Slide178—AcapsulardropconsistingofhyalinePASpositivematerialdepositedontheparietalsurfaceofBowman’smembrane(9o’clock).帽状滴：透明PAS阳性物质沉积于肾小球囊之内侧壁Slide179—Formationofacapsulardropbyadhesionofglomerularcapillaryloopscontainingsubendothelialhyaline(theso-called“exudativelesion”)toBowman’scapsule(9o’clockand11o’clock).Itislikelythattheglomerularcapillaryloopsretract,depositingthehyalinematerialalongtheBowman’scapsularwall.帽状滴之形成：肾小球毛细血管袢渗出性物质（内皮细胞下透明样物质）附着与肾小球囊之内侧壁，然后肾小球收缩。小动脉透明样变性（右图）Slide174—Earlyglomerulararteriolarhyalinosisinanafferentarteriole.Notethesmooth,waxy,homogenousPASpositivematerialinthesubendothelialspace.ThisIDDMpatienthadnormalrenalfunction.入球小动脉透明样变性早期改变：内皮细胞下非细胞均质成份沉积，肾功能尚正常Slide176—Arteriolarhyalinosisinbothafferent(lowerleftside)andefferent(lowerrightside)glomerulararterioles(PAS).NotethediffuseandnodulardiabeticglomerulosclerosisinthisIDDMpatientwithearlyovertnephropathy.入球小动脉与出球小动脉壁透明样变，弥漫性糖尿病结节性肾小球硬化：１型糖尿病引起的临床糖尿病肾病之早期Slide175—Advancedarteriolarhyalinosiswithvirtualcompletereplacementofthevesselwallbyhyalinewaxymaterial(PAS).蜡样物质填充于小动脉壁，引起血管腔几乎完全闭塞Slide200—ThisandthesubsequenttwoslidesillustratetheatypicallesionscommonlyseeninmicroalbuminuricNIDDMpatients.Someofthesepatients,asillustratedinthisPASslide,haveestablishedarteriolarhyalinosislesionswithlittleornoglomerularortubulointerstitialinjury.2型糖尿病伴微量白蛋白尿：不典型肾脏改变—小动脉显著透明样变性，而肾小球以及肾间质改变不明显Slide181—Mildexpansionoftheinterstitialspaceandtubularbasementmembranethickeningwithouttubularatrophy(PAS).ThisIDDMpatienthadnormalrenalfunction.Thismilddegreeofinterstitialexpansioniscommonindiabeticpatients,eventhosewhoseglomerularandvasculardiseasedonotprogress.间质间隙轻度扩张，伴肾小管基膜增厚，肾小管不萎缩：1型糖尿病患者，肾功能正常。一些不伴肾小球或肾小管损伤的糖尿病患者也可发生这种小管间质改变Slide182—Moreadvancedtubularinterstitialdiseasewithtubularatrophyandinterstitialfibrosisindicatedbythegreencoloronthetrichromestaining.ThisIDDMpatienthadmilddiffusedia