1、內科學腎小球疾病（英文版）Glomerular DiseasesThe peripheral portion of a glomerular lobuleGlomerular Diseases ClassificationPrimarySecondaryHereditaryPathogenesisImmunologic glomerular injuryHumoral antibody-mediatedCellular antibody-independent Antibody-mediatedCirculating autoantibodies with intrinsic autoanti

2、gens: eg. anti-GBM diseaseIn situ formation of immune complexs/ circulationg antibodies with extrinsic antigens that have been “planted” within the glomerulus: eg. Postinfectious glomerulonephritisANCA/AECA associated: no disernible immune complexes in the glomerular parenchymaCellular antibody-inde

3、pendent glomerular injuryLess well definedInitiators of injury in pauci-immune glomerulonephritis, which share the downstream mediators with the antibody-dependent injurySoluble factors from T cells: in MCD and primary FSGSNonimmunologic glomerular injuryMetabolicHemodynamictoxic immunologichumoralc

4、ellularnon-immunologicinflammationGlomerular injuryClinicopathologic correlates in glomerular diseaseMajor clinicopathologic entities (contd)Nephrotic syndromeGlomerular filtration barrier affectedHypoalbuminemia, edema, hyperlipidemia, and lipiduria, and a prothrombotic stateMembranous glomerulopat

5、hyMinimal change disease (MCD)FSGSMembranoproliferative: hybrid lesion of nephritic and nephrotic featuresOthersGlomerular deposition diseases: extravascular deposition of paraprotein or fibrillar materialThrombotic microangiopathies: thrombi within the renal microvasculaturePrimary insultInflammato

6、ryMetabolic Hemodynamic or mechanic ToxicInfectiousMay overlapMay induce similar clinicopahtologic presentations病變部位 系膜 mesangium 系膜細胞 mesangial cell 系膜基質 mesangial matrix 基膜 basement membrane 上皮細胞 足細胞 podocyte、 足突 foot process 內皮細胞The peripheral portion of a glomerular lobule 基本病變 增生 proliferation

7、硬化 sclerosis1.輕微腎小球病變（Minor Lesion) 無特異性病變 光鏡下可見輕度系膜細胞增生和 系膜基質增多輕微病變腎病 minimal change disease，MCD輕度系膜增殖性腎小球腎炎毛細血管內增殖性腎小球腎炎恢復期其它MCD （左）正常，（右）上皮細胞足突廣泛融合、消失2. 局灶節(jié)段性病變(1)局灶節(jié)段性增殖性腎小球腎炎 focal and segmental proliferative glomerulonephritis (2)局灶節(jié)段性腎小球硬化 focal and segmental glomerulosclerosis, FSGS局灶性腎小球腎炎

8、3.彌漫性腎小球腎炎 (diffusive glomerulonephritis)(1)膜性腎病 membranous nephropathy, MN 腎小球基底膜 membranous nephropathy （左）正常，（右）上皮下免役復合物沉積（D），GBM增厚，釘突形成（S），上皮細胞足突融合(2)增殖性腎小球腎炎 proliferative glomerulonephritis系膜增殖性腎小球腎炎 mesangial proliferative glomerulonephritis MsPGN 腎小球系膜IgA腎病 IgA nephropathy非IgA腎病 IgG沉積為主 IgM腎

9、病mesangial proliferative glomerulonephritis（左）正常，（右）系膜細胞和基質增生，電子致密物（D）沉積 毛細血管內增殖性腎小球腎炎 endocapillary proliferative glomerulonephritis 系膜+內皮細胞endocapillary proliferative glomerulonephritis （左）正常，（右）內皮（E）和系膜（M）細胞增生，上皮下駝峰狀電子致密物（D）沉積 系膜毛細血管性腎小球腎炎 mesangiocapillary glomerulonephritis 又稱膜增殖性腎小球腎炎 membrano

10、proliferative glomerulonephritis 系膜+基底膜致密沉積物性腎小球腎炎 dense desposit glomerulonephritis 電子致密沉積物mesangiocapillary glomerulonephritis （左）正常，（右）系膜增生（M），電子致密物（D），廣泛插入（I） 新月體性腎小球腎炎 cresentic glomerulonephritis 又稱毛細血管外腎小球腎炎 extracapillary glomerulonephritis 腎小球囊上皮細胞(3) 硬化性腎小球腎炎 sclerosing glomerulonephritisc

