乙型肝炎病毒DNA与IgA肾病发病的关系

目的：探讨乙型肝炎病毒(HBV)感染与IgA肾病发病的关系。方法：50例血清HBV标志或肾组织HBV抗原阳性的IgA。肾病患者作为研究对象，应用原位分子杂交技术和Souther blot技术检测肾组织中HBV DNA。结果：50例IgA肾病患者中，血清HBsAg阳性17例(34％)；肾组织HBAg阳性48例(96％)，HBAg在肾小球中阳性率为82％(41／50)，其中HBsAg为58％(29／50)，HBcAg为42％(21／50)；除了肾小球，47例(94％)患者BsAg和HBcAg。肾小管上皮细胞亦有阳性沉积，分别为28例(56％)和39例(78％)；原位分子杂交证实50例患者肾组织HBV DNA阳性率为92％(46／50)，其中肾小管上皮细胞、肾小球细胞HBV DNA阳性率分别为72％(36／50)和82％(41／50)。Southem blot技术证实在50例患者肾组织中34例有整合型HBV DNA，阳性率为68％。结论：HBV感染与IgA肾病的发病密切相关，HBV可能直接感染肾组织并原位表达HBV DNA而参与了IgA肾病的发病。     

乙肝病毒血症与原发性肾炎患者肾组织内乙肝抗原沉积的相关性研究

目的：探讨乙型肝炎病毒（HBV）感染与原发性肾小球肾炎（肾炎）发病的联系。方法：用间接免疫荧光法检测230例原发性肾炎 患肾活检冰冻切片组织内HBsAg和HBcAg的沉积情况。按血清HBV感染标志物检测情况分血清阳性和阴性两组进行分析,以及按发病年龄和病理类型进行分析。结果：在230例原发性肾炎中,肾组织内HBsAg和HBcAg的阳性率分别为18．7％和16．8％,乙肝肝炎抗原（HBAg)总阳性率为20％。血清HBV感染标志物阳性率为39．6％。血清阳性组的肾组织内HBAg阳性率明显高于血清阴性组,有统计学意义。分析显示,这种相关性在小儿组和成人组中同样存在,相关的病理类型见于膜性肾病。结论：血清HBV感染与原发性肾炎（包括成人原发性肾炎 ,特别是原发性膜性肾病）的发病有密切联系。     

乙型肝炎病毒相关性肾炎患者临床与病理的关系

目的探讨乙型肝炎病毒相关性肾炎（HBV-GN）患者临床与病理的关系。方法回顾性分析经肾活检确诊的52例HBV—GN患者的肝功能、肾功能、血脂、24h尿蛋白定量、乙型肝炎病毒标志物HBV-DNA等,应用乙肝免疫组织化学方法检测40例血清乙型肝炎病毒（HBV）阳性和12例HBV阴性患者肾组织中乙型肝炎病毒表面抗原（HBsAg）、乙型肝炎病毒核心抗原（HBcAg）和乙型肝炎病毒e抗原（HBeAg）,对比两组患者的临床表现和肾组织病变特征。结果HBV阳性的临床表现以肾病综合征最多见（38例,72％）,病理类型以膜增殖性肾炎（16例,40％）和重度系膜增生性肾炎12例（30％）多见。两组之间的临床表现和肾组织病理类型无显著性差异（P〉0．05）。HBV抗原除在肾小球沉积外,肾小管常有阳性表达,尤其肝功能异常和HBV-DNA阳性者HBcAg肾小管阳性率达36％,高于肾小球的21％,有显著性差异（P〈0．05）。血清HBeAg阳性者肾小球HBeAg的检出率显著高于血清HBeAg阴性者（P〈0．05）。结论HBVGN的临床表现、病理类型与原发性肾小球疾病类似。HBV可能直接感染肾组织导致HBV-GN的发生。肾小球HBeAg与血清HBeAg阳性者呈正相关。     

