1、肾小球肾炎 Glomerulonephritis,北医三院 肾内科 王松,Peking University The Third Hospital Renal Division,内容,正常肾脏结构与功能 原发性肾小球疾病概述 肾病综合征（NS） 急性感染后肾小球肾炎（APGN） 急进性肾小球肾炎（RPGN） IgA肾病 （IgAN）,一组疾病 病变部位在肾小球 病因、发病机制、临床表现、病理、治疗、预后相似或相异,Peking University The Third Hospital Renal Division,肾小球疾病分类,按病因 按发病机制 按临床表现 按病理,Peking Univ
2、ersity The Third Hospital Renal Division,肾小球疾病的病因分类,原发性 原因暂时不明 继发性 全身疾病的一部分 SLE 过敏性紫癜 糖尿病 肿瘤 遗传性,Peking University The Third Hospital Renal Division,肾小球疾病的发病机制及其分类,免疫介导,体液免疫异常 循环免疫复合物致病 如SLE，IgAN 肾脏原位免疫复合物 如GBM、PLA2R 细胞免疫异常,非免疫介导,血液动力学异常 内分泌代谢异常 遗传学异常,Peking University The Third Hospital Renal Divis
3、ion,按临床表现分类,肾病综合征（Nephrotic syndrome） 急性肾炎综合征（Acute nephritic syndrome） 急进性肾炎综合征（ Rapidly progressive nephritic syndrome ） 慢性肾炎综合征（Chronic nephritic syndrome） 隐匿型肾小球肾炎（Latent nephritic syndrome）,Peking University The Third Hospital Renal Division,Spectrum of primary glomerular diseases,Nephrol Dial
4、Transplant (2009) 24: 870876,肾小球疾病的病理分型 （WHO，1982）,轻微病变性肾病（MCN） 局灶性节段性肾小球肾炎（FSGN） 弥漫性肾小球肾炎（Diffuse GN） 增生性 系膜增生性（MsPGN） 毛细血管内增生性 （ECGN） 系膜毛细血管内增生性（ MPGN) 电子致密物沉积性（DDD） 新月体性(Crescentic GN) 膜性肾病（MN） 硬化性（Sclerosis GN） 不易分类的肾小球病,Peking University The Third Hospital Renal Division,肾小球疾病的诊断及格式,病因诊断 临床诊断 病
5、理诊断 功能诊断 并发疾病诊断,Peking University The Third Hospital Renal Division,KDIGO guideline 2012,Peking University The Third Hospital Renal Division,病例1,患者，女，11岁 主因“水肿，少尿，茶色尿1周”来诊。 3周前上感，咽痛，发热38.3，外院用头孢类抗生素及阿奇霉素治疗，体温恢复正常 1周来出现颜面及双下肢水肿，尿色呈浓茶色，尿量显著减少，约600-700ml/日,Peking University The Third Hospital Renal Div
6、ision,病例1,查体：T37.0，P 102次/分，BP 160/100 mmHg，颜面眼睑水肿，全身浅表淋巴结未触及。双肺呼吸音清，未闻及干湿罗音，心界不大，HR 102 次/分，律齐，未闻及杂音。腹软，肝脾未触及，移动性浊音（-）。双下肢可凹性水肿。,Peking University The Third Hospital Renal Division,病例1,辅助检查： 血常规：Hb 115g/L，WBC，Plt正常 尿常规：蛋白3+，潜血3+，比重1.020，红细胞25-30/HP，白细胞3-5/HP 血生化：ALB 35g/L，BUN 8.0 mmol/L，Cr 105 mol/
7、L 免疫：自身抗体（-），免疫球蛋白正常，C3 0.364,Peking University The Third Hospital Renal Division,肾活检,Peking University The Third Hospital Renal Division,Acute Post-Streptococcal Glomerulonephritis 急性链球菌感染后肾小球肾炎,Peking University The Third Hospital Renal Division,病因,A型溶血性链球菌致肾炎菌株 呼吸道感染 猩红热 脓疱疮 病毒 其他病原体,Peking Unive