11、resentic glomerulonephritis （左）正常，（右）GBM斷裂，纖維蛋白漏出(F)，上皮細胞增生(E)，單核巨噬細胞浸潤(P)，新月體形成 4.未分類的腎小球腎炎 unclassified glomerulonephritisClinical presentationsClinical classificationAcute glomerulonephritis,AGNRapidly progressive glomerulonephritis, RPGNChonic glomerulonephritis,CGNNephrotic syndrome,NSLatent gl

12、omerulonephritis, asymptomatic hematuria and/or proteinuriaAcute nephritic syndromeSudden onset (days to weeks)Nephritic urinary sedimentHematuria:Red blood casts, dysmorphic red blood cellsSubnephrotic proteinuria (20% adults may have persistent proteinuria and/or compromise of GFRRPGNOver weeks to

13、 monthsNephritic urinary sediment, subnephrotic proteinuria and variable oliguria, hypervolemia, edema, and hypertensionCrescentic GNCrenscents can also develop concomitantly with proliferative GN, membranous GN and other GNRPGN-Immunofluorescence microscopyanti-GBM dis-more discrete linear depositi

14、on of Ig along the GBMimmune complex GN-scattered granular deposits of immunoglobulinpauci-immune GN-paucity or absence of IgRPGN-Serologic markersDepressed C3 level -Type IIanti-GBM antibody-Type IANCA-Type IIIMay overlapAnti-GBM disease (Goodpastures syndrome)Antibody to a3 chain (noncollagenous d

15、omain) of type IV collagen, which preferentially expressed in glomerular and pulmonary alveolar basement membraneRPGN/crescentic GN, hematuria, nephritic urinary sediment, subnephrotic proteinuria50-70% have lung hemorrhage with hemoptysis or severe alveolar hemorrhageAnti-GBM lab testsAnti-GBM anti

16、bodiesRenal biopsy, gold standard for diagnosis of anti-GBM nephritisDiffuse proliferative GNFocal necrotizing lesionsCrescents in 50% of glomeruliLinear ribbon-like deposition of IgG along the GBMpauci-immune RPGNIdiopathic renal-limited crescentic GNMicrosopic polyangiitis nodosaWegeners granuloma

17、tosisChurg-strauss syndromeAll-encompassing term: ANCA-associated small vessel vasculitisANCA-associated renal diseaseLethargy, malaise, anorexia, weight loss, fever, arthralgias, myalgiasElevated ESR/CRP, leukocytosis, thrombocytosis, normochromic normocytic anemia, complement level typically norma

18、lNephritic urine sediment and subnephrotic proteinuriaRenal dysfunctionBiopsy: focal segmental necrotizing GN with crescent formationPaucity or absence of Ig, complement and immune deposits RPGN I型 II型 III型 抗基膜抗體型 免疫復合物型 非免疫復合物型IF 線樣、沿基膜 顆粒樣、系膜 （-） 區(qū)和基膜 GBM抗體（+）C3、CIC 70%-80%為微 血管炎 ANCA陽性 青、中年 中、老年

19、中、老年 我國多見treatmentGlucocorticoid, pulse treatment and maintenance treatmentCTX or AZAplasmaphereses, immunoadsorptionBetter prognosis in relatively early cases (Scr 3.5 g/24hEdemaHyperlipidemia, lipiduria and hypercoagulabilityMain entities of NSMinimal change disease, MCDFocal and segmental glomeru

20、losclerosis, FSGSMembranous glomerulopathy, MNMsPGNMembranoproliferative glomerulonephritis, MPGNDiabetic nephropahy, DNAmyloidosis,MMComplications-thrombosis deep vein thrombosis renal vein thrombosis Sudden onset of flank or abdominal painGross hematuriaA left-sided varicoceleIncreased proteinuria

21、Acute decline in GFRPaticularly common in MN/MPGN/AmyloidosisOther complicationsProtein malnutritioninfectionNS- treatmentSpecific treatment of the underlying diseaseGlucocorticoid, immunosuppressionGeneral measures of proteinuria controlACEI/ARBNephrotic complications control and preventionSensetiv