68例伴有肾组织乙肝病毒抗原沉积的肾炎患者临床和病理分析

目的：探讨血清乙肝病毒（HBV）标志物与肾组织HBV抗原沉积、肾病理之间的关系，了解乙肝病毒相关性肾炎（HBV—GN）的临床和病理特点。方法：收集成人肾组织中检测到HBsAg和／或HBcAg沉积的肾炎患者68例（以下称沉积阳性组）。随机抽取同期肾穿合并有慢性乙型肝炎但肾组织中不伴HBsAg和／或HBcAg沉积的肾炎患者24例作为对照组（以下称沉积阴性组）。两组均采用间接免疫荧光法检测肾活检组织冰冻切片中HBsAg和HBcAg，荧光定量PCR法检测血清HBV—DNA水平。结果：（1）两组患者在血压、血尿和蛋白尿程度以及肾功能水平均无统计学差异；（2）沉积阳性组肾病理以IgA肾病（IgAN，占51．5％）和不典型膜性肾病（MN，占38．2％）为主；沉积阴性组则以系膜增生性肾炎（MsPGN，占50％）为主；（3）68例患者中13例血清HBV标志物阴性或仅有HBsAb阳性，血HBV—DNA病毒载量〈100拷贝／ml的患者肾组织中检测到HBsAg和俄HBcAg沉积，且免疫荧光显示免疫球蛋白和补体沉积均在3种以上，满堂亮者7例（53．8％）：光镜显示不典型MN9例（69．2％），IgAN3例，MPGN1例。结论：对于成年人依据临床难作出HBV—GN诊断。成人HBV—GN病理表现具有多样性，以IgAN和不典型MN为主，其次为MPGN和MsPGN，FSGS少见；肾组织HBV抗原沉积现象可以出现在血清HBV标志物阴性或仅HBsAb阳性的患者，提示应重视肾组织HBV抗原检测，尽可能降低HBV—GN的漏诊率，尤其是血清HBV标志物阴性的患者。     

43例狼疮肾炎患者肾组织内乙型肝炎病毒抗原及DNA的检测

狼疮肾炎（lupusnephritis,LN）的病因及发病机制尚不清楚,有文献报道LN肾穿刺组织HBAg的检出率为48％~63.8％[1,2]。我们对43例LN肾穿刺材料应用原位分子杂交、免疫组织化学染色及其观标记技术,部分病例辅以Southem印迹杂交,探讨LN肾组织HBAg及HBVDNA的阳性情况及其意义。一、材料和方法1．病例选择：43例LN肾穿刺组织标本选自1994~1996年间上海医科大学附属华山医院、中山医院、儿科医院和上海八五医院肾内科住院病例。选用同时期血清及肾组织HBV感染标志物附性的30例肾小球肾炎（系膜增生性肾炎25例,局灶节段性肾炎3例,…     

白细胞介素17在IgA肾病肾小管间质的表达及意义

目的观察白细胞介素17（IL-17）在IgA肾病患者肾组织的表达,探讨IL-17在IgA肾病中的临床及病理意义。方法选择51例IgA肾病患者肾组织活体检查采用Katafuchi半定量积分标准和免疫组织化学技术进行病理学积分和检测IL-17的表达,同时检测51例IgA肾病患者中30例外周血单个核细胞（PBMCs）中IL-17、转化生长因子β1（TGF-β1）、IL-6、IL-23、IL-βmRNA的表达。结果正常肾组织中未见IL-17表达。51例IgA肾病患者中,21例肾小管上皮细胞胞质IL-17表达阳性,2例肾间质淋巴细胞IL-17表达阳性,总阳性率为45．10％;并且随着肾小管间质病变加重,IL-17的表达逐步增多。IgA肾病患者PBMCs中IL-17、IL-6、IL-23、IL-1βmRNA的表达较正常人显著升高（P〈0．01）,TGF-β1mRNA的表达与正常人比较无统计学差异（P〉0．05）,IL-17mRNA与TGF-β1、IL-β1mRNA的表达呈正相关（r=0．67、0．71,P〈0．05）。IgA肾病患者肾小管间质IL-17的表达水平与尿位相畸形红细胞计数、肾小管间质病理积分呈正相关（r=0．60、0．67,P〈0．05）,IL-17mRNA的表达与血肌酐呈正相关（r=0．66,P〈0．05）。结论IgA肾病患者肾小管间质及外周血中IL-17表达增高,并与临床及病理预后指标密切相关,提示IL-17可能是参与IgA肾病发病及进展的因素之一。     

