原发性毛细血管内皮病一例

肾脏毛细血管内皮病(endotheliosis)是一种以肾小球毛细血管内皮细胞损伤为主要表现的疾病,其组织病理学特征为肾小球毛细血管内皮细胞肿胀、管腔狭窄伴肾小球体积增大.免疫荧光(IF)常表现为阴性.电镜(EM)检查示肾小球毛细血管内皮细胞弥漫增生,增生肿胀的内皮细胞充塞于毛细血管腔.肾小球内无电子致密物.这一疾病常见于血栓性微血管病,但其他疾病也可引起毛细血管内皮细胞增生和肿胀.目前尚未检索到国内有关原发性毛细血管内皮病的报道,现将我科遇见的1例报告如下.     

有毛细血管内增生的致密物沉积病一例

致密物沉积病（dense deposit disease DDD）在国内少见,而有毛细血管内增生的DDD更少见,后者与急性肾炎的病理相似,如可有肾小球毛细血管内皮细胞增生、多形核白细胞浸润和上皮下驼峰样电子致密物等,但性质及治疗不同,因此需鉴别。另外,有报道急性肾炎可转变成DDD,这就使有毛细血管内增生特点的DDD的诊断问题变得更为复杂。现报告一例表现独特的DDD并结合文献进行分析。     

肾脏淀粉样变性的临床病理分析

目的：探讨肾脏淀粉样变性病（amyloidosis,AL）的临床病理特点、诊断及鉴别诊断。方法回顾性分析9例肾脏淀粉样变性病患者的临床表现,并对其肾活检组织进行光镜、特殊染色、免疫荧光、免疫组化及超微结构观察。同时对患者进行随访获取预后信息。结果9例肾脏淀粉样变性病患者的临床上主要表现为肾病综合征伴进行性肾功能不全并逐渐恶化。肾活检组织光镜观察,早期淀粉样变光镜表现轻微,可有系膜轻度增生或基底膜空泡变性及轻度增厚,PASM染色可见节段性睫毛状结构;后期,肾小球系膜区明显增宽、基底膜增厚,毛细血管腔闭塞,呈无细胞结节硬化状态。免疫荧光表现不一,部分病例全部阴性,部分表现免疫球蛋白及补体沿系膜区或毛细血管壁不同程度的沉积。刚果红染色呈砖红色,甲基紫染色呈紫红色。免疫组化显示,5例来源于轻链λ,1例来源于轻链κ,全阴性者有3例。电镜观察下,肾小球毛细血管基底膜部分节段无明显病变,部分节段不规则增厚,肾小球基底膜外侧和（或）内皮下可见淀粉样纤维沉积;系膜轻、中度无细胞性增生,其内可见不规则排列淀粉样纤维沉积,直径8~10 nm,无分支,僵硬,排列紊乱。足突大部分融合,肾间质纤维化,其内亦可见淀粉样纤维沉积。结论肾脏淀粉样变性多见于中老年,根据光镜的典型病理学改变,并结合刚果红和甲基紫染色,可明确诊断。电镜检查是早期诊断肾淀粉样变的重要手段。     

水痘带状疱疹病毒相关性肾小球肾炎及脑炎一例报告及文献复习

目的 介绍1例水痘带状疱疹病毒相关性肾小球肾炎及脑炎病例。 方法 分析患者临床和肾脏病理资料,并复习有关文献。 结果 男性15岁患者,水痘发病后5 d出现急性肾炎综合征、肾病综合征表现及肾功能损害,血清补体C3下降。肾组织光镜检查诊断为毛细血管内增生性肾小球肾炎,伴足细胞增生及重度肾小管损伤;免疫荧光检查显示“满堂亮”;电镜检查见到多部位电子致密物。另外,电镜及Mann染色光镜检查还见到病毒样颗粒或（和）包涵体。血清病毒学检查水痘带状疱疹病毒（VZV）IgM抗体阳性。肾组织免疫组化染色和原位杂交显示肾小球及肾小管上皮细胞内存在VZV抗原及转录产物RNA。病程中患者曾多次出现癫痫发作,头颅磁共振检查及脑电图表现符合病毒性脑炎继发癫痫。所以本病例水痘-带状疱疹病毒相关肾炎及脑炎诊断成立。 结论 通过血清病毒学及组织病毒学多项检查证实本例为水痘-带状疱疹病毒相关性肾炎及脑炎,是首例报道。     

