儿童Alport综合征临床与病理分析

目的：了解Alport综合征患儿的临床与病理特点。方法：回顾性分析我院2007年2月至2009年2月10例诊断为Alport综合征患儿的临床及病理资料。结果：男7例,女3例,年龄2岁至6岁7月,平均3岁2月。10例患儿中5例有明确家族史;X连锁显性遗传8例,常染色体隐性遗传2例。临床表现为孤立性血尿5例,血尿合并蛋白尿3例,大量蛋白尿1例,肾病综合征1例;肾组织病理示：8例光镜为系膜增生性肾小球肾炎,2例为局灶节段性肾小球硬化;免疫荧光均以IgM沉积为主;电镜下1例出现典型的肾小球基底膜病变。所有患儿肾脏IV型胶原α链分布异常。结论：Alport综合征临床表现多样。肾组织病理光镜下主要以系膜增生为主,免疫荧光以IgM沉积为主。电镜下基底膜病变不明显,需结合IV型胶原α链免疫荧光检测明确诊断。［中国当代儿科杂志,2010,12（3）：188-191］     

江西地区肾脏病儿童757例肾活检的病理与临床资料分析

目的 探讨儿童肾脏疾病的病理特点及其与临床表现的关系.方法 回顾性分析2002年2月-2010年6月在江西省儿童医院行肾活检的757例肾病患儿的病理及临床资料.将肾活检组织分别行光镜、免疫荧光、免疫组织化学及电镜检查.肾活检组织均作苏木精-伊红(HE)、过碘酸雪夫反应(PAS)、六胺银(PASM)及Masson染色;免疫荧光检测IgG、IgA、IgM、C3、C4、C1q.有乙型肝炎病毒感染证据者肾组织同时行乙型肝炎表面抗原(HBsAg)、乙型肝炎e抗原(HBeAg)、乙型肝炎核心抗原(HBcAg)免疫组织化学.参照中华医学会肾脏病分会2000年制定的标准进行病理分型,结合临床和病理资料进行统计分析.结果 1.肾活检病例757例中原发性肾小球疾病537例(70.97%),其中肾病综合征265例(49.35%),孤立性血尿99例(18.44%);继发性肾小球疾病211例(27.84%),其中紫癜性肾炎144例(68.25%),乙肝相关性肾炎47例(22.27%);遗传性肾小球疾病9例(1.19%).2.原发性肾小球疾病病理类型最多的是系膜增生性肾小球肾炎277例(51.58%);继发性肾小球疾病中紫癜性肾炎最多,为144例(68.25%),其病理分级以Ⅱb～Ⅲb为主,占79.17%;遗传性肾小球疾病中Alport综合征8例;薄基底膜肾病1例.结论 江西地区儿童肾脏疾病以原发性肾小球疾病为主,病理改变以系膜增生性肾小球肾炎占绝大多数;继发性肾小球疾病中除以紫癜性肾炎为主外,乙肝相关性肾炎并不少见.     

儿童C3肾小球肾炎6例临床与病理分析

目的分析6例儿童C3肾小球肾炎的临床表现、病理特征及治疗反应,旨在提高儿科医生对此病的认识和处理。方法对2010年9月至2016年6月在吉林大学第一医院小儿肾病科确诊为C3肾小球肾炎且有完整临床资料的6例患儿的临床表现、病理改变、疗效及预后进行回顾性分析。结果(1)临床表现及实验室检查:以血尿为首发症状2例,以血尿和蛋白尿为首发症状4例;其中表现为肾炎综合征3例,肾病综合征1例;6例患儿补体C3均降低;补体C4均正常;(2)病理特点:6例患儿免疫荧光均可见补体C3强阳性沉积;光镜下表现为系膜增生性肾小球肾炎5例,表现为毛细血管内增生性肾小球肾炎1例;电镜下3例可见电子致密物沉积,3例未见电子致密物沉积;(3)治疗及预后;均予肾炎常规治疗,2例有新月体形成者加用糖皮质激素治疗。随访6~42个月,预后较好。结论本组C3肾小球肾炎患儿以血尿和(或)蛋白尿为主要表现,免疫荧光见C3强阳性沉积,光镜表现多以系膜增生性肾小球肾炎为主,电镜可表现为电子致密物沉积,短期预后较好。     