IgA肾病患者高血压的相关因素分析

目的探讨IgA肾病患者高血压的相关因素。方法经肾脏活体组织检查确诊的IgA肾病患者120例,采用单因素和多因素Logistic回归分析IgA肾病患者高血压发生的相关因素。结果120例IgA肾病患者中伴有高血压患者39例（占32．5％）。单因素分析发现,24h尿蛋白定量≥2．0g、尿素氮（BUN）≥8mmol／L、血肌酐（SCr）≥133μmol／L、肾小球率过滤（GFR）〈60ml·min^-1·（1．73m^2）^-1、高尿酸血症、贫血、肾小球慢性病变指数≥4分、肾间质炎症细胞侵润〉25％、肾小管萎缩和问质纤维化〉25％、肾小动脉管壁增厚、Lee分级Ⅳ～Ⅴ级与IgA肾病患者高血压相关。多因素Logistic回归结果显示,蛋白尿程度、GFR水平为IgA肾病高血压发生的独立危险因素。结论32．5％的IgA肾病患者伴有高血压,蛋白尿程度、GFR水平是高血压的独立危险因素。     

改良免疫组化法在诊断乙型肝炎病毒相关性肾炎的应用研究

目的：探讨改良免疫组化染色法在诊断乙型肝炎病毒相关性肾炎（HBV-GN）的应用前景。方法：改良免疫组化染色法采用高温高压＋XXIV型蛋白酶消化的抗原修复法,行一抗和二抗两步孵育法,其中二抗与酶标多聚体相连。病人肾组织标本同时行免疫荧光染色法检测作对照。结果：（1）40例血清学HBsAg阳性患者的肾穿组织标本中,改良免疫组化染色法HBsAg阳性27例,阳性率为67．5％;HBcAg阳性7例（其中HbsAg同时阳性6例,HbsAg阴性1例）,阳性率为17．5％;HbsAg、HBcAg同时阴性12例。免疫荧光染色法HBsAg阳性29例（72．5％）;HBcAg阳性10例（25．0％,均同时呈HbsAg阳性）;HbsAg、HBcAg同时阴性11例。（2）两种染色比较,HbsAg阳性率相近（改良组化67．5％VS荧光72．5％）,其中同时阳性的有22例,同时阴性的5例,总一致率为67．5％（27／40）,阳性一致率在改良免疫组化染色中为81．5％（22／27）,在免疫荧光染色中为75．9％（22／29）。（3）10例血清丙氨酸转氨酶升高的患者中,改良免疫组化HbsAg染色阳性9例,免疫荧光染色阳性7例;血白蛋白〈30g／L而尿Pro定量未达到〉3．5g／24h的患者7例;6例病理呈膜性或／和膜增殖性肾炎（其中改良组化染色阳性5例,荧光染色阳性3例）。有2例行肝组织穿刺活检,病理显示肝脏病变。结论：改良免疫组化染色可提高HBV-GN的乙肝抗原检测率,有临床应用推广价值。     