慢性乙型肝炎合并淀粉样变性肾病1例报道与分析

目的 探讨淀粉样变性肾病的病理学特点,为临床诊断提供依据. 方法 对本院1例慢性乙肝合并淀粉样变性肾病患者的病例资料,如血常规、尿常规、生化、肾脏穿刺病理等结果进行回顾性分析总结. 结果 本例病理诊断为淀粉样变性肾病,AA型.光镜下系膜区可见团块状均质无结构物质沉积,管壁可见均质物质沉积;电镜下肾小球系膜细胞和血管壁无细胞性增宽伴淀粉样细纤维结构分布,上皮足突节段融合;刚果红染色肾小球系膜区以及血管壁沉积的团块样物质呈砖红色,在偏光下呈苹果绿双折光,肾间质无明显病变;免疫荧光IgM沿系膜区和毛细血管袢弥漫颗粒状沉积,荧光强度+++;IgG、IgA、C3、C1q沿系膜区和毛细血管袢弥漫性颗粒状沉积,荧光强度++,C4沿系膜区和毛细血管袢弥漫性颗粒状沉积,荧光强度+. 结论 本病例诊断为慢性乙型病毒肝炎合并继发性肾脏淀粉样变性,淀粉样变性肾病病理特征明确;本例是否为HBV感染后发生的肾淀粉样变性以及相关机制需要复查肾组织乙肝免疫荧光、或者行原位杂交检测肾组织内乙肝病毒DNA.     

猪肾小球内皮细胞与系膜细胞的发育过程及相互关系

目的:明确中国实验用小型猪肾小球内皮细胞与系膜细胞的发育过程及相互关系。方法:采集不同时间点(胚胎28～112d及出生后1d、7d、14d、21d)中国实验用小型猪肾组织,应用免疫荧光技术检测胚肾发育不同阶段(帽状间充质、肾小囊体、逗号形体、"S"形体、毛细血管袢期肾小球及成熟肾小球)内皮细胞标志物CD31与系膜细胞标志物α-SMA的表达情况。结果:内皮细胞标志物CD31在胚肾早期呈散在性分布,继而围绕肾小囊体和逗号形体呈"环抱"状分布,然后进入"S"形体下端的血管裂隙内聚集形成无管腔的"前毛细血管束",最后表达于成熟肾小球毛细血管内皮细胞。系膜细胞标志物α-SMA在早期胚肾、肾小囊体和逗号形体阶段均无表达;"S"形体早期分布于"S"形体周围,后期进入"S"形体下端的血管裂隙;毛细血管袢期聚集在肾小球血管极根部;随着肾小球发育逐渐向肾小球内延伸,最终表达于成熟肾小球系膜区。CD31与α-SMA双重染色的结果显示,在毛细血管袢期CD31阳性的内皮细胞聚集形成无管腔的前毛细血管束,而α-SMA阳性的系膜细胞聚集在肾小球血管极的根部;随着肾小球发育,α-SMA阳性的系膜细胞逐渐由血管极根部向肾小球内迁移,同时CD31阳性的内皮细胞逐渐形成带有管腔的毛细血管丛。结论:中国实验用小型猪肾小球内皮细胞的发育开始于后肾间充质阶段,系膜细胞的发育开始于"S"形体阶段,即肾小球系膜细胞发育在内皮细胞之后;在肾小球血管丛形成过程中,内皮细胞与系膜细胞间可能存在重要的相互作用。     