8、rsity The Third Hospital Renal Division,发病机理,链球菌致肾炎菌株,菌内物质（ESS),菌株伴随蛋白（NSAP),阳电荷菌体外成分,神经氨酸酶？,循环免疫 复合物,原位免疫 复合物,与GBM交叉 抗原性,诱发自体 免疫,细胞介导 免疫,激活补体及各种炎症介质,肾小球炎症病变,内皮细胞肿胀，系膜细胞增生,毛细血管腔闭塞,肾小球滤过面积，GFR,球管失衡,水钠潴留，血容量扩张,肾小球基底膜破坏,蛋白尿 血尿 管型尿,氮质血症，尿毒症,少尿，无尿,水肿，高血压，心衰,Peking University The Third Hospital Renal Divi
9、sion,Peking University The Third Hospital Renal Division,病理,LM： 弥漫毛细血管内增生 IF： IgG和C3，粗颗粒状，沿毛细血管壁及系膜区沉积 EM： 上皮下“驼峰样”电子致密物,Peking University The Third Hospital Renal Division,临床表现,高发年龄2 - 6岁 前驱感染史 潜伏期7 - 21 天 急性起病 急性肾炎综合征 acute nephritic syndrome,Peking University The Third Hospital Renal Division,Pek
10、ing University The Third Hospital Renal Division,合并症,Peking University The Third Hospital Renal Division,辅助检查,尿常规： 100% 血尿，RBC casts 蛋白尿 ：轻-中 肾功能：一过性 GFR 其他： ASO C3(4-8w) CIC+，cryoglobulins + 贫血,Peking University The Third Hospital Renal Division,治疗,一般治疗 卧床休息 饮食: 低盐（每日食盐3g） 利尿 降压 抗感染 透析 少尿、急性肾衰竭、高钾血
11、症,病例2,患者，女，40岁 主因“血尿1月，水肿，少尿1周”来诊。 1月前无诱因出现洗肉水样尿，无血丝、血块，不伴尿频、尿急、尿痛，无发热、腰痛。服云南白药治疗，血尿无好转。 1周来尿量显著减少，约200ml/日，出现双下肢水肿、纳差。,Peking University The Third Hospital Renal Division,病例2,查体：T37.5，P 90次/分，BP 150/95 mmHg，颜面眼睑水肿，全身浅表淋巴结未触及。双肺呼吸音清，未闻及干湿罗音，心界不大，HR 90 次/分，律齐，未闻及杂音。腹软，肝脾未触及，移动性浊音（-）。双下肢可凹性水肿。,Peking
12、University The Third Hospital Renal Division,病例2,辅助检查： 血常规：Hb 90 g/L，WBC，Plt正常 尿常规：蛋白3+，潜血3+，比重1.025，RBC满视野/HP，WBC1-3/HP 血生化：ALB 32g/L，BUN 28.0 mmol/L，Cr 568 mol/L 免疫：GBM抗体1:180，ANA(-)，dsDNA(-)，ANCA（-）,Peking University The Third Hospital Renal Division,肾活检,Peking University The Third Hospital Renal
13、 Division,Rapidly progressive glomerulonephritis (RPGN),急进性肾小球肾炎,Peking University The Third Hospital Renal Division,概述,Acute onset Rapidly progressive Acute nephritic syndrome Renal failure within a few weeks to a few months Pathology Crescent GN,Peking University The Third Hospital Renal Division,
14、Peking University The Third Hospital Renal Division,Peking University The Third Hospital Renal Division,1.原发性RPGN Crescent GN 2.继发性RPGN SLE, SHP, etc,RPGN,RPGN分型,Peking University The Third Hospital Renal Division,Type I Type II Type III anti-GBM IC Pauci-immune IF linear GBM Granular GBM （-） deposi
15、ts & mesangium deposits Serum anti-GBM Ab(+) C3、CIC 70%-80% ANCA （+） Age the young & the middle-aged the middle-aged middle aged & aged & aged,I型RPGN,型又称抗肾小球基底膜型急进性肾炎 好发于青、中年 患者血清抗肾小球基底膜（GBM）抗体阳性 临床呈现典型急进性肾炎综合征，极少出现肾病综合征 病理IgG及C3沿肾小球毛细血管壁呈线样沉积光镜下“齐步走”。,Peking University The Third Hospital Renal Divi
