狼瘡性腎炎的病理-劉剛

1、狼瘡性腎炎的病理改變狼瘡性腎炎的病理改變 北京大學(xué)第一醫(yī)院腎內(nèi)科北京大學(xué)第一醫(yī)院腎內(nèi)科劉剛劉剛 n重點(diǎn)不在于診斷重點(diǎn)不在于診斷(但要注意合并其它病變但要注意合并其它病變)n分型分型n活動(dòng)性和慢性化指標(biāo)活動(dòng)性和慢性化指標(biāo)n指導(dǎo)治療和判斷預(yù)后指導(dǎo)治療和判斷預(yù)后 腎臟病理腎臟病理LNLN的病理分型的病理分型n自自1974年年WHO首次公布首次公布LN的病理分型的病理分型標(biāo)準(zhǔn)后，又分別在標(biāo)準(zhǔn)后，又分別在1982年、年、1995年及年及2003年進(jìn)行了三次重大修訂。年進(jìn)行了三次重大修訂。 2003 ISN/RPS Consensus Conference on the Classification of

2、 Lupus Nephritis (preliminary)nI: Minimal mesangial lupus glomerulonephritis (LGN)nII: Mesangial proliferative LGNnIII: Focal LGN (involving glomeruli, IV-S and IV-G)nA/CnV: Membranous LGN （可以與（可以與III或或IV重疊）重疊）nVI: Advanced sclerotic LGN (90% sclerotic glomeruli)腎臟病理評(píng)分腎臟病理評(píng)分 活動(dòng)指數(shù)活動(dòng)指數(shù) 慢性指數(shù)慢性指數(shù)n腎小球病變腎

3、小球病變 1. 細(xì)胞增生細(xì)胞增生 1. 腎小球硬化腎小球硬化 2. 纖維素樣壞死、核碎裂纖維素樣壞死、核碎裂2. 纖維性新月體纖維性新月體 3. 細(xì)胞性新月體細(xì)胞性新月體 4. 透明血栓，白金耳透明血栓，白金耳 5. 炎細(xì)胞浸潤(rùn)炎細(xì)胞浸潤(rùn)n腎小管間質(zhì)病變腎小管間質(zhì)病變 1. 單核細(xì)胞浸潤(rùn)單核細(xì)胞浸潤(rùn)1. 間質(zhì)纖維化間質(zhì)纖維化 2. 腎小管萎縮腎小管萎縮Austin et al. 1983病理報(bào)告病理報(bào)告n狼瘡性腎炎狼瘡性腎炎IV-G(A/C)Vn注明特殊病變注明特殊病變n新月體、纖維素樣壞死等新月體、纖維素樣壞死等n腎小管、腎間質(zhì)、血管等腎小管、腎間質(zhì)、血管等新分型帶來(lái)的思考新分型帶來(lái)的思考C

4、lass IV: IV-S vs. IV-G?Comparison of IV-S and IV-G StudiesParameterNajafi HillYokoyamaMittal et alHTNGSGSGSProteinuriaGSGSGSGSScrGSGSGSGSWire loopsGSGSGSSE depositsGSGSInt InflamGSSGInt FibrosisGSGSSGAIGSGSGSSGCISGGSGSSGOutcome S worseGS (ns)GS (ns) GS (ns)Najafi et al KI 2001, Hill et al KI 2005, Y

5、okohama et al KI 2004, Mittal et al AJKD, 2004Our worknRenal histopathological data of 327 patients with renal biopsy proven LNnDiagnosed between January 2000 and July 2008 in Peking University First Hospital Lupus. 2009, 18(12):1073-81. IV-SIV-GP Number of patients20152Gender(male/female)1/1926/126

6、0.207Age (meanSD) (years)34.110.931.310.60.277Number of oral ulcer (%)11(55)40(26.3)0.017Number of anemia (%)12(60)135(88.8)0.003Number of hematuria (%)15(75)144(94.7)0.009Number of nephrotic syndrome (%)8(40)109(71.1)0.009Acute kidney injury (%)1(5)57(37.5)0.002SLEDAI (meanSD)19.45.4719.465.310.962

7、Clinical data IV-SIV-GP valueNumber of patients20152 Hemoglobin (meanSD) (g/L)104.621.892.821.80.024Urine protein (median;range Min-Max) (g/24 hours)3.215,2-125.35,3-210.003Serum creatinine (meanSD) (mg/dL)1.00.272.072.050.021Creatinine clearance rate (meanSD) (ml/min)81.2919.7456.1234.150.002Number

8、 of anti-cardiolipin antibody (%)5/15(33.3)8/98(8.2)0.014C3 (meanSD) (g/L)0.460.190.380.160.045Lab data IV-SIV-GPNumber of biopsies20152 Number of glomeruli(meanSD)32.314.328.211.50.148% of cases with fibrinoid necrosis25(5/20)4.6(7/152)0.006AI score(meanSD)8.752.7310.933.360.006Endocapillary hyperc

