內(nèi)科學(xué)教學(xué)課件：腎小球腎炎

腎小球腎炎

GlomerulonephritisPekingUniversityTheThirdHospitalRenalDivision內(nèi)容正常腎臟結(jié)構(gòu)與功能原發(fā)性腎小球疾病概述腎病綜合征（NS）急性感染后腎小球腎炎（APGN）急進(jìn)性腎小球腎炎（RPGN）IgA腎病

（IgAN）概述一組疾病病變部位在腎小球病因、發(fā)病機(jī)制、臨床表現(xiàn)、病理、治療、預(yù)后相似或相異PekingUniversityTheThirdHospitalRenalDivision腎小球疾病分類按病因按發(fā)病機(jī)制按臨床表現(xiàn)按病理PekingUniversityTheThirdHospitalRenalDivision腎小球疾病的病因分類原發(fā)性原因暫時(shí)不明繼發(fā)性全身疾病的一部分SLE過(guò)敏性紫癜糖尿病腫瘤遺傳性PekingUniversityTheThirdHospitalRenalDivision腎小球疾病的發(fā)病機(jī)制及其分類免疫介導(dǎo)體液免疫異常循環(huán)免疫復(fù)合物致病如SLE，IgAN

腎臟原位免疫復(fù)合物如GBM、PLA2R細(xì)胞免疫異常非免疫介導(dǎo)血液動(dòng)力學(xué)異常內(nèi)分泌代謝異常遺傳學(xué)異常PekingUniversityTheThirdHospitalRenalDivision按臨床表現(xiàn)分類腎病綜合征（Nephroticsyndrome）急性腎炎綜合征（Acutenephriticsyndrome）急進(jìn)性腎炎綜合征（

Rapidlyprogressivenephriticsyndrome）慢性腎炎綜合征（Chronicnephriticsyndrome）隱匿型腎小球腎炎（Latentnephriticsyndrome）PekingUniversityTheThirdHospitalRenalDivisionSpectrumofprimary

glomerulardiseasesNephrolDialTransplant(2009)24:870–876腎小球疾病的病理分型

（WHO，1982）輕微病變性腎病（MCN）局灶性節(jié)段性腎小球腎炎（FSGN）彌漫性腎小球腎炎（DiffuseGN）增生性系膜增生性（MsPGN）毛細(xì)血管內(nèi)增生性（ECGN）系膜毛細(xì)血管內(nèi)增生性（MPGN)電子致密物沉積性（DDD）新月體性(CrescenticGN)膜性腎?。∕N）硬化性（SclerosisGN）不易分類的腎小球病PekingUniversityTheThirdHospitalRenalDivision腎小球疾病的診斷及格式病因診斷 臨床診斷病理診斷功能診斷 并發(fā)疾病診斷PekingUniversityTheThirdHospitalRenalDivisionKDIGOguideline2012PekingUniversityTheThirdHospitalRenalDivision病例1患者，女，11歲主因“水腫，少尿，茶色尿1周”來(lái)診。3周前上感，咽痛，發(fā)熱38.3℃，外院用頭孢類抗生素及阿奇霉素治療，體溫恢復(fù)正常1周來(lái)出現(xiàn)顏面及雙下肢水腫，尿色呈濃茶色，尿量顯著減少，約600-700ml/日PekingUniversityTheThirdHospitalRenalDivision病例1查體：T37.0℃，P102次/分，BP160/100mmHg，顏面眼瞼水腫，全身淺表淋巴結(jié)未觸及。雙肺呼吸音清，未聞及干濕羅音，心界不大，HR102次/分，律齊，未聞及雜音。腹軟，肝脾未觸及，移動(dòng)性濁音（-）。雙下肢可凹性水腫。PekingUniversityTheThirdHospitalRenalDivision病例1輔助檢查：

血常規(guī)：Hb115g/L，WBC，Plt正常

尿常規(guī)：蛋白3+，潛血3+，比重1.020，紅細(xì)胞25-30/HP，白細(xì)胞3-5/HP

血生化：ALB35g/L，BUN8.0mmol/L，Cr105μmol/L

免疫：自身抗體（-），免疫球蛋白正常，C30.364PekingUniversityTheThirdHospitalRenalDivision腎活檢PekingUniversityTheThirdHospitalRenalDivision

AcutePost-StreptococcalGlomerulonephritis

急性鏈球菌感染后腎小球腎炎PekingUniversityTheThirdHospitalRenalDivision病因A型溶血性鏈球菌致腎炎菌株呼吸道感染猩紅熱膿皰瘡病毒其他病原體PekingUniversityTheThirdHospitalRenalDivision發(fā)病機(jī)理