儿童IgA 肾病合并Alport 综合征2 例报告并文献复习

目的探讨IgA肾病的诊断和鉴别诊断的思路。方法回顾分析2例IgA肾病患儿的临床资料,并复习相关文献。结果2例患儿均为男性,年龄分别为6岁、7岁,临床表现为大量蛋白尿(以白蛋白为主)、低白蛋白血症、高胆固醇血症及持续镜下血尿,均符合肾病综合征诊断,但激素及免疫抑制剂治疗效果欠佳。肾脏病理免疫荧光结合光镜检查符合轻、中度系膜增生性IgA肾病(M1E0S0T0);电镜提示肾小球基底膜病变(分层、断裂、薄厚不均),Alport综合征不除外。进一步基因检测证实存在COL4A5致病基因突变。结论 IgA肾病和Alport综合征二者合并发生较为罕见,对于治疗效果欠佳特别是有相关家族史的IgA肾病患儿,应注意二者同时发生的可能。     

儿童孤立性血尿23例临床病理分析

目的探讨小儿孤立性血尿的病理类型。方法对符合孤立性血尿诊断标准的23例患儿,行B超定位引导,局麻或全麻后,采用负压吸引行小儿经皮肾活检;肾穿标本用特制邮寄盒远程送检,肾组织进行光镜、电镜及免疫组织化学检查。结果膜性增生性肾小球肾炎(MsPGN)8例(34.9%),微小病变性肾病(MCN)5例(21.7%),IgA肾病(IgAN)4例(17.4%),薄基底膜肾病(TMN)3例(13%),Alport′s综合征(AS)、局灶性节段性硬化(FSGS)I、gM肾病(IgMN)各1例(各4.3%)。结论孤立性血尿患儿以MsPGN、MGA及IgAN为主,TMN、FSGS占一定比例,极少数患儿可出现严重肾小球硬化改变。     

血尿306例临床与病理分析

目的 研究血尿患儿的临床特征及肾脏病理特点。方法 对以血尿为首发及主要表现并具备肾活检病理诊断的306例血尿患儿的临床与病理资料进行回顾性分析。结果 IgA肾病占42％，系膜增殖性肾小球肾炎占38％，薄基底膜肾病占6％，Alport综合征占3％，其他占11％。结论 血尿严重程度与病理类型无明显关系，伴大量蛋白尿或高血压者病理损害相对较严重。     

伴有新月体形成的原发性IgA肾病的临床与病理分析

目的了解儿童伴有新月体形成的原发性IgA肾病的临床与病理特点.方法对29例伴新月体形成的原发性IgA肾病患儿的临床及病理资料进行分析,并依受新月体累及的肾小球比例分组比较,≥50%(A组),9例;<50%(B组),20例.结果 (1)临床方面29例均有血尿+蛋白尿,尿蛋白≥1 g/24 h 者22例(76%)和肉眼血尿86%,水肿、高血压、肾功能异常者均不及半数.A组以肾病综合征和急进性肾炎为主,持续性肉眼血尿、大量蛋白尿、高血压、肾功能衰竭均较B组明显(P<0.05).B组无症状性血尿+蛋白尿者65% .(2)病理方面新月体形成累及肾小球5%～85%, A组为52%～85%(其中新月体型IgA 肾病10%),B组5%～40%,以细胞性为主.均有系膜增生和小管-间质病变,球囊粘连易见. 两组比较A组系膜增生严重、小球硬化和小管灶状萎缩明显(P<0.05),B组球囊粘连多见(P<0.05).(3)免疫荧光均有IgA+IgM+C3沉积,合并IgG沉积者18例(62%),其中5例(17%)为"满堂亮"(A组占4例).未见一例单纯IgA沉积.结论伴有新月体形成的原发性IgA肾病临床均有血尿合并蛋白尿,以持续性肉眼血尿和大量蛋白尿为主;以弥漫性系膜增生为主要病理改变,易见球囊粘连和小管-间质病变;沉积物以IgA+IgM型或IgA+IgM+IgG型多见,部分呈"满堂亮";较一般型IgA肾病临床、病理明显加重.     