IgA肾病是否与乙型肝炎病毒有关？

探讨ＩｇＡ肾病与乙型肝炎病毒的关系。方法采用免疫组化技术检测ＩｇＡ肾病患者肾组织中ＨＢＶ抗原及Ｓｏｕｒｔｈｅｒｎ印迹分子杂交技术检测肾组织中ＨＢＶＤＮＡ。结果８５例ＩｇＡ肾病患者血清ＨＢｓＡｇ阳性１５例（１７．６５％），肾组织ＨＢＶ抗原阳性２６例（３０．５９％），其中肾小球阳性１８例（５７．１４％），ＨＢｃＡｇ在肾小管和肾间质中阳性分别为９例（３４．６７％）和２例（７．６９％）；２例测肾组织ＨＢＶＤＮＡ，１例阳性；肾组织ＨＢＶ抗原阳性组比阴性组临床和病理改变更严重。结论乙型肝炎病毒与ＩｇＡ肾病的发病密切相关     

IgA肾病患者尿足细胞排泄与临床病理相关性分析

目的观察原发性IgA肾病患者尿足细胞排泄、肾小球足细胞病变,分析其与临床病理之间的关系。方法50例经肾活检明确诊断的IgA肾病患者和10名健康志愿者,利用podocalyxin（PCX）作为标记蛋白,标记尿液和肾组织足细胞,收集患者肾活检时临床资料,各项病理指标和肾组织足细胞PCX荧光表达采用不同的半定量积分法进行评分,电镜检测肾小球外周袢的足突宽度。结果①IgA肾病患者中尿足细胞染色阳性为32例（64％）,较健康对照者有统计学差异。②IgA肾病伴尿足细胞阳性患者尿蛋白水平、血肌酐（SCr）、平均动脉压（MAP）较尿足细胞阴性患者增高,血浆白蛋白（Alb）、肾小球滤过率（GFR）降低（P〈0．05）。③光镜示IgA肾病伴尿足细胞阳性患者肾小球硬化程度、新月体发生率较尿足细胞阴性患者明显增高（P〈0．05）,但小管间质病变与肾组织足细胞PCX表达阳性指数,2组比较无统计学差异。④电镜结果提示IgA肾病患者尿足细胞阳性足突宽度明显增宽（P〈0．05）。结论足细胞尿是反映肾脏疾病轻重的一个指标,足细胞尿与肾脏病理类型有一定关系,IgA肾病患者尿足细胞排泄指标是否能够独立预测患者的预后还有待证实。     

The existence and significance of hepatitis B virus DNA in glomerulonephritis

Summary: In order to investigate the role of hepatitis B virus (HBV) in the pathogenesis of glomerulonephritis 50 cases of glomerulonephritis with HBV antigenaemia and/or hepatitis B antigen (HBAg) detected by immunohistochemistry in renal tissue were collected. the distribution and localization of HBV DNA were observed by using in situ hybridization. In addition, Southern blot analysis was performed on 23 of the 50 cases in order to reveal the state of renal HBV DNA. Thirty-six cases (72%) were found to be HBV DNA positive by in situ hybridization, which localized in the nucleus of tubular cells. In 26 cases HBV DNA was detectable in the nucleus of glomerular mesangial and epithelial cells as well as the mesangial matrix. Seventeen of the 23 cases were proved to be HBV DNA positive in Southern blot analysis (82%). Three of these cases were identified with non-replicating free HBV DNA, while 14 cases were the integrated form. the results of this study showed that the renal tissue was infected with HBV; however, it was considered that it may be possible that the HBAg deposited on glomeruli was not only from circulation but also from the HBV infected glomerular cells although the evidence of this is not conclusive. In addition to the humoral immune injury mediated by HBAg-hepatitis B antibody (HBAb) immune complexes the cellular immune injury mediated by target antigen (hepatitis B core antigen; HBcAg) might be also involved in the pathogenesis of HBV glomerulonephritis (GN) associated GN.     