9、ellualrity(meanSD)2.350.592.920.340.001Interstitial inflammation(meanSD)1.050.221.510.780.01CI score(meanSD)2.90.973.292.030.90Pathological dataRenal OutcomenThe frequency of serum ANCA was significantly higher in IV-S group than that in IV-G group (20% vs. 4.6%, P=0.008)nThe frequencies of anti-C1q

10、 IgG1 and IgG3 subclass were significantly higher in IV-G group than that in IV-S group (P=0.006, P=0.011, respectively) nCrGN was not rare in patients with LN（33/327） nANCA might play a role in crescent formation.n10/33 vs. 3/119 nAlthough aggressive immunosuppressive therapy could achieve clinical

11、 remission, their long-term renal outcome was poor.nESRD 7/33 vs. 4/119Kidney Int. 2009;76:307-317 Kidney International advance online publication, 24 February 2010n5個(gè)單位協(xié)作個(gè)單位協(xié)作n313例，有例，有2年以上隨訪資料年以上隨訪資料nwe found that the 2003 ISN/RPS classification system of lupus nephritis, based on glomerular lesio

12、ns, could also reflect related tubulointerstitial lesions. n141/313n腎小球病變重、腎間質(zhì)小管病變輕腎小球病變重、腎間質(zhì)小管病變輕n15/313n腎小球病變輕、腎間質(zhì)小管病變重腎小球病變輕、腎間質(zhì)小管病變重nIn multivariate Cox hazard analysis of tubulointerstitial lesions, indices of interstitial infiltration, tubular atrophy, and interstitial fibrosis were confirmed

13、as significant independent risk factors for renal outcome. 小結(jié)小結(jié)n狼瘡性腎炎病理分型尚需根據(jù)證據(jù)不斷狼瘡性腎炎病理分型尚需根據(jù)證據(jù)不斷修訂修訂n特殊病變可能具有獨(dú)特的內(nèi)在機(jī)制和臨特殊病變可能具有獨(dú)特的內(nèi)在機(jī)制和臨床特點(diǎn)床特點(diǎn)n腎間質(zhì)小管病變對(duì)預(yù)后的影響更大腎間質(zhì)小管病變對(duì)預(yù)后的影響更大TTP-HUS in LNnTwelve patients with evidence of TMA were identified in 353 patients with LNnSeven out of the 12 patients were d

14、iagnosed as TTP-HUSLN+TTP-HUSLNP valueNumber of patients755Gender(male/female)1/610/451.0Age (meanSD) (years)29.012.031.710.20.52Hemoglobin (meanSD) (g/L)75.622.495.621.60.022Number of LDH elevated (%)7(100)2(3.6)0.001Number of schistocytes presence(%)6(85.8)0(0)0.001Number of thrombocytopenia (%)7(

15、100)8(14.5)0.001Platelet count (meanSD) (x109/L)64.723.0161.972.20.001Acute renal injury (%)6(85.8)6(10.9)0.001Serum creatinine (meanSD) (mg/dL)5.13.41.21.0 0.5g/d或或+）和和/或管型尿，明確診斷為或管型尿，明確診斷為L(zhǎng)N者者 。 （3）在我院行腎活檢并有完整的臨床、病理及隨訪資料。）在我院行腎活檢并有完整的臨床、病理及隨訪資料。 （4）腎穿刺標(biāo)本中腎小球數(shù)目）腎穿刺標(biāo)本中腎小球數(shù)目10個(gè)個(gè) ，小動(dòng)脈數(shù)目，小動(dòng)脈數(shù)目6個(gè)。個(gè)。 Art

16、hritis Rheum.1997病理評(píng)估：病理評(píng)估： （1 1）病理分型及評(píng)分：）病理分型及評(píng)分： 按照按照2003年年ISN/RPS制定的制定的LN病理分型標(biāo)準(zhǔn)病理分型標(biāo)準(zhǔn)進(jìn)行分型；進(jìn)行分型； 按照按照NIH（National Institutes of Health）評(píng)）評(píng)分體系進(jìn)行活動(dòng)性和慢性化指標(biāo)評(píng)分。分體系進(jìn)行活動(dòng)性和慢性化指標(biāo)評(píng)分。 Kidney Int. 2004 Kidney Int. 1984（2 2）腎血管病變?cè)u(píng)分）腎血管病變?cè)u(píng)分 LN血管病變類型血管病變類型Vascular Immune Complex Deposits (ICD) Noninflammatory Necrotizing Vasculopathy (NNV)Thrombotic Microangiopathy (TMA)True Renal Vasculitis (TRV)Arteriosclerosis (AS) J. Am. Soc. Nephrol. 1994新新AI和和CI血管病變活動(dòng)性病變?cè)u(píng)分血管病變活動(dòng)性病變?cè)u(píng)分 ICD (0, 1) NNV (0, 1) TMA A/A 和和/或