早期诊断Alport′s综合征5例及文献复习

目的探讨早期诊断Alport′s综合征(AS)的方法及文献复习。方法临床表现为孤立性血尿和肾病综合征(NS)5例,均行肾组织光镜、免疫荧光电镜检查和皮肤基底膜(EBM)Ⅳ型胶原α链免疫测定,2例行肾小球基底膜(GBM)Ⅳ型胶原α链免疫测定。结果患儿光镜均表现肾小球轻微病变或局灶节段增生,电镜表现肾小球基底膜弥漫性变薄,无诊断意义。患儿EBM和GBMα1均( )连续,但3例男童EBMα5链(-)、GBMα3、α5(-);2例女童EBMα5( )但不连续,GBMα3、α5( )但不连续,达到早期诊断目的。结论对于孤立性血尿、NS(激素治疗耐药),肾活检电镜表现基底膜变薄患儿,有条件应常规进行皮肤和GBMⅣ型胶原α链检测,为诊断和鉴别诊断提供依据。     

泌尿生殖系统疾病

051110儿童单纯性血尿105例病理分析/张桂菊…∥北京医学.-2004,26(4).-254～256对105例符合单纯性血尿诊断标准的患儿行肾活检术,肾组织进行光镜、电镜及免疫荧光检查。结果:薄基底膜肾病36例(34.3%),IgA肾病35例(33.3%),系膜增生性肾小球肾炎17例(16.2%),轻微病变7例(6.7%),Alport综合征6例(5.7%),局灶节段性硬化2例(1.9%),IgM肾病2例(1.9%)。表1参13(原文摘要)051111儿童淋菌性尿道炎36例临床分析/吴伟庆∥中国皮肤性病学杂志.-2004,18(10).-616结果:36例中男女比例为1∶5;8/21例检出CT或/和UU感染;经用青霉素、壮观霉素、头孢三嗪等…     

单纯性血尿患儿肾组织免疫病理及肾小管CD_(40)的表达

目的观察单纯性血尿患儿肾组织免疫病理变化及肾小管CD40的表达,探讨免疫炎症反应在其发病机制中的作用。方法选取2004年1月-2007年3月在苏州大学附属儿童医院就诊并行肾活检的单纯性血尿患儿32例。全部患儿肾活检后,取部分肾组织经快速冷冻切片,进行常规病理和免疫荧光分析。同时采用免疫组织化学方法检测其肾小管CD40表达情况,采用计算机图像分析系统拍摄数字图像。采用Image-Pro Plus 5.02病理图文分析系统,计算各处理组肾小管CD40阳性表达率,并进行统计学分析。结果不同临床类型的单纯性血尿患儿肾组织病理主要表现为系膜增生性改变,其中轻度增生和弥漫性增生分别占全部患儿的37.50%和46.88%,伴局灶/阶段性细胞增生、坏死、纤维化和肾小球硬化者5例(占15.63%),未见膜性肾病和弥漫性硬化性肾小球肾炎病例。不同临床类型、病理类型的患儿均见IgA和(或)IgM沉积,其中系膜区以IgA沉积为主者占全部患儿的62.50%,且常伴IgM和(或)IgG沉积,单纯表现为IgA沉积者仅1例。以IgM沉积为主(不伴IgA)者占全部患儿的37.50%,其中仅有IgM者9例,占全部患儿的28.13%,伴IgG沉积...     

91例儿童Alport综合征临床、病理特点及误诊分析

目的探讨儿童Alport综合征(AS)临床、病理特点和诊治情况,以提高对AS的认识。方法收集确诊的91例AS患儿临床资料进行回顾性分析。结果 91例患儿均有血尿,86例伴有蛋白尿。61例X连锁显性遗传AS(XL-AS)患儿有阳性家族史。肾活检的82例患儿中74例有轻度或轻-中度系膜增生,48例系膜区少量免疫复合物,53例肾小球基底膜(GBM)有变薄、增厚和撕裂。63例进行了肾组织Ⅳ型胶原α3、α5链免疫荧光检测,确诊AS 58例,其中53例符合XL-AS,5例符合常染色体隐性遗传AS。91例AS患儿中,58例通过肾组织Ⅳ型胶原α3、α5链免疫荧光确诊,21例通过电镜确诊,1例通过皮肤活检确诊;12例基因诊断确诊。发现6个COL4A5基因新突变。45例曾被误诊其他疾病,其中41例接受过激素和/或免疫抑制剂治疗。结论儿童AS临床表现缺乏特异性,特征性GBM电镜改变仅见于部分患儿,本区域儿童AS误诊误治率仍较高。COL4A5基因新突变比例较高。     