16、sion,II型RPGN,型又称免疫复合物型急进性肾炎 好发于中老年 部分患者血清循环免疫复合物增多，血清补体C3下降 除急进性肾炎综合征外，临床尚常见肾病综合征 病理免疫球蛋白及C3于系膜区及毛细血管壁呈颗粒样沉积,Peking University The Third Hospital Renal Division,III型RPGN,型又称寡免疫沉积物型急进性肾炎 好发于中老年 约80%患者血清抗中性白细胞胞浆自身抗体（ANCA）阳性 除急进性肾炎综合征外，临床也常见肾病综合征，常合并全身多系统损害 病理肾小球内无或仅见微量免疫沉积物,Peking University The Third
17、 Hospital Renal Division,Peking University The Third Hospital Renal Division,鉴别诊断,其他原发性肾小球肾炎 - AGN, IgAN, etc 表现为RPGN综合征的继发性肾小球肾炎 - Goodpasture Syndrome, LN, SHP 非肾小球疾病导致的急性肾衰竭 - ATN，AIN,Peking University The Third Hospital Renal Division,治疗,一般支持治疗 免疫强化治疗 肾衰竭-血液净化治疗 利尿 降压 并发症的治疗,Peking University Th
18、e Third Hospital Renal Division,免疫强化治疗,血浆置换plasmapheresis ： 适应证：I型的首选治疗，尤其有肺出血时 方法：2-4L，Qd或Qod，直至血清致病抗体消失或低滴度 观察指标：Scr、抗GBM抗体、尿量 预后：无尿、SCr600mmol/L、新月体85% 免疫吸附imminoadsorption,Peking University The Third Hospital Renal Division,免疫强化治疗,甲泼尼龙冲击治疗Pulse methylprednisolone therapy： 10-15 mg/kg（0.5 -1.0g）q
19、d或qod， 3/course 1-3 course，适用于、型急进性肾炎，对抗GBM抗体致病的型急进性肾炎疗效不确定。 序贯 1mg/kg/d CTX：根据肾功能调整 口服 1-2 mg/kg/d iv 冲击 0.75 g/m2 （0.8-1.0/m）,KDIGO指南对I型RPGN的治疗推荐,14.1: Treatment of anti-GBM GN 14.1.1: We recommend initiating immunosuppression with cyclophosphamide and corticosteroids plus plasmapheresis in all pa
20、tients with anti-GBM GN except those who are dialysis-dependent at presentation and have 100% crescents in an adequate biopsy sample, and do not have pulmonary hemorrhage. (1B) 14.1.2: Start treatment for anti-GBM GN without delay once the diagnosis is confirmed. If the diagnosis is highly suspected
21、, it would be appropriate to begin high-dose corticosteroids and plasmapheresis while waiting for confirmation. (Not Graded) 14.1.3: We recommend no maintenance immunosuppressive therapy for anti-GBM GN. (1D) 14.1.4: Defer kidney transplantation after anti-GBMGN until anti-GBM antibodies have been u
22、ndetectable for a minimum of 6 months. (Not Graded),Peking University Third Hospital Renal Division,KDIGO指南对III型RPGN的治疗推荐,13.1: Initial treatment of pauci-immune focal and segmental necrotizing GN 13.1.1: We recommend that cyclophosphamide and corticosteroids be used as initial treatment. (1A) 13.1.