乙型肝炎病毒感染与肾小球肾炎

目的研究乙型肝炎病毒（ＨＢＶ）感染与肾小球肾炎，尤其是与ＩｇＡ肾病（ＩｇＡＮ）、狼疮肾炎（ＬＮ）间的关系，并初步观察α干扰素（αＩＦＮ）对成人乙肝相关性肾炎（ＨＢＶＧＮ）的疗效。方法对１５７例肾活检标本采用免疫组织化学的方法检测肾组织中ＨＢＡｇ，配对比较３２例ＩｇＡＮ，３０例ＬＮ中ＨＢＡｇ阳性组与阴性组肾组织病理改变，和４２例ＧＮ中ＨＢｃＡｇ阳性组与阴性组对激素治疗的反应，并随访３例ＨＢＶＧＮ经αＩＦＮ治疗的临床演变。结果ＩｇＡＮ中ＨＢｃＡｇ阳性组肾小管及间质病变程度均较阴性组严重（Ｐ＜００５）；ＬＮ中ＨＢｃＡｇ阳性组肾小球硬化及间质炎症程度较阴性组显著（Ｐ＜００５）；ＨＢｃＡｇ阳性组对激素治疗的反应较阴性组差（Ｐ＜００５）；３例ＨＢＶＧＮ经αＩＦＮ治疗后临床症状缓解。结论肾小球肾炎部分病例起病与ＨＢＶ感染有关，ＩｇＡＮ、ＬＮ与ＨＢＶ感染有相关性，αＩＦＮ对成人ＨＢＶＧＮ可能有良好的治疗作用。     

The association of WISP-1 expression in IgA nephropathy patients with renal interstitial fibrosis

Objective To investigate the relationship between the expression of Wnt induced secreted protein-1 (WISP-1) and the fibrosis of renal biopsy tissue in IgA nephropathy (IgAN) patients. Methods Fifty-three patients firstly diagnosed as IgA nephropathy by renal biopsy were included and classified according to Oxford and Lee's classification. Sixteen patients with MCD entered the fibrosis negative control group, and fourteen healthy adults entered the normal control group. The expression of WISP-1 in renal tissues and serum of all subjects were detected by immunohistochemistry and ELISA respectively. Results Immunohistochemistry results showed that WISP-1 was not expressed in MCD patients and normal human kidney tissues, which was abundantly deposited in renal tissue of patients with focal proliferative IgAN with renal interstitial fibrosis. The serum level of WISP-1 in IgAN patients was significantly higher than that in normal subjects (P=0.015) and MCD patients (P=0.030). In the subgroup analysis of IgAN renal fibrosis, the serum concentration of WISP-1 of fibrosis grade between 0-10% (F1 group) and fibrosis＞25% (F3 group) were significantly higher than that in the normal group and the MCD group (all P＜0.05). There was no significant difference between F2 group (10%＜fibrosis≤25%) and normal group or MCD group (P＞0.05). Conclusions The expression of WISP-1 in serum and renal tissue of renal interstitial fibrosis IgAN patients is higher than that of normal and MCD patients without renal fibrosis, and the IgAN patients' serum level of WISP-1 is significantly increased in fibrosis lower score group. The expressions of WISP-1 in serum and renal tissue are related to the occurrence of IgAN renal interstitial fibrosis, in which WISP-1 may play an important role as an early precursor factor in the pathogenesis of IgAN renal interstitial fibrosis.     

Clinical Characteristics and Treatment of Patients with IgA Nephropathy and Hepatitis B Surface Antigen

Background: The aim of this study is to investigate the clinical characteristics and our experience of treating patients with IgA nephropathy (IgAN) and IgA nephropathy with hepatitis B surface antigen (HBs-IgAN). Methods: From 1996 to 2011, biopsy-proven IgAN was diagnosed in 477 patients and 22 (4.6%) had hepatitis B surface antigen (HBsAg). Of these, we included 360 patients who had more than 6-month follow-up period, and compared clinical characteristics and renal function decline between the patients with IgAN and HBs-IgAN. Results: Of 360 patients, 22 were classified as HBs-IgAN. There were no differences in the clinical characteristics and renal function decline between idiopathic IgAN and HBs-IgAN (–0.01 vs. –0.17 mL/min per 1.73 m²/month, p = 0.319). Of 22 patients with HBs-IgAN, nine had hepatitis B virus (HBV) replication marker (RM), of which six were treated with anti-viral agents. However, there were no differences in renal function decline and urinary protein excretion between patients who did or did not receive anti-viral therapy. Five patients with HBs-IgAN received corticosteroid therapy. Of these, three without HBV RM and one with HBV RM who received entecavir did not exhibit active viral replication, whereas the other patients with HBV RM experienced viral replication after lamivudine was discontinued. Conclusion: There were no differences in the clinical characteristics and prognosis between the patients with IgAN and HBs-IgAN. Further, there were no differences in renal function decline and urinary protein excretion between patients with and without anti-viral therapy. Anti-viral therapy may be considered for treating patients with HBs-IgAN receiving immunosuppressants according to HBV RM.     