鏈球菌致腎炎菌株菌內(nèi)物質(zhì)（ESS)菌株伴隨蛋白（NSAP)陽(yáng)電荷菌體外成分神經(jīng)氨酸酶……？循環(huán)免疫復(fù)合物原位免疫復(fù)合物與GBM交叉抗原性誘發(fā)自體免疫細(xì)胞介導(dǎo)免疫激活補(bǔ)體及各種炎癥介質(zhì)腎小球炎癥病變內(nèi)皮細(xì)胞腫脹，系膜細(xì)胞增生毛細(xì)血管腔閉塞腎小球?yàn)V過(guò)面積↓，GFR↓球管失衡水鈉潴留，血容量擴(kuò)張腎小球基底膜破壞蛋白尿血尿管型尿氮質(zhì)血癥，尿毒癥少尿，無(wú)尿水腫，高血壓，心衰PekingUniversityTheThirdHospitalRenalDivisionPekingUniversityTheThirdHospitalRenalDivision病理

LM：彌漫毛細(xì)血管內(nèi)增生IF：IgG和C3，粗顆粒狀，沿毛細(xì)血管壁及系膜區(qū)沉積EM：上皮下“駝峰樣”電子致密物PekingUniversityTheThirdHospitalRenalDivision臨床表現(xiàn)高發(fā)年齡2-6歲前驅(qū)感染史潛伏期7-21天

急性起病急性腎炎綜合征acutenephriticsyndromePekingUniversityTheThirdHospitalRenalDivisionclinicalmanifestationincidencehematuria100％（30%grosshematuria）edema80-90%hypertension60-80%（50%sever）oliguria10-50%（15%＜200ml/d)generalmalaise，fatigue，lossofappetite，nausea&vomiting

15-50%PekingUniversityTheThirdHospitalRenalDivision兒童（％）老人（％）充血性心力衰竭＜543腎病綜合征4-1020腦病

moreless急性腎衰竭25-4083死亡＜125合并癥PekingUniversityTheThirdHospitalRenalDivision輔助檢查尿常規(guī)：100%血尿，RBCcasts蛋白尿

：輕-中腎功能：一過(guò)性GFR↓其他：ASO↑C3↓(4-8w)CIC+，cryoglobulins+貧血PekingUniversityTheThirdHospitalRenalDivision治療

一般治療臥床休息飲食:低鹽（每日食鹽＜3g）利尿降壓

抗感染透析少尿、急性腎衰竭、高鉀血癥病例2患者，女，40歲主因“血尿1月，水腫，少尿1周”來(lái)診。1月前無(wú)誘因出現(xiàn)洗肉水樣尿，無(wú)血絲、血塊，不伴尿頻、尿急、尿痛，無(wú)發(fā)熱、腰痛。服云南白藥治療，血尿無(wú)好轉(zhuǎn)。1周來(lái)尿量顯著減少，約200ml/日，出現(xiàn)雙下肢水腫、納差。PekingUniversityTheThirdHospitalRenalDivision病例2查體：T37.5℃，P90次/分，BP150/95mmHg，顏面眼瞼水腫，全身淺表淋巴結(jié)未觸及。雙肺呼吸音清，未聞及干濕羅音，心界不大，HR90次/分，律齊，未聞及雜音。腹軟，肝脾未觸及，移動(dòng)性濁音（-）。雙下肢可凹性水腫。PekingUniversityTheThirdHospitalRenalDivision病例2輔助檢查：

血常規(guī)：Hb90g/L，WBC，Plt正常

尿常規(guī)：蛋白3+，潛血3+，比重1.025，RBC滿視野/HP，WBC1-3/HP

血生化：ALB32g/L，BUN28.0mmol/L，Cr568μmol/L

免疫：GBM抗體1:180，ANA(-)，dsDNA(-)，ANCA（-）PekingUniversityTheThirdHospitalRenalDivision腎活檢PekingUniversityTheThirdHospitalRenalDivisionRapidlyprogressiveglomerulonephritis

(RPGN)

急進(jìn)性腎小球腎炎PekingUniversityTheThirdHospitalRenalDivision概述AcuteonsetRapidlyprogressiveAcutenephriticsyndromeRenalfailurewithinafewweekstoafewmonthsPathology–CrescentGNPekingUniversityTheThirdHospitalRenalDivisionPekingUniversityTheThirdHospitalRenalDivisionPekingUniversityTheThirdHospitalRenalDivision1.原發(fā)性RPGNCrescentGN2.繼發(fā)性RPGNSLE,SHP,etcRPGNRPGN分型PekingUniversityTheThirdHospitalRenalDivision

