抗肾小球基膜肾炎合并糖尿病肾病

中年男性,以持续肉眼血尿伴大量蛋白尿、肾功能减退、血抗肾小球基膜( GBM)抗体阳性起病；肾活检组织学符合新月体肾炎,免疫荧光见IgG沿肾小球毛细血管袢线性沉积,符合抗GBM肾炎,同时亦见肾小球呈结节样改变、肾小管基膜(TBM)增厚、动脉透明变性等,超微结构观察GBM呈均匀一致性增厚,经糖耐量检查确诊糖尿病.该患者最终诊断为抗GBM肾炎合并糖尿病肾病(DN).     

抗肾小球基膜肾炎合并膜性肾病

青年男性患者,临床表现急进性肾炎综合征伴大量蛋白尿、低蛋白血症,血清抗肾小球基膜(GBM)抗体阳性,肾活检组织学呈新月体肾炎合并膜性肾病,免疫病理IgG呈线状及颗粒状沉积于血管袢,电镜下见GBM上皮侧电子致密物沉积,最终诊断为抗GBM肾炎合并膜性肾病.     

肾功能正常的抗肾小球基膜抗体相关疾病--附3例报道

目的 :了解肾功能正常的抗肾小球基膜 (GBM)抗体相关疾病的临床和病理特点。　 方法 :收集近 6年在我科确诊的 1 0 5例抗GBM抗体相关疾病患者的临床病理资料 ,对其中肾功能一直保持正常的患者重点分析 ,并应用间接免疫荧光法 (IIF)、酶联免疫吸附法 (ELISA)及免疫印迹法 (Western blotanalysis)检测及鉴定血清抗GBM抗体。　 结果 :1 0 5例患者中 3例 (2 86 % )肾功能一直保持正常 ,平均随访时间 2 2～ 57(40± 1 7 5)个月。均为青年男性。其中 2例表现为Goodpasture综合征 ,1例单纯表现为肺出血。 2例行肾活检 ,病理均为轻度系膜增生性肾小球肾炎 ,无新月体形成。直接免疫荧光和IIF均可见IgG沿肾小球毛细血管袢呈线样沉积。ELISA法检测血清抗GBM抗体均为阳性 ,Western blot法患者血清识别的蛋白条带与抗GBM抗体阳性对照一致。　 结论 :肾功能正常的抗GBM抗体相关疾病并不少见 ,我国对其认识尚不足。对有肺出血伴或不伴尿检异常的患者应考虑到该病可能 ,早期检测血清抗GBM抗体 ,可做到早期诊断 ,早期治疗。     

老年人肾小管间质性肾炎合并抗肾小球基底膜抗体阳性1例

肾小管间质性肾炎(TIN)是一种常见但易被忽视的临床病理综合征。抗肾小球基底膜(GBM)抗体阳性多见于急进性肾小球肾炎,其肾脏病理主要表现为新月体肾炎,两者均可表现为快速进展的肾功能不全,由于早期临床症状及指标变化不典型,常延误诊治甚至导致终末期肾脏病(ESRD)。现报道一例老年人抗GBM抗体阳性TIN的诊治过程,以期...     

寡免疫复合物型急进性肾炎的诊断治疗进展

1前言急进性肾小球肾炎(rapidly progressive glomerulone-phritis,RPGN)是一组表现为血尿、蛋白尿及进行性肾功能减退的临床综合征,是肾脏科常见的急危重症,肾活检病理通常表现为新月体肾炎。根据免疫发病机制,这组严重的肾小球疾病分为3种类型:即Ⅰ型,抗肾小球基膜(GBM)肾炎,由抗GBM抗体所介导。Ⅱ型,免疫复合物(IC)肾炎,由IC所介导,其病因多样化,如狼疮性肾炎、IgA肾炎、过敏紫癜性肾炎、冷球蛋白血症等多种疾病在病理上均可表现为这类新月体肾炎。Ⅲ型,寡免疫复合物型肾炎,免疫荧光无或仅见少量免疫复合物沉积于肾小球,通常认为…     