脂蛋白肾病发病机制研究进展

脂蛋白肾病( lipoprotein glomerulopathy, LPG)是近二十余年来新发现的一种脂质沉积于肾小球,伴有类似于III型高脂血症的血脂水平异常,并终将会进展至终末期肾脏疾病（end-stage renal disease, ESRD）的肾小球疾病。其病理特征为肾小球毛细血管呈瘤样扩张,腔内充满脂蛋白血栓样物质,目前本病诊断必须依赖于肾活检穿刺病理学检查。因漏诊率高,截止目前全球报道病例数尚不足100例,而且有关发病机制的认识尚不十分明确。近年来研究普遍认为载脂蛋白E(Apolipoprotein E,ApoE)基因变异在LPG发病中起着重要的作用,脂质代谢异常、氧化应激、肾脏原位机制也参与该病的发生发展。本文通过温习其流行病学、临床表现及病理特征、实验室检查特点,重点探讨其发病机制。     

膜增生性肾小球肾炎的分类及发病机制研究进展

膜增生性肾小球肾炎（membranoproliferative glomerulonephritis,MPGN）是根据肾活检病理学特点定义的一种肾小球损伤的病理模式,其典型的病理学改变为肾小球系膜细胞和基质的增生,毛细血管壁的重构（系膜组织的插入和基底膜“双轨征”形成）,肾小球毛细血管襻呈分叶状改变。临床上,由于多种病因,通过不同的病理生理学机制均可导致MPGN样的病理损害。因此,MPGN并非一个最终的诊断,尚需临床医生积极寻找潜在的病因,探索可能的发病机制,进而进行针对性的治疗。     

急性感染后IgA为主型肾小球肾炎一例

急性感染后肾小球肾炎(APGN),即毛细血管内增生性肾小球肾炎,是一类主要与A群乙型溶血性链球菌等感染密切相关的肾小球肾炎.其组织病理学特点表现为肾小球毛细血管内增生,伴中性粒细胞浸润;免疫荧光(IF)检查显示IgC和(或)C3在肾小球内沉积;电镜(EM)检查示肾小球上皮下"驼峰"样电子致密物沉积.而以肾小球IgA沉积为突出表现的APGN较为罕见[1].近年来,一种被命名为"IgA为主型APGN(IgA-dominant APGN)"陆续有文献报道[2-6].近期我们遇见1例,报告如下.     

银屑病合并IgA或非IgA系膜增生性肾小球肾炎六例临床病理分析

目的分析银屑病合并肾损害的临床病理特点。方法回顾性分析北京协和医院1983年至2004年有肾活检结果的银屑病并肾损害患者6例，分析其临床及病理特点。结果男性2例，女性4例，平均年龄38岁。肾损害在银屑病发病后平均16年(7—30年)被发现。2例表现为无症状性镜下血尿和蛋白尿；3例表现为慢性肾炎综合征；1例为肾病综合征。6例均有中大量镜下血尿，其中2例有发作性肉眼血尿：蛋白尿平均为2．05g／24h(0．01—5．42g／24h)；血压4例正常，2例升高；Scr均正常。肾组织免疫荧光检查发现系膜区IgA沉积4例，系膜区IgG沉积1例，免疫荧光阴性1例。光镜表现均不严重，轻度系膜增生3例，中度系膜增生3例；均无新月体形成；慢性肾小管间质病变不明显；2例肾内动脉内膜增生、管腔狭窄。结论在银屑病合并肾损害中，系膜增生性。肾小球肾炎并不少见。可能与银屑病存在一定关系。     

Fibrillary glomerulonephritis and immunotactoid (microtubular) glomerulopathy are associated with distinct immunologic features