单中心儿童肾活检1 579例临床和病理类型分析

目的 了解肾穿刺患儿病理特点及其与临床表现的关系,以及疾病谱变迁。方法 调取华中科技大学同济医学院附属同济医院儿科1989至2012年行肾活检病例的临床分类和病理学分型资料,依据年龄（<1、～3、～6、～12和～18岁）和性别分组进行构成比的比较和分析,以2001年为时间节点分为2个阶段分析疾病谱的变化趋势。结果 1 579例肾活检患儿进入分析,平均肾穿刺年龄（9.3±3.2）岁,男女比例1.92∶1。①肾活检患儿中原发性肾小球疾病949例（601%）,继发性肾小球疾病493例（31.2%）,遗传性肾脏疾病130例（8.2%）;原发性肾小球疾病中肾病综合征、单纯血尿、急性肾炎分别占44.8%、26.2%和15.3%;继发性肾小球肾炎中紫癜性肾小球肾炎、HBV相关性肾炎（HBVGN）和狼疮性肾炎（LN）分别占55.4%、22.9%和18.4%;遗传性肾脏疾病中薄基底膜病和Alport综合征分别占50.0%和462%。②949例原发性肾小球疾病的病理类型以轻微病变/微小病变(24.8%)、IgA肾病(21.0%)和系膜增生性肾小球肾炎(191%)为主;女性新月体性肾小球肾炎构成比显著高于男性。③肾病综合征构成比随年龄增长呈逐渐减少趋势,单纯血尿构成比在～12岁组最高（31.0%）,急性肾炎和慢性肾炎构成比随年龄增长呈逐渐增加趋势;HBVGN主要分布于～3岁组(71.4%),构成比随年龄增长而呈下降趋势。LN主要见于～18岁组,溶血尿毒综合征主要分布于～3岁和～6岁组。④原发性肾小球疾病主要病理类型：肾病综合征为微小病变/轻微病变(31.1%),急性肾炎为毛细血管内增生性肾小球肾炎(28.3%),慢性肾炎为硬化性肾炎(59.4%)。⑤2002至2012年肾病综合征、紫癜性肾炎、IgA肾病构成比较1989至2001年显著增高,急性肾炎、 HBVGN构成比显著下降。结论 肾活检患儿肾小球疾病临床和病理类型与年龄、性别有一定相关性,23年间某些肾小球疾病的构成比发生变化。     

儿童紫癜性肾炎临床与病理相关性分析

目的：通过对95例紫癜性肾炎（HSPN）患儿临床表现及肾脏病理分析,阐明其临床及病理之间的联系。方法：对HSPN患儿进行临床分型及病理分级,对其进行综合分析。结果：①临床分型以肾病综合征型(27.4%)、蛋白尿＋血尿型(24.2%)多见,病理分级以Ⅲb(42.1%)最多见;②尿检正常者可见肾脏病理改变。尿检正常型、孤立性血尿或蛋白尿型以及血尿和蛋白尿型病理改变差异无显著性(P>0.05);③孤立性血尿或蛋白尿型以及血尿和蛋白尿型病例,病程越长病理分级也越重(P＜0.05);④免疫复合物沉积以IgA+IgG+IgM（58%)同时存在比例最高;病理分级越重,病程越短,IgA+IgG+IgM比例越高。结论：HSPN患儿临床表现为肾病综合征和肾炎型者病理改变相对较重,临床症状与病理不一定平行,尿检正常者病理改变也很明显,病程越长,病理改变呈加重趋势。免疫复合物沉积为IgA+IgG+IgM的病理改变相对较重。［中国当代儿科杂志,2007,9（2）：129-132］     

Drugs controlling proteinuria of patients with Alport syndrome

Background

Proteinuria is one of the risk factors for the progression of renal diseases including Alport syndrome (AS), a hereditary glomerular renal disease. This study aimed to evaluate the efficacy of angiotensin converting enzyme inhibitors (ACEIs) and/or tripterygium, a Chinese herbal medicine widely used in Chinese patients with hematuria and proteinuria, on proteinuria in patients with AS.

Methods

Twenty-nine children were enrolled into this retrospective study. Patients were divided into 3 therapy groups: ACEI group, tripterygium group, and ACEI plus tripterygium group.

Results

In the 29 children, 23 were male and 6 female. In the ACEI group and the tripterygium group, the effective rate was 87.5% and 25.0%, respectively and in the ACEI plus tripterygium group was 42.9%.

Conclusions

ACEI is effective in controlling proteinuria of AS patients. Tripterygium should be carefully administered in controlling proteinuria of AS patients.     