免疫吸附治疗抗肾小球基膜抗体疾病--附5例报告

目的：探讨免疫吸附(IA)治疗对抗肾小球基膜抗体(抗—GBM)疾病患者血清抗—GBM水平的影响及其临床疗效。方法：5例抗—GBM疾病患者，4例伴有明显肺出血，1例仅有肾损害，临床均表现为急进性肾炎，SCr312—1290μmol/L。肾活检显示肾小球新月体比例26．3％—100％。血清抗-GBM抗体40．6％—203．2RU／ml。在激素治疗同时，应用葡萄球菌A蛋白吸附柱进行免疫吸附治疗，一疗程共10次，再生血浆30—60L。结果：吸附治疗10次后，3例血清抗—GBM抗体转阴，随访4个月时抗—GBM抗体仍阴性。1例吸附治疗后血清抗-GBM抗体仍阳性，但较治疗前下降62．8％，进行第二个疗程吸附后，抗—GBM抗体转阴。4例伴有肺出血患者治疗后肺出血迅速消失。4例治疗前需血液透析的患者治疗后1例摆脱透析。SCr由505μmol/L降至157μmol/L，另3例肾活检病理显示100％新月体形成者仍需维持性血液透析。1例治疗前不需血液透析者肾功能保持稳定。结论：葡萄球菌A蛋白免疫吸附能有效降低血清抗—GBM抗体水平，迅速缓解肺出血，但改善肾功能的疗效受肾脏损害程度的影响。     

人类不同类型的肾小球肾炎肾小球内IgG亚类的沉积情况

人类的肾小球肾炎肾小球内Ig及补体沉积可分别因免疫复合物介导或抗肾小球基底膜(glomerularbasement membrane,GBM)介导而呈颗粒形或线形。虽然在各型肾炎IgG的沉积情况已有许多报道,但对4种重链IgG亚类在肾炎患者的肾小球内沉积情况尚无深入研究。作者对28例不同类型肾炎病人的肾标本,除常规用直接免疫荧光观察IgG、IgA、IgM、Clq、C3、纤维蛋白原及α2巨球蛋白的沉积情况外,还用间接免疫荧光技术对IgG亚类的沉积情况进行了观察。28     

抗肾小球基膜抗体疾病的临床流行病学分析(附14例报告)

目的通过对抗肾小球基膜抗体疾病(抗-GBM疾病)病例的回顾性分析,为我国抗-GBM疾病的流行病学、临床及病理表现特征、治疗现状及预后等方面提供更多资料.方法回顾性分析本所肾脏病临床中心在1980～2000年间14例经肾活检证实诊断为抗肾小球基膜抗体疾病患者的临床病理资料.结果该14例抗-GBM疾病患者占全部自体肾肾活检病例的0.14%,占新月体肾炎的9.1%.14例患者中男性13例,女性1例,平均起病年龄为(26.7±8.1)岁,大多患者在冬春季节起病,10例于发病前一月内有呼吸道感染史.14例患者均在起病时或短期内出现急进性肾功能衰竭,13例需肾脏替代治疗;8例病程中出现咯血,其中6例以咯血起病;全部病例均伴有不同程度的贫血;1例患者伴有中枢神经系统受累.肾脏受累主要表现为肉眼血尿(8/14)、少尿(10/14)或无尿性肾功能衰竭(3/14).起病时血清学检查抗-GBM抗体(间接免疫荧光法)阳性者13例(另一例在病程后期出现阳性),血清C3水平均正常,抗核抗体、抗双链DNA抗体及抗中性粒细胞胞浆抗体均阴性.病理上均出现大量新月体形成,其中13/14表现为新月体肾炎(新月体比例＞50%),8/14表现为100%的新月体肾炎,4例出现明显血管袢坏死改变.免疫荧光检查均有沿毛细血管袢基膜弥漫沉积的线状免疫复合物,均为IgG类抗体介导的免疫沉积物,1例同时伴有IgA的沉积.2例重复肾活检提示在短期内细胞性新月体即转化为纤维细胞性新月体和纤维素性新月体,并且出现肾小球全球硬化及小管间质的慢性化改变.早期应用血浆置换疗法及甲基强的松龙冲击治疗能有效缓解肺出血,并可能改善肾功能衰竭.随访表明,全部患者均需采取长期肾脏替代治疗,2例肺部出血反复发作,对再次甲基强的松龙冲击治疗仍有良好反应.结论本文报道的14例抗-GBM疾病患者初步反映了中国人抗-GBM疾病的临床流行病学特征.     