23、2: We recommend that rituximab and corticosteroids be used as an alternative initial treatment in patients without severe disease or in whom cyclophosphamide is contraindicated. (1B) 13.2: Special patient populations 13.2.1: We recommend the addition of plasmapheresis for patients requiring dialysis
24、 or with rapidly increasing SCr. (1C) 13.2.2: We suggest the addition of plasmapheresis for patients with diffuse pulmonary hemorrhage.(2C) 13.2.3: We suggest the addition of plasmapheresis for patients with overlap syndrome of ANCA vasculitis and anti-GBM GN, according to proposed criteria and regi
25、men for anti-GBM GN (see Chapter 14). (2D) 13.2.4: We suggest discontinuing cyclophosphamide therapy after 3 months in patients who remain dialysis-dependent and who do not have any extrarenal manifestations of disease. (2C),Peking University Third Hospital Renal Division,Peking University Third Hos
26、pital Renal Division,KDIGO指南对III型RPGN的治疗推荐,Peking University The Third Hospital Renal Division,预后,Hardly relieve Most ARFCRF or death Type I-worst II-worse III-bad Treatment Age,慢性肾小球肾炎,以不同程度的水肿、高血压、蛋白尿、血尿及肾功能损害为基本临床表现 起病方式不同、病情迁延、病变缓慢进展、病理表现多样 最终可能发展成慢性肾衰竭 治疗决策与临床表现和病理诊断密切相关,Peking University The T
27、hird Hospital Renal Division,隐匿性肾小球肾炎,无症状血尿和/或蛋白尿（小于1.0g/d） 无水肿、高血压及肾功能损害，大多数肾功能长期稳定,Peking University The Third Hospital Renal Division,病例3,患者，女，27岁 主因“咽痛、血尿2天”来诊。 2天前受凉后出现咽痛，伴发热37.3，尿色呈洗肉水样，尿量正常，无水肿，无尿频、尿急、尿痛。,Peking University The Third Hospital Renal Division,病例3,查体：T37.0，P 72次/分，BP 120/70 mmHg，
28、颜面眼睑无水肿，咽充血，扁桃体I度。心肺腹无阳性发现。双下肢无水肿。 辅助检查： 血常规：正常 尿常规：蛋白1+，潜血3+，红细胞15-20/HP 血生化：ALB 42g/L，Cr 65 mol/L 免疫：自身抗体（-），免疫球蛋白及补体正常,Peking University The Third Hospital Renal Division,肾活检,Peking University The Third Hospital Renal Division,IgA Nephropathy,IgA肾病,Peking University The Third Hospital Renal Divis
29、ion,Overview,Initially described by Berger and HingLais in 1968. predominant IgA deposition (and, to a lesser extent, other Igs) in the mesangium with a mesangial proliferation,Age-adjusted prevalence of various primary glomerular diseases,Peking University The Third Hospital Renal Division,Frequenc
30、y of IgAN in primary glomerular diseases in different countries,免疫机制,血清IgA结构异常 IgA1铰链区核心13 - 半乳糖基转移酶的活性下降，致O-糖链末端半乳糖缺失，引起其O-糖基化异常 结构的异常，使其转变成自身抗原，诱导抗体产生，形成抗原抗体复合物，沉积在肾小球系膜上 血清IgA1水平升高 IgAN 的发病与黏膜感染有关 “黏膜- 骨髓轴”：粘膜内抗原特定的淋巴细胞或抗原递呈细胞进入骨髓，引起骨髓B细胞分泌IgA增加 CurrOp in Nephrol Hypertens.2004,13 (2):171-79,Peki
31、ng University The Third Hospital Renal Division,61,Peking University The Third Hospital Renal Division,Peking University The Third Hospital Renal Division,Pathology,LM: variable 4% no lesion 13% mesangioproliferative glomerulonephritis 37% focal proliferative glomerulonephritis 28% diffuse prolifera
32、tive glomerulonephritis 4% crescentic glomerulonephritis 6% focal sclerosing glomerulonephritis 6% diffuse chronic sclerosing glomerulonephritis,Peking University The Third Hospital Renal Division,The Oxford classification of IgA nephropathy,KI 2009,76(5):534545,Peking University The Third Hospital
33、Renal Division,Clinical feature,clinical features that spanned the spectrum from asymptomatic hematuria to RPGN. an important cause of progressive kidney disease,Peking University The Third Hospital Renal Division,Clinical feature,80% of patients are between the ages of 16 and 35 M:F = 2 6 : 1 Asymp