TypeITypeII

TypeIII

anti-GBMIC

Pauci-immuneIFlinearGBMGranularGBM（-）

deposits&mesangiumdepositsSerumanti-GBMAb(+)C3、CIC70%-80%ANCA（+）Agetheyoung&themiddle-agedthemiddle-agedmiddleaged&aged&agedI型RPGNⅠ型又稱抗腎小球基底膜型急進(jìn)性腎炎好發(fā)于青、中年患者血清抗腎小球基底膜（GBM）抗體陽(yáng)性臨床呈現(xiàn)典型急進(jìn)性腎炎綜合征，極少出現(xiàn)腎病綜合征病理IgG及C3沿腎小球毛細(xì)血管壁呈線樣沉積光鏡下“齊步走”。PekingUniversityTheThirdHospitalRenalDivisionII型RPGNⅡ型又稱免疫復(fù)合物型急進(jìn)性腎炎好發(fā)于中老年部分患者血清循環(huán)免疫復(fù)合物增多，血清補(bǔ)體C3下降除急進(jìn)性腎炎綜合征外，臨床尚常見(jiàn)腎病綜合征病理免疫球蛋白及C3于系膜區(qū)及毛細(xì)血管壁呈顆粒樣沉積PekingUniversityTheThirdHospitalRenalDivisionIII型RPGNⅢ型又稱寡免疫沉積物型急進(jìn)性腎炎好發(fā)于中老年約80%患者血清抗中性白細(xì)胞胞漿自身抗體（ANCA）陽(yáng)性除急進(jìn)性腎炎綜合征外，臨床也常見(jiàn)腎病綜合征，常合并全身多系統(tǒng)損害病理腎小球內(nèi)無(wú)或僅見(jiàn)微量免疫沉積物PekingUniversityTheThirdHospitalRenalDivisionPekingUniversityTheThirdHospitalRenalDivision鑒別診斷

其他原發(fā)性腎小球腎炎-AGN,IgAN,etc

表現(xiàn)為RPGN綜合征的繼發(fā)性腎小球腎炎-GoodpastureSyndrome,

LN,SHP

非腎小球疾病導(dǎo)致的急性腎衰竭

-ATN，AINPekingUniversityTheThirdHospitalRenalDivision治療

一般支持治療

免疫強(qiáng)化治療

腎衰竭-血液凈化治療

利尿

降壓并發(fā)癥的治療PekingUniversityTheThirdHospitalRenalDivision免疫強(qiáng)化治療血漿置換plasmapheresis：適應(yīng)證：I型的首選治療，尤其有肺出血時(shí)方法：2-4L，Qd或Qod，直至血清致病抗體消失或低滴度觀察指標(biāo)：Scr、抗GBM抗體、尿量預(yù)后：無(wú)尿、SCr>600mmol/L、新月體>85%免疫吸附imminoadsorption

PekingUniversityTheThirdHospitalRenalDivision免疫強(qiáng)化治療甲潑尼龍沖擊治療Pulsemethylprednisolonetherapy：10-15mg/kg（0.5-1.0g）qd或qod，×3/course×1-3course，適用于Ⅱ、Ⅲ型急進(jìn)性腎炎，對(duì)抗GBM抗體致病的Ⅰ型急進(jìn)性腎炎療效不確定。序貫1mg/kg/dCTX：根據(jù)腎功能調(diào)整口服1-2mg/kg/div沖擊0.75g/m2