BACKGROUND: The clinical relevance of distinguishing two types of glomerulonephritis (GN) with non-amyloid organized immunoglobulin (Ig) deposits-fibrillary GN (FGN) and immunotactoid (microtubular) GN (IT/MTGN)-on the basis of ultrastructural organization, is debated. METHODS: Twenty-three patients with organized glomerular Ig deposits were classified into two groups based on the fibrillar or microtubular ultrastructural appearance of the deposits. Kidney biopsy samples were studied by immunofluorescence microscopy, using anti-light chain conjugates (all cases) and anti-IgG subclass conjugates (13 patients). In each group, we studied clinicopathological features, associated monoclonal gammapathy (detected by immunoelectrophoresis and/or immunoblot) or B-cell lymphoproliferative disease, effects of chemotherapy and long-term renal outcome. RESULTS: In 14 IT/MTGN and 9 FGN patients, clinical symptoms [hypertension, nephrotic syndrome (NS) and hematuria] and the mean diameters of the substructures were similar. In 13 IT/MTGN patients, glomerular (IgG1, 2 or 3) deposits were monotypic (kappa, 7 cases; lambda, 6 cases). Glomerular deposits were associated with a monoclonal Ig of the same isotype in eight patients, detected in the serum (5 cases), and/or in the cytoplasm of lymphocytes (4 cases), and with lymphoproliferative disease in seven patients. The ultrastructural features of monoclonal Ig inclusions in lymphocytes were similar to those of glomerular microtubular deposits. In contrast, none of the FGN patients presented lymphoplasmocytic proliferation or paraproteinemia. Glomerular Ig deposits were polyclonal in eight cases and contained IgG4 in all three cases studied. Although patient and renal survival did not differ significantly between the two groups, chemotherapy led to remission of NS in ten IT/MTGN patients, with parallel improvement in hematological parameters. CONCLUSIONS: The identification of ultrastructural patterns in these nephropathies is important. GN with organized microtubular monoclonal deposits (GOMMID) probably accounts for a large proportion of immunotactoid (microtubular) GN cases.     

Proliferative glomerulonephritis with monoclonal IgG deposits: a distinct entity mimicking immune-complex glomerulonephritis

BACKGROUND: Renal disease related to the deposition of monoclonal immunoglobulins containing both heavy and light chains can occur in type 1 cryoglobulinemia, Randall type light and heavy chain deposition disease (LHCDD), and immunotactoid glomerulonephritis. We report a novel phenotype of glomerular injury that does not conform to any of the previously described patterns of glomerular involvement by monoclonal gammopathy. METHODS: Ten cases of unclassifiable proliferative glomerulonephritis manifesting glomerular monoclonal immunoglobulin G (IgG) deposits were identified retrospectively from the archives of the Renal Pathology Laboratory of Columbia University over the past 3 years (biopsy incidence 0.21%). RESULTS: The monoclonal immunoglobulins formed granular electron dense deposits in mesangial, subendothelial, and subepithelial sites, mimicking ordinary immune complex-mediated glomerulonephritis and producing a diffuse endocapillary proliferative or membranoproliferative glomerulonephritis. However, by immunofluorescence, the deposits were monoclonal, staining for a single light chain isotype and a single gamma subclass (including two IgG1kappa, one IgG1lambda, one IgG2lambda, four IgG3kappa, and one IgG3lambda). All cases stained for the three constant domains of the gamma heavy chain (CH1, CH2, and CH3), suggesting deposition of a nondeleted immunoglobulin molecule. Tissue fixation of complement was observed in 90% of cases, and 40% of patients had hypocomplementemia. Clinical presentations included renal insufficiency in 80% (mean serum creatinine 2.8 mg/dL, range 0.9 to 8.0), proteinuria in 100% (mean urine protein 5.8 g/day; range 1.9 to 13.0), nephrotic syndrome in 44%, and microhematuria in 60%. A monoclonal serum protein with the same heavy and light chain isotype as that of the glomerular deposits was identified in 50% of cases (including three IgGkappa and two IgGlambda); however, no patient had clinical or laboratory features of type 1 cryoglobulinemia. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 12 months). CONCLUSION: Glomerular deposition of monoclonal IgG can produce a proliferative glomerulonephritis that mimics immune-complex glomerulonephritis by light and electron microscopy. Proper recognition of this entity requires confirmation of monoclonality by staining for the gamma heavy chain subclasses.     

Immunotactoid glomerulopathy with microtubular deposits, with reference to the characteristics of Japanese cases

We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed microtubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for kappa light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITG occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia.     

