儿童抗肾小球基底膜抗体伴抗中性粒细胞胞浆抗体阳性肾炎一例

我们于2005年8月收治了1例临床表现为急进性肾炎的患儿,检测Anti-GBM和ANCA均阳性,肾脏病理示新月体肾炎,现报道如下。患儿,女性,12岁,因恶心呕吐1月余,伴肾功能不全、高血压入院。在当地医院查Hb 56 g／L,RBC 1．87× 1012／L,Alb 26．2 g／L,Scr 590 μmol／L,BUN 22．12 mmol／L, 尿蛋白3+,红细胞2+。胸片示双肺水肿。经治疗无效,于 8月25日转入我院。     

感染性心内膜炎相关性肾小球肾炎伴抗中性粒细胞胞浆抗体阳性2例报告

感染性心内膜炎(infective endocarditis,IE)是不常见的心内膜表面微生物感染性疾病,其年发生率为每10万人2～10例,心脏瓣膜是最常受累及的部位^[1-2]。IE的肾脏并发症曾被认为主要是因为微生物栓子栓塞导致的肾梗死或脓肿,而现在的研究表明,超过80%的病理类型为增生性肾小球肾炎^[3-4]。肾小球肾炎多由免疫复合物所介导,免疫荧光可见系膜区及毛细血管壁免疫球蛋白(immunoglobulin,Ig)G、Ig M、补体C3沉积,可有Ig A沉积^[5]。     

丙基硫氧嘧啶致抗中性粒细胞胞浆抗体阳性新月体肾炎2例

丙基硫氧嘧啶是治疗甲状原机能亢进最常用的药物之一 ,近年来国内屡有报道该药引起血管炎性肾损害 ,现将我们收治的二例报告如下 :病　　例例 1男性 ,13岁 ,患者于 7岁时患甲状腺机能亢进即开始服用丙基硫氧嘧啶 ,每日 15 0ｍｇ ,病情稳定后减为每日10 0ｍｇ ,一直服用 6年 ,病情控制良好。 2 0 0 0年 4月初病情加重 ,遂将药量加至每日 4 5 0ｍｇ。两周后患儿足背、踝部水肿 ,双下肢小腿内外侧出现紫红色皮疹 ,给予对症治疗后好转。 1个月后出现发热 ,全程性肉眼血尿伴双下肢水肿 ,遂收治入院。查体 :急性病客 ,贫血貌 ,面色苍白 ,精神萎靡 …     

抗中性粒细胞胞浆抗体相关性肾炎伴显著IgA沉积一例

患者：女性，54岁，因间断肉眼血尿半年，伴肾功能不全2个月，于2003年10月30日入院。患者于6个月前出现洗肉水样尿3次，尿中未发现凝血块，伴尿频，无尿急、尿痛；无发热、腰痛，无尿少、颜面下肢浮肿；院外查“尿Pro( )，BLD( )，血Hb92g／L，肾功能正常”，抗感染治疗后肉眼血尿消失，未行尿复查。2个月前又出现洗肉水样尿，伴低热(体温不详)；查尿Pro(     

原发性干燥综合征合并抗肾小球基底膜新月体肾炎一例

现报道1例原发性干燥综合征伴抗肾小球基底膜型新月体肾炎。患者,女,70岁,因眼干、口干、四肢肌痛1年,咳嗽发热2周,少尿伴血肌酐升高1周入院。患者1年前于当地医院查RF 397 U／ml,ANA 1:320,CRP 5 ,ESR 34 mm／h, at-SM(-),at-SSA(-),at-SSB(-),角膜荧光( ),腮腺造影及唇黏膜活检(唇腺病理:小唾液腺组织见灶性间质细胞淋巴浆细胞浸润,50个／HPF),支持干燥综合征诊断。 2周前元明显诱因出现发热38．9℃,畏寒,伴咳嗽、咳痰。     

丙基硫氧嘧啶致抗中性粒细胞胞浆抗体阳性小血管炎一例报告

近年来,国内外陆续报道甲亢患者服用丙基硫氧嘧啶（PTU）可以引起抗中性粒细胞胞浆抗体（ANCA）阳性小血管炎（MPA）,笔者曾诊治1例,现报告如下。     

抗肾小球基底膜肾炎的发病机制

抗肾小球基底膜（glomerular basement mem brane,GBM）病是循环中的抗GBM抗体在组织中沉积所引起的一组自身免疫性疾病。肺、肾为主要受累的器官,如病变局限在肾脏称为抗GBM肾小球肾炎;当肺肾同时受累时称为Goodpasture综合征。临床可表现为肺出血和／或急进性新月体肾炎。多数患者起病急、病情进展快、预后差,急性肾衰竭是本病的主要死亡原因。     