（0.8-1.0/m）KDIGO指南對(duì)I型RPGN的治療推薦14.1:Treatmentofanti-GBMGN14.1.1:Werecommendinitiatingimmunosuppressionwithcyclophosphamideandcorticosteroidsplusplasmapheresisinallpatientswithanti-GBMGNexceptthosewhoaredialysis-dependentatpresentationandhave100%crescentsinanadequatebiopsysample,anddonothavepulmonaryhemorrhage.(1B)14.1.2:Starttreatmentforanti-GBMGNwithoutdelayoncethediagnosisisconfirmed.Ifthediagnosisishighlysuspected,itwouldbeappropriatetobeginhigh-dosecorticosteroidsandplasmapheresiswhilewaitingforconfirmation.(NotGraded)14.1.3:Werecommendnomaintenanceimmunosuppressivetherapyforanti-GBMGN.(1D)14.1.4:Deferkidneytransplantationafteranti-GBMGNuntilanti-GBMantibodieshavebeenundetectableforaminimumof6months.(NotGraded)PekingUniversityThirdHospitalRenalDivisionKDIGO指南對(duì)III型RPGN的治療推薦13.1:Initialtreatmentofpauci-immunefocalandsegmentalnecrotizingGN13.1.1:Werecommendthatcyclophosphamideandcorticosteroidsbeusedasinitialtreatment.(1A)13.1.2:Werecommendthatrituximabandcorticosteroidsbeusedasanalternativeinitialtreatmentinpatientswithoutseverediseaseorinwhomcyclophosphamideiscontraindicated.(1B)13.2:Specialpatientpopulations13.2.1:WerecommendtheadditionofplasmapheresisforpatientsrequiringdialysisorwithrapidlyincreasingSCr.(1C)13.2.2:Wesuggesttheadditionofplasmapheresisforpatientswithdiffusepulmonaryhemorrhage.(2C)13.2.3:WesuggesttheadditionofplasmapheresisforpatientswithoverlapsyndromeofANCAvasculitisandanti-GBMGN,accordingtoproposedcriteriaandregimenforanti-GBMGN(seeChapter14).(2D)13.2.4:Wesuggestdiscontinuingcyclophosphamidetherapyafter3monthsinpatientswhoremaindialysis-dependentandwhodonothaveanyextrarenalmanifestationsofdisease.(2C)PekingUniversityThirdHospitalRenalDivisionPekingUniversityThirdHospitalRenalDivisionKDIGO指南對(duì)III型RPGN的治療推薦PekingUniversityTheThirdHospitalRenalDivision預(yù)后HardlyrelieveMostARFCRFordeathTypeI-worstII-worseIII-badTreatmentAge

慢性腎小球腎炎以不同程度的水腫、高血壓、蛋白尿、血尿及腎功能損害為基本臨床表現(xiàn)起病方式不同、病情遷延、病變緩慢進(jìn)展、病理表現(xiàn)多樣最終可能發(fā)展成慢性腎衰竭治療決策與臨床表現(xiàn)和病理診斷密切相關(guān)PekingUniversityTheThirdHospitalRenalDivision隱匿性腎小球腎炎無(wú)癥狀血尿和/或蛋白尿（小于1.0g/d）無(wú)水腫、高血壓及腎功能損害，大多數(shù)腎功能長(zhǎng)期穩(wěn)定PekingUniversityTheThirdHospitalRenalDivision病例3患者，女，27歲主因“咽痛、血尿2天”來(lái)診。2天前受涼后出現(xiàn)咽痛，伴發(fā)熱37.3℃，尿色呈洗肉水樣，尿量正常，無(wú)水腫，無(wú)尿頻、尿急、尿痛。PekingUniversityTheThirdHospitalRenalDivision病例3查體：T37.0℃，P72次/分，BP120/70mmHg，顏面眼瞼無(wú)水腫，咽充血，扁桃體I度。心肺腹無(wú)陽(yáng)性發(fā)現(xiàn)。雙下肢無(wú)水腫。輔助檢查：

血常規(guī)：正常

尿常規(guī)：蛋白1+，潛血3+，紅細(xì)胞15-20/HP

血生化：ALB42g/L，Cr65μmol/L

免疫：自身抗體（-），免疫球蛋白及補(bǔ)體正常PekingUniversityTheThirdHospitalRenalDivision腎活檢PekingUniversityTheThirdHospitalRenalDivisionIgANephropathyIgA腎病PekingUniversityTheThirdHospitalRenalDivisionOverviewInitiallydescribedbyBergerandHingLaisin1968.predominantIgAdeposition(and,toalesserextent,otherIgs)inthemesangiumwithamesangialproliferationAge-adjustedprevalenceofvariousprimaryglomerulardiseasesPekingUniversityTheThirdHospitalRenalDivisionFrequencyofIgANinprimaryglomerulardiseasesin