Ultrastructural 'fingerprint' in cryoprecipitates and glomerular deposits: a clinicopathologic analysis of fingerprint deposits.

Organized glomerular electron-dense deposits with a fingerprint pattern are well known in some patients of lupus nephritis or cryoglobulinemia. In general, these two diseases are always discussed separately as the causes of such deposits. However, 3 of our 5 lupus patients with glomerular fingerprint deposits also had cryoglobulinemia. One of the remaining 2 patients died and the other was lost to follow-up. The purpose of our study was to seek an appropriate clinicopathologic assessment of fingerprint deposits. All these patients showed overt proteinuria, active urinary sediment, a high degree of activity of lupus nephritis, and diffuse proliferative glomerulonephritis (WHO class IV). Their cryoprecipitates and renal biopsy specimens were investigated by means of immunochemistry, immunofluorescence and electron microscopy. The ultrastructural 'fingerprint' structures were exactly the same in the cryoprecipitates and in the glomerular deposits in 2 of 3 lupus patients with cryoglobulinemia, as were IgG, IgM and IgA. Therefore, these observations furnish emerging morphologic evidence for the glomerular deposition of immune complexes of circulating cryoglobulins in lupus nephritis. In addition, electron microscopic fingerprint deposits on renal biopsy or cryoprecipitate can be regarded as a very sensible marker of concomitant or subsequent development of diffuse lupus nephritis. If the patient is accompanied by nephritic syndrome, an early trial of immunosuppressive therapy may be warranted.     

Acute renal failure in essential mixed cryoglobulinemia: precipitation and reversal by plasma exchange

A patient with essential mixed cryoglobulinemia was treated for deteriorating renal function with plasma exchange alone. This therapy was immediately followed by acute oliguric renal failure due to precipitation of the cryoglobulin within glomerular capillary loops, probably as a result of infusion of cold plasma. The composition of the intracapillary deposits reflected not only the variety of cryoglobulin but the rapidity of deposition. Renal function returned when plasma exchange was re-introduced, this time coupled with immunosuppressive chemotherapy. After resolution of the intraluminal caogula a membranoproliferative picture remained. Replacement fluids for plasma exchange in cryoglobulinemia should be warmed before infusion.     

Clinicopathologic features of glomerular lesions associated with hepatitis C virus infection in Japan

Background We determined the incidence of hepatitis C virus (HCV)-related glomerulonephritis in Japan and the glomerular localization of HCV-related antigens in this disorder. Methods We analyzed urinalysis findings in 100 consecutive Japanese patients with HCV chronic liver disease from 1993 to 1994. Immunohistochemical analysis using monoclonal or polyclonal antibodies to HCV-core antigen and polyclonal antibodies to HCV-envelope antigen was done on kidney specimens from 11 of 29 patients with antibody to HCV (anti-HCV-Ab). Results Eight of 100 patients had proteinuria, but only 2 cases (2%) were related to HCV nephropathy. Pathohistologic analysis showed 10 patients to have hepatic glomerulosclerosis, and 9 patients had mesangial proliferative glomerulonephritis involving primary immunoglobulin A nephropathy. Membranoproliferative glomerulonephritis was seen in 4 biopsy specimens that showed subendothelial electron-dense deposits and annular structures with characteristic cryogloblin. HCV core antigen was detected along the capillary walls with the same pattern as that of immunoglobulin G deposition and electron-dense deposits in 5 of 6 specimens from patients with both anti-HCV-Ab and HCV ribonucleic acid positive in the sera, but could not be detected in any of 3 specimens, from patients with anti-HCV-Ab but no HCV ribonucleic acid. Envelope antigen was not detected in the glomeruli of any specimens. Conclusions Glomerular lesions associated with HCV infection were characterized by deposition of immune complexes containing HCV core antigen and immunoglobulin G, and by the subendothelial deposition of cryoglobulin. These HCV-related glomerular diseases are rare in Japan (2% incidence), and these lesions should be distinguished from hepatic glomerulosclerosis related to advanced liver disease and other primary glomerular diseases.     