抗肾小球基底膜肾炎的治疗

抗基底膜肾炎（抗GBM肾炎）是一种罕见的、具有特征性病因的肾小球肾炎,患者体内存在特异性针对肾小球和／或肺基底膜内抗原的自身抗体。这些自身抗体与基底膜Ⅳ型胶原α3链特异结合后病情进行性发展,肾功能常在几天或几周内进入肾衰竭阶段。若无恰当的治疗,死亡率高达90％以上,少数患者早期即死于肺大出血。20世纪90年代后,随着对抗GBM肾炎的病因和发病机制进一步深入的认识,加上血浆置换、     

Analysis of clinical features and prognosis of anti-glomerular basement membrane antibody positive patients with anti-neutrophil cytoplasmic antibodies

Objective To investigate the characteristics and outcome of glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody. Methods The sera of 23 anti-GBM glomerulonephritis patients were collected and were tested for ANCA respectively. Characteristics and outcome of patients with coexisting anti-GBM antibody and ANCA were analyzed, and were compared with anti-GBM glomerulonephritis patients without coexisting ANCA. Results Among the 23 sera with anti-GBM antibody, 7 sera had coexisting ANCA (7 MPO-ANCA, 1 PR3-ANCA), which represented 30.4% of the anti-GBM glomerulonephritis patients. The incidence of hemoptysis and hematuria in ANCA+-anti-GBM glomerulonephritis group was significantly higher than that in ANCA--anti-GBM glomerulonephritis group (P＜0.05). No significant difference in age, sex, other clinical manifestations and pathological features were found between patients with and without coexisting serum ANCA. Conclusion The incidence of hemoptysis and hematuria in ANCA+-anti-GBM glomerulonephritis group is significantly higher than that in ANCA--anti-GBM glomerulonephritis group, but the prognoses of the two groups were poor.     

Abnormal expression of glomerular basement membrane laminins in membranous glomerulonephritis.

BACKGROUND: Proteinuria associated with glomerular diseases is secondary to alterations of the charge-selective and/or size-selective properties of the glomerular basement membrane (GBM), but molecular alterations that are responsible for these functional changes are still poorly understood. Analysis of mice harbouring a null mutation in the gene encoding the beta 2 chain of laminin has suggested that the presence of abnormal laminin chains within the GBM can be responsible for proteinuria. METHODS: We have investigated whether abnormal laminin ss chains could be detected by immunohistochemistry within the GBM of patients with proteinuria and minimal change disease (five patients), focal and segmental glomerulosclerosis (five patients), or primary membranous glomerulonephritis (10 patients). Three patients with mesangiocapillary glomerulonephritis and three patients with IgA nephropathy were also studied as controls. RESULTS: We showed that the GBM of all 10 patients with membranous glomerulonephritis, but not of patients with other glomerulopathies, contained laminin beta 1, which is normally expressed only during metanephros development. The re-expression of the beta 1 chain of laminin was not associated with that of the embryonic alpha 1 chain of type IV collagen, or with the loss of expression of vimentin and synaptopodin, two markers of differentiated podocytes. CONCLUSIONS: The presence of new laminin isoforms within the GBM of patients with membranous glomerulonephritis could play a role in the occurrence of proteinuria, by modifying either the sieving properties of the GBM or the interactions between podocytes and the GBM.     

Report of a patient with rheumatoid arthritis developing rapidly progressive glomerulonephritis associated with anti-glomerular basement membrane antibody and antineutrophil cytoplasmic antibody

Rapidly progressive glomerulonephritis occurred in a 63-year-old woman with rheumatoid arthritis who had been treated with oral prednisolone for 5 years. Microscopic examination of the renal biopsy specimen showed marked obliteration of the tufts with noticeable cellular crescent formation in all glomeruli. Immunofluorescence staining of the biopsy specimen showed linear deposits of immunoglobulin G (IgG) diffused along the capillary walls. The serologic examination was positive for antiglomerular basement membrane antibody and perinuclear antineutrophil cytoplasmic antibody. Despite a tentative trial of plasma exchange and intensive combined therapy (intravenous administration of heparin and pulse therapy of methylprednisolone and cyclophosphamide), renal function progressively deteriorated and no recovery occurred.     

Immunoelectron microscopic study on type I, II and III TGF-beta receptors on visceral glomerular epithelial cells in relation to glomerular basement membrane alterations in proteinuric rats.