血清抗中性粒细胞胞浆抗体阳性的抗肾小球基膜肾炎的临床与病理特征

目的：回顾性分析血清抗中性粒细胞胞浆抗体(ANCA)阳性抗肾小球基膜(GBM)肾炎的临床和病理特征。方法：对解放军肾脏病研究所1994年至2002年住院确诊抗GBM肾炎的23例患者进行血清ANCA检测，对其中11例ANCA阳性患者在流行病学、临床及病理等方面进行分析，并与血清ANCA阴性抗GBM肾炎及ANCA相关性寡免疫复合物型新月体肾炎患者进行比较。结果：23例抗GBM肾炎患者有11例(47．8％)同时存在血清ANCA阳性。其中髓过氧化物酶-ANCA(MPO-ANCA)阳性者4例(36．4％)，蛋白酶3-ANCA(PR3-ANCA)阳性者1例[9．09％，该例同时合并MPO-ANCA及胞浆型ANCA(C-ANCA阳性)]，核周型(P-ANCA)阳性者3例(27．3％)，DANCA阳性者5例(45．5％)。血清ANCA阳性和阴性抗GBM肾炎患者在流行病学、临床表现、病理改变及预后等方面无差异，二者与ANCA相关性寡免疫复合物型新月体肾炎患者相比，在发病年龄、性别比例、少尿(无尿)及就诊时终末期肾衰发生率、新月体性质、肾小球硬化、肾间质小血管病变及预后等方面差异显著。血清ANCA阳性和阴性抗GBM肾炎患者对治疗的反应和预后均很差，ANCA相关性寡免疫复合物型新月体肾炎患者预后相对较好。结论：血清ANCA阳性和阴性的抗GBM新月体肾炎可能为同源性疾病，而ANCA相关性寡免疫复合物型新月体肾炎与之不同。     

肺出血肾炎综合征

肺出血肾炎综合征(Goodpasture's syn-drome,GPS)是一种病因尚未明了的少见病。除有肺出血及肾小球肾炎的临床表现外,血清中可检出循环抗肾小球基底膜(抗-GBM)抗体,免疫荧光检查可见 IgG 沿 GBM 和肺泡基底膜呈线状沉积。本病在1919年由 Good-pasture 首先描述而得名。此后,世界各地报告的病例数渐增,1970年 Proskey 统计已超过100例。关于 GPS 患者肺、肾受累的先后问题,     

A case of Goodpasture's syndrome associated with anti-myeloperoxidase antibodies.

A case of Goodpasture's syndrome with anti-myeloperoxidase (MPO) antibodies is reported. Histological examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular capillary walls and alveolar capillary walls by immunofluorescence microscopy. Not only anti-glomerular basement membrane (GBM) antibodies but also anti-MPO antibodies, an anti-neutrophil cytoplasmic antibody, were simultaneously detected in the serum. Although it is generally accepted that crescentic glomerulonephritis in Goodpasture's syndrome is mediated by anti-GBM antibodies, this case suggested that anti-MPO antibodies might also participate in the pathogenesis of crescentic glomerulonephritis and probably alveolar hemorrhage of Goodpasture's syndrome, especially with vasculitis.     

An autopsy case of Goodpasture's syndrome with P-ANCA and systemic vasculitis]

A 72-year-old woman was admitted because of anorexia and dyspnea. She was given a diagnosis of pulmonary hemorrhage and renal failure. Despite treatment with high-dose steroid and hemodialysis, the patient died of disseminated intravascular coagulation on the 9th hospital day. Autopsy revealed intra-alveolar hemorrhage, crescentic glomerulonephritis, and systemic vasculitis with fibrinoid necrosis. A direct immunofluorescence study demonstrated linear deposition of IgG along the glomerular basement membrane (GBM). Both anti-GBM antibody and anti-neutrophil cytoplasmic antibody with perinuclear pattern (P-ANCA) were detected in the patient's serum by enzyme immunoassay. Goodpasture's syndrome with P-ANCA was diagnosed. There has been some controversy as to whether vasculitis occurs in patients with Goodpasture's syndrome. This was a rare example of well-documented Goodpasture's syndrome with P-ANCA and systemic vasculitis, the exact etiologic relationships among which remain to be clarified.     

Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody

A subset of patients with crescentic glomerulonephritis (CGN) is characterized serologically by the presence of antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti-GBM) called “double positive” disease. The clinical significance of the occurrence of both antibodies is not clear. This study aims to describe the clinical and histologic characteristics and outcomes of CGN in a US cohort of double positive (DP) patients and compare them to patients with anti-GBM disease only or ANCA only (ANCA-associated vasculitis (AAV)). Renal biopsies with a diagnosis of CGN with either pauci-immune or linear immunofluorescence were selected and classified as AAV, anti-GBM disease, or DP based on serologic testing at the time of biopsy. Data on demographics, clinical presentation, treatment, and outcome were obtained by chart review. Six patients with anti-GBM disease, 9 with DP disease, and 18 AAV patients matched for year of diagnosis with DP were identified. Extrarenal disease manifestations were more prominent in the DP patients. The DP patients had severe renal dysfunction at presentation with eight of nine patients requiring dialysis at presentation. Renal biopsy findings of DP patients were similar to anti-GBM disease with majority of glomeruli showing cellular crescents. Eighty-nine percent of patients were treated with immunosuppressive therapy and 78 % with plasmapheresis. At 1 year, all nine DP patients reached end-stage renal disease. We conclude that the DP patients share extrarenal manifestations similar to AAV patients while the renal manifestations resemble anti-GBM patients clinically and histologically. The renal prognosis of DP patients remains poor despite treatment.     

Anti-glomerular basement membrane antibody disease with granulomatous lesions on renal biopsy

We present the case of a 56-year-old woman with anti-glomerular basement membrane (anti-GBM) antibody disease accompanied by granulomatous reaction in the kidney. Three months prior to admission to our kidney center, she had suffered from interstitial pneumonia and had a slightly elevated level of MPO-ANCA (13 EU). Her serum level of creatinine was normal (0.72 mg/dl) but proteinuria (1+) and hematuria (2+, 1-4/HF) were present. She was admitted to our hospital because of general fatigue, loss of appetite, high fever (over 38.5 degrees C) and a rapid decline in renal function (creatinine 8.50 mg/dl). Hemodialysis therapy was started immediately after admission. The serological study was negative for MPO-ANCA and PR3-ANCA but positive for anti-GBM antibody (139 EU). Renal biopsy demonstrated necrotizing glomeruli, cellular crescents and grauloma formation with multinucleated giant cells. Immunofluorescence microscopy revealed linear staining of IgG and C3. We diagnosed graulomatous, crescentic and necrotizing glomerulonephritis, patho-logically. She was diagnosed as having anti-GBM antibody disease because alveolar hemorrhage was absent. Steroid therapy including methylprednisolone pulse therapy (500 mg/day, 3 days) and 2 courses of plasma exchange were effective in reducing the fever, anti-GBM antibody titer and C-reactive protein level. Her renal function recovered and she was able to quit hemodialysis therapy 68 days after the start of hemodialysis and she has shown no signs of pulmonary alveolar hemorrhage to date. The present case suggests that intensive therapy may restore renal function in anti-GBM disease even though renal function was sufficiently damaged and required hemodialysis therapy and active pathological changes were observed in renal biopsy specimens.     

The appearance of nonlinear deposits of immunoglobulins in Goodpasture's syndrome

A twenty year old woman presented with pulmonary hemorrhage and glomerulonephritis with linear deposition of IgG on the glomerular capillary basement membrane, and high titer of antiglomerular basement membrane antibody in her serum. Without treatment, renal function, which was transiently impaired, has improved, pulmonary hemorrhage subsided, and repeat renal biopsies have revealed the appearance of nonlinear in addition to the linear deposition of IgG on the glomerular capillary basement membrane in the face of diminished serum antiglomerular basement membrane antibody titer.     

抗肾小球基膜抗体疾病的临床及病理分析

７例抗肾小球基膜抗体疾病占全部肾活检病例的０．１４％，男女比为６∶１，平均起病年龄２６．１±７．６岁。其临床表现为前驱性呼吸道病毒感好（５／７），肺出血（５／７），肾脏受累（７／７），高血压（７／７），中重度贫血（７／７）及中枢神经系统受累（１／７）。肾脏受累表现为镜下血尿或肉眼血尿（７／７）、中度蛋白尿（６／７）及急进性肾功能减退（７／７）；肾脏病理改变的特征为新月体形成及线状ＩｇＧ沉积物沿毛细血管袢基膜弥漫沉积，伴突出的间质改变。重复肾活检早期有效的治疗可显著减少新月体形成的肾小球比例及细胞性新月体比例，同时细胞性新月体可在短期内向纤维细胞性新月体或纤维素性新月体转化，使肾小球发生球性硬化。早期血浆置换及甲基强的松龙冲击治疗可缓解肺、肾损害，而缓解后停用免疫抑制治疗则可能导致复发。     

FIBRILLARY GLOMERULONEPHRITIS – A REPORT OF TWO CASES

Two patients with an uncommon form of glomerulonephritis are described. The main clinical features were hematuria and proteinuria associated with normal renal function. The glomerular lesions consisted of mesangial hypercellularity and capillary wall thickening. Immunofluorescence was positive for IgG and C3 in both cases. Widespread deposition of microfibrils (mean diameters 17.0 nm and 18.4 nm) within mesangial areas and capillary basement membranes was seen on electron microscopy. Congo red staining for amyloid was negative. In both patients there was no evidence of underlying disease or extra-glomerular involvement and hence the disorder appeared to represent a primary glomerulonephritis.     