Glomerulonephritis, B monoclonal small lymphocytic lymphoma and mixed cryoglobulinemia

A novel association in the same patient with small lymphocytic lymphoma, type II cryoglobulinemia and glomerulonephritis is reported. This case is also characterized by a quite unusual sequence of glomerular alterations. A first renal biopsy showed severe endocapillary proliferative glomerulonephritis due to monocytic infiltration without any evidence of deposition of immune reactants. The immune deposits associated with type II cryoglobulinemia were only observed at a second renal biopsy performed five months later. This case shows that mononuclear cells can be responsible in and of themselves for severe glomerular damage, without deposition of immune material, and suggests that monocytic infiltration might be the first stage of type II cryoglobulinemia associated glomerulonephritis.     

Cryoglobulinemia and renal disease

PURPOSE OF REVIEW: Cryoglobulinemia occurs in a variety of clinical settings including lymphoproliferative disorders, infection and autoimmune disease. The worldwide pandemic of hepatitis C virus infection has resulted in a significant increase in its extrahepatic complications including cryoglobulinemia and renal disease. Here we review the types of cryoglobulins, mechanisms of cryoglobulin formation, links between hepatitis C virus and renal disease, and current approaches to therapy. RECENT FINDINGS: The prevalence of cryoglobulinemia in hepatitis C virus-infected individuals is surprisingly large and may be found in more than 50% of some infected subpopulations. Most of these patients will not have overt renal disease, but there is a population of unknown size of patients with subclinical glomerular disease that has the potential to become clinically significant. In cases of hepatitis C virus-associated cryoglobulinemia, treatment remains focused on eradication of viremia, but interventions directed at B lymphocytes are increasingly utilized. The mechanisms of cryoglobulin formation and renal injury remain largely obscure, but recent evidence implicates the innate immune system in the initiation of disease. SUMMARY: The most common renal injury associated with hepatitis C virus infection, in patients both with and without evidence of cryoglobulinemia, is membranoproliferative glomerulonephritis. There has been increasing focus on defining the mechanisms that link these processes and the evolution of renal injury in all clinical settings of cryoglobulinemia.     

Morphologic variants of light-chain deposition disease in the kidney

A variety of histologic changes have been observed in the kidneys of patients with light-chain deposition disease. We report 3 cases with kappa light chain deposition who presented with diverse clinical, histological, and ultrastructural features. All the cases were diagnosed by the presence of monoclonal kappa light chain deposits by immunohistochemical methods. Based on the present study and review of literature, four basic patterns of glomerular lesions are identified: (1) minimal glomerular changes without glomerular deposits, but with extensive tubular involvement; (2) mild glomerular changes with glomerular deposits; (3) focal or diffuse proliferative glomerulonephritis with or without crescents, and (4) nodular glomerulosclerosis resembling diabetic glomerulosclerosis. This pathological and clinical variability can cause diagnostic problems at initial presentation. A high index of suspicion is necessary along with appropriate laboratory data and routine staining for light chains.     

Association of overt glomerulonephritis and liver disease: a study of 34 patients.

Thirty-four patients with overt glomerulonephritis and chronic liver disease were studied. Kidney specimens were examined by light, electron and immunofluorescence microscopy. Plasma C3 levels were measured and a search for cryoglobulinemia was carried out in all patients. Twenty-six out of the thirty-four patients had an immune complex type glomerulonephritis (membrano-proliferative glomerulonephritis or glomerulosclerosis with mesangial deposits) suggestive of hepatic glomerulonephritis. The glomerular deposits almost always contained IgA and very frequently other immunoglobulins as well as C3. The membrano-proliferative glomerulonephritis was characterized by severe renal symptoms, mixed cryoglobulinemia and the frequent finding of low C3 levels. These data suggest that there is a linkage between liver disease and glomerulonephritis. The immunomorphological type of glomerulonephritis and the cryoglobulinemia are both suggestive of an immune complex disease. The lowering of the C3 levels could be due to activation of complement components by immune complexes, to hepatic hyposynthesis, or to a combination of the two.