BACKGROUND: Transforming growth factor (TGF)-beta is a regulator of extracellular matrix accumulation. Both TGF-beta receptors, type I (TbetaRI) and type II (TbetaRII), may be required for signal transduction in the TGF-beta pathway. The aim of this study was to investigate the relationship between the TGF-beta pathways and glomerular basement membrane (GBM) accumulation in vivo. METHODS: We examined TbetaRI, II, and III protein expression on visceral glomerular epithelial cells (GEP) in relation to GBM alterations in passive Heymann nephritis (PHN), anti-GBM nephritis and anti-thymocyte serum (ATS) nephritis. Renal tissues were examined by pre-embedding immunoelectron microscopy 3, 7 and 14 days after induction of nephritis in rats. RESULTS: In normal control rats TbetaRI was not detected on GEP, TbetaRII expression was very occasionally found on GEP and TbetaRIII was seen in the cytoplasm of the GEP. TbetaRI, TbetaRII, and TbetaRIII were constitutively expressed on glomerular endothelial cells. By day 3 of anti-GBM nephritis and PHN, expression of TbetaRI, TbetaRII, and TbetaRIII was still similar to that of normal control rats, and GBM alterations in both models were not prominent except for deposit formation in PHN. From day 7 onwards, in both models, expression of TbetaRI and TbetaRII on GEP increased in association with GBM thickening. Expression of TbetaRIII in the cytoplasm of the GEP was increased, with occasional positive staining being seen on the urinary surface of the GEP from day 7 onwards. On the other hand, at day 3 of ATS nephritis, increased expression of TbetaRI and TbetaRII on GEP was noted, but from day 7 onwards, expression of TbetaR II on GEP dramatically decreased. Expression of TbetaRIII in the cytoplasm of the GEP also transiently increased at day 3. GBM thickening was not noted in ATS nephritis. CONCLUSIONS: The results suggest that persistent upregulation of expression of TbetaRI, TbetaRII and possibly TbetaRIII on GEP may contribute to GBM matrix accumulation in vivo.     

Unusual glomerulopathy with atypical thickening of the glomerular basement membrane and intramembranous microparticles

A 57-year-old Japanese female was admitted because of edema, hypoproteinemia and proteinuria. Her histopathological findings of renal biopsy specimen were quite unique. Light microscopic findings suggested membranous glomerulonephritis, but no significant deposition of immunoglobulins or complements was detected in glomeruli by immunofluorescence. Electron microscopic examination revealed irregular thickening of the glomerular basement membrane (GBM). The GBM had no electron-dense deposits, but numerous microparticles varying in shape and size were present in all the thickened GBM and occasionally in the mesangium. The microparticles were round or oval in shape, and the size varied widely, measuring 25–290 nm (mostly 40–120 nm). The cytoplasmic infolding into the GBM by podocytes was seen. The large-sized particles had microgranules, mimicking free ribosomes seen in podocytes or endothelial cells. We conclude that cytoplasmic infolding and subsequent degradation may, partly, contribute to the formation of microparticles in the GBM.     

Age-dependent thickening of glomerular basement membrane has no major effect on glomerular hydraulic conductivity.

BACKGROUND: The effect of the increasing thickness of the glomerular basement membrane (GBM), which is seen in ageing rats, on the effective hydraulic conductivity (k) of the glomerular capillary wall was studied in Wistar rats aged 2 and 18 months. METHODS: With the use of micropuncture techniques, ultrafiltration characteristics of cortical glomeruli were determined in isolated cell-free perfused kidneys. Because the filtration fraction in this preparation is low (3%) as a consequence of high perfusion rates at glomerular filtration rates comparable with in vivo conditions, uniform ultrafiltration conditions are provided over the whole filtering surface. After fixation at a defined perfusion pressure, the surface of glomerular capillaries (S) was obtained morphometrically on light microscopic sections of the glomeruli studied previously. RESULTS: The glomerular ultrafiltration coefficient (K(f)) was 0.025 nl/s.mmHg in young rats and 0.038 nl/s.mmHg in old rats (P<0.0005) and S was 0.140 mm(2) in young and 0.244 mm(2) in old rats (P<0.0005). However, k was not significantly different (18.0 nl/s.mmHg.cm(2) in young and 15.8 nl/s.mmHg.cm(2) in old rats) despite a 2.4-fold increase of GBM thickness as estimated from electron microscopic sections. CONCLUSIONS: These findings indicate that the age-dependent increase of GBM thickness in rat kidneys did not substantially increase hydraulic resistance of the glomerular capillary wall.     