22、ity of steroid prednisone(prednisolone)1mg/kg/d 8w negetive proteinuria remain positive relapse during taper sentsetiveSteroid-dependentresistanceNS complications controlEdemaSalt restriction 1-2g/d; judicious use of loop diuretics;Lipid loweringHMG CoA reductaseAnticoagulationIndications: deep veno

23、us thrombosis, arterial thrombosis, pulmonary embolismMinimal change disease, MCD80% of NS in children younger than 16 yo, 20% in adultsGlomerular size and architecture normal by light microscopyIF microscopy negative for Ig and C3EM characteristic diffuse effacement of foot processes of visceral ep

24、ithelial cellsMCD- proteinuria selectivity Selective proteinuria in children with albumin principally and minimal amounts of higher molecular weight protiensSelectivity poor in adults suggesting more extensive perturbation of membraneMCD-treatmentHighly steroid-responsiveGenerally excellent prognosi

25、sRemission after 8 weeks of high-dose oral glucocorticoids: 90% in children and 50% in adultsMCD-treatment (contd)Relapses common following withdrawal of glucocorticoidsAlkylating agents reserved for steroid-resistant, steroid-dependent or frequently relapsing: CTX, chlorambucil, azathioprine, cyclo

26、sporineFocal segmental glomerulosclerosis, FSGSSclerosis with hyalinosis involving portions (segmental) of fewer than 50% (focal) of glomeruliIdiopathic FSGS: Nephrotic syndrome (2/3) or subnephrotic proteinuria (1/3), nonselectiveHypertension, mild renal insufficiency, abnormal urine sedimentFSGS (

27、contd)IdiopathicSecondary: a potential long-term consequence of nephron loss (50%) from any causeCongenital oligomeganephronia, extensive surgical ablation of renal mass, reflux nephropathy, GN, interstitial nephritis, sickle cell disease, ischemia, cyclosporine nephrotoxicity, rejection of allograf

28、tFSGS- treatmentRenal prognosis relatively poorRemission rates for 8 week glucocorticoids: 20-40%, up to 70% for prolonged therapy (16-24 weeks)Immunosuppressants: CTX, cyclosporine, MMFPoor prognostic factors: hypertension, abnormal renal function, persistent heavy proteinuriaMembranous glomerulopa

29、thy (membranous nephropathy, MN)Peak incidence 30-50 years of ageMale:femal 2:1Named after light micrscopic: diffuse GBM thickening80% represents with NS, nonselectiveMicroscopic hematuria 50%MN- pathologyLM: Diffuse thickening of GBM without inflammation or cellular proliferationIF: granular deposi

30、tion of IgG, C3 and terminal components of complements along the glomerular capillary wall MN - pathogenesisIdiopathic MN incompletely understoodImmune deposits suggesting an immune process1/3 with systemic disease: SLE, infections such as hepatitis B, malignancy, drug (eg. gold and penicillamine)MN

31、- treatment and prognosisremits spontaneously and completely in up to 40% another 30 to 40% repeated relapses and remissionsThe final 10 to 20% slow progressive decline in GFR that typically culminates in ESRD after 10 to 15 yearsPoor prognosis indicators: male gender, older age, hypertension, sever

32、e proteinuria and hyperlipidemia, and impaired renal functionControlled trials of glucocorticoids have failed to show consistent improvement in proteinuria or renal protection. Cyclophosphamide, chlorambucil, and cyclosporine have each been shown to reduce proteinuria and/or slow the decline in GFR

33、in patients with progressive disease in small or uncontrolled studies. Membranoproliferative glomerulonephritis, MPGNthickening of the GBM and proliferative changes on light microscopy type I MPGN: subendothelial and mesangial deposits on electron microscopy that contain C3 and IgG or IgM; rarely, I

34、gA deposits type II MPGN (dense deposit disease): electron-dense deposits within the GBM and other renal basement membranes (shown by electron microscopy) that stain for C3, but little or no immunoglobulin. MPGN type I- clinical featuresType IAn immune-complex (IC) GNnephrotic syndrome, active urina

35、ry sediment, and normal or mildly impaired GFR. C3 levels usually depressed, and C1q and C4 levels borderline or low Associated with infections, systemic IC diseases (SLE, cryoglobulinemia), malignancies50% of patients reach ESRD by 10 years MPGN type II- clinical featuresType IIan autoimmune disease with an IgG autoantibody, termed C3 nephritic factorproteinuria and n