Human cytomegalovirus in immunoglobulin A nephropathy: detection by polymerase chain reaction.

Human cytomegalovirus (HCMV) has been suspected to participate in the pathogenesis of IgA nephropathy (IgAN). However, with regard to the presence of HCMV in the renal tissue of IgAN, conflicting results have been reported using a variety of different techniques. Renal biopsies of 29 patients with IgAN, of 7 with focal segmental glomerulosclerosis (FSGS) and of 11 normal kidneys were analyzed for the presence of HCMV-DNA using the polymerase chain reaction. HCMV-DNA was detected by hybridization with digoxigenin-labelled probes in 14 of 19 analyzed frozen renal biopsies from patients with IgAN. However, only 1 of 17 renal biopsies of IgAN embedded in paraffin was positive for HCMV-DNA. Furthermore, HCMV-DNA was detected in 4 of 18 frozen normal kidneys but in none of the tissues from patients with FSGS. The present results provide further evidence of an association between the presence of HCMV in renal tissue and IgAN.     

Hepatitis-B virus associated nephropathies: a clinicopathological study in 14 children

Hepatitis B virus (HBV)-associated glomerulonephritides have been increasingly reported, and the association between HBV and glomerulopathy is striking, especially in children. In this study, we investigated clinical and immunohistological features of HBV-associated glomerulonephritis in 14 children aged from 2.5 to 16 years (mean 10 years). The nephrotic syndrome was present in 9 (64%) and the nephritic syndrome in 8 children (57%). Five children had both nephrotic and nephritic syndrome together (35%). Renal insufficiency was determined in 4 of 14 patients (28%). Surface antigen (HBsAg) was present in all, with no history of clinically apparent hepatitis. Investigation of all renal tissue samples with light and immunofluorescence microscopy confirmed the diagnosis of membranous glomerulonephritis (MGN) in 6, membranoproliferative glomerulonephritis (MPGN) in 7, and IgA nephropathy (IgAN) in 1 child. Renal tissue samples were studied by the immunoperoxidase method for HBsAg in all cases; only in 4 children was HBsAg detected in the glomeruli. Examination of liver tissue samples was available in 4 cases, revealing chronic hepatitis in all, with additional development of cirrhosis in 1 and the presence of HBsAg in hepatocytes in all. Of the patients, 8 received corticosteroid treatment; 1 of them achieved a complete remission, while 4 had a partial remission with persistent proteinuria and hematuria. Four patients who received no treatment had a spontaneous remission within 5 months to 10 years following the onset of the renal disease. Two patients died of renal failure, while 1 died of intercurrent sepsis. The patient with IgAN received interferon-alpha 2a and lamuvidine, which resulted in a remission and a marked decrease in HBV DNA titer. The remaining 2 were lost to follow-up. Although MGN has been reported as the nephropathy most commonly associated with HBsAg antigenemia in adults, our study revealed that MPGN could occur in children as well as MGN, without any clinical or historical evidence of hepatitis. The present study provides further evidence for a causal relationship between HBV hepatitis and HBs antigenemia-related glomerulonephritides in the pediatric age group. It also indicates the prognosis (71%) of the associated nephropathies with or without treatment is quite favorable in childhood.