Membranous glomerulopathy induced by myeloperoxidase-anti-neutrophil cytoplasmic antibody-related crescentic glomerulonephritis

A 68-year-old woman was referred for evaluation of nephrotic-range proteinuria and a course suggesting rapidly progressive glomerulonephritis. Serum anti-neutrophil cytoplasmic antibody against myeloperoxidase (MPO) was 204 U/ml. A renal biopsy specimen revealed necrotizing glomerulonephritis with crescent formation. However, immunofluorescence showed staining with IgG and C3 along capillary walls. IgG positivity included both IgG1 and IgG4. Electron microscopic examination disclosed both paramesangial and subepithelial deposits. This case suggests that rarely, MPO-ANCA-related crescentic glomerulonephritis may present nephrotic-range proteinuria and show immune deposits along capillary walls.     

丙基硫氧嘧啶导致的抗中性粒细胞胞质抗体阳性小血管炎及其靶抗原研究

目的 研究丙基硫氧嘧啶（PTU）引起的抗中性粒细胞胞质抗体（ANCA）阳性小血管炎的临床病理表现及其靶抗原。方法 对我院近年诊治的4例PTU引起的ANCA阳性小血管炎患者进行临床病理分析。以纯化的7种已知的ANCA靶抗原蛋白酶3（PR3）、髓过氧化物酶（MPO）、人白细胞弹力蛋白酶（HLE）、乳铁蛋白（LF）、组蛋白酶G（CG）、杀菌／通透性增高蛋白（BPI）和天青杀素（AZU）为固相抗原,采用ELISA法检测患者血清的靶抗原及治疗前后抗体滴度的变化。结果 4例病人中男女各2例,平均年龄30（11－57）岁,服PTU时间7－60个月。4例均有肾脏、肺脏、皮肤、关节肌肉和血液系统等受累,均为p-ANCA阳性,患者血清均识别MPO、LF和CG;3例识别HLE、AZU,2例识别PR3;无1例识别BPI。多数抗体滴度高,可大于1：25600;而服PTU无小血管炎临床表现的甲状腺功能亢进（甲亢）病人的30份血清均为阴性。肾活检2例为新月体性肾炎,2例为轻微病变,免疫荧光检查均为阴性。4例患者均立即停用PTU,3例应用免疫抑制剂,1例行血浆置换。4例小血管炎的临床症状均得以缓解,但1例晚期新月体肾炎患者发展为慢性肾衰竭而依赖透析。停药和治疗后各种抗体滴度均有所下降,但多未能短期阴转。结论 PTU可引起ANCA阳性小血管炎,其自身抗体可识别中性粒细胞胞质中多种已知的靶抗原;及时诊治,预后较好。     

Diffuse intrapulmonary hemorrhage and glomerulonephritis unrelated to anti-glomerular basement membrane antibody

Nine patients with diffuse intrapulmonary hemorrhage and glomerulonephritis not due to anti-glomerular basement membrane (anti-GBM) antibody are described and similar previously reported cases are reviewed. Eight patients were seen during a four-year interval and represented 47 percent of the cases of pulmonary hemorrhage and glomerulonephritis seen during this period. Diagnoses included systemic vasculitis of unspecified type in two patients with seropositive rheumatoid arthritis, idiopathic crescentic glomerulonephritis with negative immunofluorescence in two, Wegener's granulomatosis in two, and polyarteritis nodosa, Henoch-Schönlein purpura, and mixed connective tissue disease in one each.Differentiation from anti-GBM antibody-mediated pulmonary hemorrhage and glomerulonephritis by clinical evaluation alone was frequently difficult, emphasizing the importance of both immunopathologic studies and evaluation of serum for anti-GBM antibody in all patients with pulmonary hemorrhage and glomerulonephritis.In eight of nine patients, significant episodes of pulmonary hemorrhage improved markedly within 24 to 72 hours following initiation of high-dose corticosteroid therapy. In contrast, renal function did not improve in the majority of patients.