34、tomatic urine test abnormal 30%40% Hematuria microscopic 100% gross 30%,Peking University The Third Hospital Renal Division,Proteinuria NS 3%4% Hypertension 50% in adult patient Some present with malignant hypertension ARF 5% CRF,Clinical feature,Peking University The Third Hospital Renal Division,T
35、reatment,ACEI/ARB-basic Steroid Immunosuppressive agents tonsillectomy Fish oil Supportive treatment,Peking University The Third Hospital Renal Division,IgA肾病,肾功能正常,肾功能不全,蛋白尿3.5g/d,蛋白尿13.5g/d,蛋白尿1g/d,病理 轻中度,病理 中度,病理 轻度,病理 轻度,新月体肾炎 血管炎,病理 慢性病变为主,血肌酐 250umol/L,慢性肾功 能不全非 透析治疗,血肌酐 133250umol/L,病理 活动病变为主
36、,激素+ CTX/AZA 其他,ACEI 激素,强化 免疫抑制 治疗,观察,激素 ACEI,ACEI,中华内科杂志，2004,43:712,KDIGO guideline 2012,Antiproteinuric and antihypertensive therapy 10.2.1: We recommend long-term ACE-I or ARB treatment when proteinuria is 1 g/d, with up-titration of the drug depending on blood pressure. (1B) 10.2.2: We suggest
37、ACE-I or ARB treatment if proteinuria is between 0.5 to 1 g/d (in children, between 0.5 to 1 g/d per 1.73m2). (2D) 10.2.3: We suggest the ACE-I or ARB be titrated upwards as far as tolerated to achieve proteinuria 1 g/d (see Chapter 2). (Not Graded),Peking University The Third Hospital Renal Divisio
38、n,KDIGO guideline 2012,10.3: Corticosteroids 10.3.1: We suggest that patients with persistent proteinuria 1 g/d, despite 36 months of optimized supportive care (including ACE-I or ARBs and blood pressure control), and GFR50 ml/min per 1.73m2, receive a 6-month course of corticosteroid therapy. (2C),
39、Peking University The Third Hospital Renal Division,KDIGO guideline 2012,10.4: Immunosuppressive agents (cyclophosphamide, azathioprine, MMF, cyclosporine) 10.4.1: We suggest not treating with corticosteroids combined with cyclophosphamide or azathioprine in IgAN patients (unless there is crescentic
40、 IgAN with rapidly deteriorating kidney function; see Recommendation 10.6.3). (2D) 10.4.2: We suggest not using immunosuppressive therapy in patients with GFR 30 ml/min per 1.73m2 unless there is crescentic IgAN with rapidly deteriorating kidney function(see Section 10.6). (2C) 10.4.3: We suggest no
41、t using MMF in IgAN. (2C),Peking University The Third Hospital Renal Division,KDIGO guideline 2012,10.5: Other treatments 10.5.1: Fish oil treatment 10.5.1.1: We suggest using fish oil in the treatment of IgAN with persistent proteinuria 1 g/d, despite 36 months of optimized supportive care (includi
42、ng ACE-I or ARBs and blood pressure control). (2D) 10.5.2: Antiplatelet agents 10.5.2.1: We suggest not using antiplatelet agents to treat IgAN. (2C) 10.5.3: Tonsillectomy 10.5.3.1: We suggest that tonsillectomy not be performed for IgAN. (2C),Peking University The Third Hospital Renal Division,Peki
43、ng University The Third Hospital Renal Division,Aged ProU Hypertension Pathology Renal insufficiency,Prognosis,Peking University The Third Hospital Renal Division,Natural history,Predictive factors of prognosis,Reich HN, et al. J Am Soc Nephrol 2007, 18: 3177,Peking University The Third Hospital Renal Division,Predictive factors of prognosis,Peking University The Third Hospital Renal Division,Predictive factors of prognosis,Peking University The Third Hospital Renal Division,Q & A,肾小球疾病的诊断包括哪些内容？ 急进性肾小球肾炎的分型及治疗？,Peking University The Third Hospital Renal Division,Thank you！,