differentcountriesPrimaryIgAnephropathySecondaryIgAnephropathy

Sch?nlein-Henochpurpura

HIVinfection

Toxoplasmosis

Seronegativespondyloarthropathy

Celiacdisease

Dermatitisherpetiformis

Crohndisease

Liverdisease

Alcoholiccirrhosis

Ankylosingspondylitis

Reitersyndrome

Neoplasia

Mycosisfungoides

Lung

Mucin-secreting

Cyclicneutropenia

Immunothrombocytopenia

Gluten-sensitiveenteropathy

Scleritis

Siccasyndrome

Mastitis

Pulmonaryhemosiderosis

Bergerdisease

LeprosyFamilialIgAnephropathy免疫機(jī)制血清IgA結(jié)構(gòu)異常IgA1鉸鏈區(qū)核心1β3-半乳糖基轉(zhuǎn)移酶的活性下降，致O-糖鏈末端半乳糖缺失，引起其O-糖基化異常結(jié)構(gòu)的異常，使其轉(zhuǎn)變成自身抗原，誘導(dǎo)抗體產(chǎn)生，形成抗原抗體復(fù)合物，沉積在腎小球系膜上血清IgA1水平升高IgAN的發(fā)病與黏膜感染有關(guān)“黏膜-骨髓軸”：粘膜內(nèi)抗原特定的淋巴細(xì)胞或抗原遞呈細(xì)胞進(jìn)入骨髓，引起骨髓B細(xì)胞分泌IgA增加CurrOpinNephrolHypertens.2004,13(2):171-79PekingUniversityTheThirdHospitalRenalDivision61PekingUniversityTheThirdHospitalRenalDivisionPekingUniversityTheThirdHospitalRenalDivisionPathologyLM:variable4%nolesion13%mesangioproliferativeglomerulonephritis37%focalproliferativeglomerulonephritis28%diffuseproliferativeglomerulonephritis4%crescenticglomerulonephritis6%focalsclerosingglomerulonephritis6%diffusechronicsclerosingglomerulonephritisPekingUniversityTheThirdHospitalRenalDivisionTheOxfordclassificationofIgAnephropathyKI2009,76(5):534～545PekingUniversityTheThirdHospitalRenalDivisionClinicalfeatureclinicalfeaturesthatspannedthespectrumfromasymptomatichematuriatoRPGN.

animportantcauseofprogressive

kidneydiseasePekingUniversityTheThirdHospitalRenalDivisionClinicalfeature80%ofpatientsarebetweentheagesof16and35M:F=2–6:1Asymptomaticurinetestabnormal 30%～40%Hematuria microscopic 100% gross 30%PekingUniversityTheThirdHospitalRenalDivisionProteinuria

NS 3%～4%Hypertension50%inadultpatientSomepresentwithmalignanthypertensionARF <5%CRFClinicalfeaturePekingUniversityTheThirdHospitalRenalDivisionTreatmentACEI/ARB----basicSteroidImmunosuppressiveagentstonsillectomyFishoilSupportivetreatmentPekingUniversityTheThirdHospitalRenalDivisionIgA腎病腎功能正常腎功能不全蛋白尿>3.5g/d蛋白尿1~3.5g/d蛋白尿<1g/d病理輕~中度病理中度病理輕度病理輕度新月體腎炎血管炎病理慢性病變?yōu)橹餮◆?gt;250umol/L慢性腎功能不全非透析治療血肌酐133~250umol/L病理活動(dòng)病變?yōu)橹骷に?CTX/AZA其他ACEI激素強(qiáng)化免疫抑制治療觀察激素ACEIACEI中華內(nèi)科雜志，2004,43:712KDIGOguideline2012Antiproteinuricandantihypertensivetherapy10.2.1:Werecommendlong-termACE-IorARBtreatmentwhenproteinuriais>1g/d,withup-titrationofthedrugdependingonbloodpressure.(1B)10.2.2:WesuggestACE-IorARBtreatmentifproteinuriaisbetween0.5to1g/d(inchildren,between0.5to1g/dper1.73m2).(2D)10.2.3:WesuggesttheACE-IorARBbetitratedupwardsasfarastoleratedtoachieveproteinuria<1g/d.(2C)10.2.4:InIgAN,usebloodpressuretreatmentgoalsof<130/80mmHginpatientswithproteinuria<1g/d,and<125/75mmHgwheninitialproteinuriais>1g/d(seeChapter2).(NotGraded)PekingUniversityTheThirdHospitalRenalDivisionKDIGOguideline201210.3:Corticosteroids10.3.1:Wesuggestthatpatientswithpersistentproteinuria≥1g/d,despite3–6monthsofoptimizedsupportivecare(includingACE-IorARBsandbloodpressurecontrol),andGFR>50ml/minper1.73m2,receivea6-monthcourseofcorticosteroidtherapy.(2C)PekingUniversityTheThirdHospitalRenalDivisionKDIGOguideline201210.4:Immunosuppressiveagents(cyclophosphamide,azathioprine,MMF,cyclosporine)10.4.1:WesuggestnottreatingwithcorticosteroidscombinedwithcyclophosphamideorazathioprineinIgANpatient