100例新月体肾炎的免疫病理分型及临床病理分析

目的：了解新月体性肾炎的免疫病理分型及其临床病理特点。方法：对我科近10年来经肾活检确诊的100例新月体性肾炎进行回顾性分析,对患者血清进行抗中性粒细胞胞浆抗体（ANCA）和抗肾小球基底膜（GBM）抗体的检测。结果：100例患者中21％为抗GBM抗体型,其中6／21例同时合并ANCA阳性;47％为免疫复合物型,其中9／47型ANCA阳性;32％为少免疫沉积型,其中17／32例为ANCA阳性小血管炎。3种类型相比,抗GBM抗体型以青年男性为主,多有少尿或无尿（P＜0．05）,肾小球受累受为广泛（P＜0．001）,预后差（P＜0．001）。免疫复合物型以中青年为主,多表现为肾病综合征（P＜0．01）,强化免疫抑制治疗有效。少免疫沉积型以中老年为主,有多系统受累（P＜0．05）,治疗效果相对较好。结论：我国新月体肾炎中虽仍以免疫复合物型为主,但抗GBM抗体型和ANCA阳性小血管炎并不少见。肾活检免疫病理和血清自身抗体的联合应用对新月体肾炎进行分类更接近病因学诊断。     

Aberrant proteoglycan composition of the glomerular basement membrane in a patient with Denys-Drash syndrome

BACKGROUND: To ascertain whether changes in proteo-glycans are involvedin the pathogenesis of the nephrotic syndrome in Denys—Drashsyndrome (DDS), we analysed the glycosaminoglycan (GAG) contentand composition of the glomerular basement membrane (GBM) inone child with this disorder and in children of comparable agewho had died from unrelated disorders. METHODS: The diagnosis of DDS was confirmed by the presence of a previouslydescribed mutation in the WT1 gene (a tumour suppressor gene).The GAG content and composition of the GBM and tubular basementmembrane (TBM), both in the Denys-Drash patient as well as age-matchedcontrol infants, was analysed by biochemical studies and indirectimmuno-fiuorescence studies. Finally we investigated the urinaryGAG excretion of the Drash patient. RESULTS: The biochemical studies revealed that the total GAG contentin the GBM as well as TBM was comparable in the Drash patientand the control group. However, the GAG composition of the GBMof the patient was clearly different, with relatively more chondroitinsulphate. The urinary GAG content (expressed as mg GAG/mmolcreatinine) was elevated in the Denys—Drash patient dueto an increased heparan sulphate (HS(GAG)) excretion. Indirectimmunofluo-rescence (IF) studies for the core protein of humanGBM heparan sulphate proteoglycan (HSPG) showed a similar linearstaining of all renal basement membranes in the patient andthe controls. A monoclonal antibody directed against the HSchain of HSPG (MoAb 403) displayed a strong GBM and a weak TBMstaining of normal kidneys. Kidney tissue from the Drash patientdisplayed a reduced staining of the GBM with MoAb 403. IF studiesfor chondroitin sulphate proteoglycan (CSPG) showed increasedstaining of the mesangium and glomerular capillary loops inthe Denys—Drash patient which is in agreement with thebiochemical studies. No discernible differences in distributionor quality of staining with antibodies against collagen typeIV and laminin were observed. CONCLUSIONS: These biochemical and immunohisto-chemical results indicatethat in our patient the proteoglycan composition of the GBMis altered. This alteration may play a role in the pathogenesisof proteinuria in this syndrome.     

Expression of glomerular heparan sulphate domains in murine and human lupus nephritis.

BACKGROUND: Recently, we identified specific N- and 6-O-sulphated heparan sulphate (HS) domains on activated glomerular endothelial cells. In this study, we evaluated in lupus nephritis the expression of different HS domains on glomerular endothelium and in the glomerular basement membrane (GBM). METHODS: The expression of specific glomerular HS domains and the presence of immunoglobulins (Ig) were determined by immunofluorescence staining of kidney sections of patients with nephritis due to systemic lupus erythematosus (SLE) and MRL/lpr lupus mice. The expression/presence of glomerular HS domains and Ig was also evaluated after eluting Ig from renal sections of lupus mice using two elution methods, and in renal sections of lupus mice treated with heparinoids. RESULTS: Both MRL/lpr mice and patients with lupus nephritis showed a decreased expression of HS in the GBM. The expression of N- and 6-O-sulphated HS domains on glomerular endothelium was decreased in MRL/lpr mice, but increased in SLE patients. MRL/lpr mice had more extensive glomerular Ig deposits than SLE patients. After elution of Ig, the glomerular endothelial expression of N- and 6-O-sulphated HS domains in MRL/lpr mice was recovered and even increased above normal levels, while the expression of HS in the GBM was restored to normal levels. Treatment with heparinoids prevented Ig deposition and preserved the expression of glomerular HS domains at normal levels in lupus mice. CONCLUSION: The expression of specific HS domains on glomerular endothelium and in the GBM is changed during lupus nephritis due to masking by Ig deposits and induction of inflammatory N- and 6-O-sulphated HS domains.     

Knockout of aminopeptidase A in mice causes functional alterations and morphological glomerular basement membrane changes in the kidneys

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