Significance of family studies and kidney biopsies in children with renal hematuria

In children with renal hematuria the Alport syndrome could be diagnosed more frequently, if electronmicroscopic examination of the patients renal biopsy and a positive family history were obtained. In 16 children with renal hematuria, Alport syndrome was suspected by renal biopsy, physical examination or family history. Electronmicroscopic examination of the biopsy specimens of all 16 children revealed thinning together with a thickening and lamellation of the glomerular basement membrane (GBM), considered to be characteristic for Alport syndrome. In 11 of the children nephropathy, inner ear deafness or ocular changes were identified in 31 family members. In these families genetic information on the risk for other children is possible; furthermore ineffective medications such as steroids and cytotoxic drugs can be avoided, once the diagnosis has been established. In 5 children with characteristic renal lesions family history revealed no further support of Alport syndrome. In these cases with presence of characteristic lesions of GMB without positive family history the diagnosis Alport syndrome cannot be established with certainty, further examinations are necessary.     

COL4A5ͻ�� Alport�ۺ�����ͯ�ٴ����ͷ�������31�����棩

??Objective??To analyze the features of clinical manifestions and gene mutations of Chinesse children with X-linked Alport syndrome??XLAS??. Methods??Retrospectively analyze the clinical and pathological features of 31 patients with Alport syndrome with COL4A5 mutations??who were treated in Shanghai Children’s Hospital from June 2011 to June 2016. Results??Of these 31 cases??there were 12??38.7%?? females and 19??61.3%?? males??and the average age of onset was 2.6 years old. Thirteen patients had an onset of hematuria and proteinuria and 22??70.9%?? patients had family medical history. One patient presented ocular changes and 2 patients had hearing loss. Renal pathology showed that 15 of them had minimal change disease??MCD?? and 5 mesangial proliferative glomerulonephritis??and only 6 had typical pathologic changes of Alport syndrome. We identified 31 different mutations in all patients??and there were 19??61.3%?? cases of missense mutations??2??6.5%??cases of large deletion mutations??4??12.9%?? cases of spice-site mutations and 6??19.3%?? cases of frame shift mutations. Among these 19 missense mutations??16??84.2%?? cases were Gly-X-Y mutations. Conclusion??Most of XLAS children show MCD in renal biopsy and had missense mutations in COL4A5 gene. Clinical symptoms and pathology are not typical?? resulting in the difficulities in diagnosis of Alport syndrome.     

以激素耐药型肾病综合征起病的Alport综合征15例临床分析

目的 对以儿童激素耐药型肾病综合征(steroid-resistant nephrotic syndrome,SRNS)起病的Alport综合征(Alport syndrome,AS)的临床资料、病理和基因检测情况进行临床分析,以提高对AS的认识.方法 选取2015年1月至2019年12月广州医科大学附属广州市第一人民...     

基因诊断儿童Alport综合征30例临床分析

目的　探讨儿童Alport综合征（Alport syndrome,AS）的临床表型与基因突变检测的临床意义。方法　回顾性分析2013年1月至2017年6月在广州医科大学附属广州市第一人民医院儿科收治的30例基因突变患儿的资料。采集患儿及其家系成员的外周血样品,应用基因测序外显子序列捕获技术,寻找样品中是否存在Ⅳ型胶原α3链（COL4A3）、α4链（COL4A4）或α5链（COL4A5）三个突变基因,并对直系亲属行基因验证。结果　经过基因检测确诊Alport综合征（AS）30例,18例（60.00%）进行肾活检,光镜检查结果呈多样化,5例（16.67%）电镜检查表现为肾小球基底膜（glomerularbasementmembrane,GBM）弥漫性变薄、增厚和撕裂分层; 4例（13.33%）电镜表现为薄基底膜病（thin basement membrane nephropathy,TBMN）改变;免疫荧光检查3例（10.00%）肾组织Ⅳ型胶原α3、α5链阴性。22例患儿基因诊断X连锁显性遗传Alport syndrome （X-linked Alport syndrome,XL-AS）,发现8个COL4A5新突变位点。8例患儿基因诊断为常染色体隐性遗传（autosomal recessive Alport Syndrome,AR-AS）,发现3个COL4A4新突变位点。结论　儿童Alport综合征临床表现多样化,缺乏特异性,肾组织病理类型各异,难以早期诊断。基因检测有助于AS的早期诊断,判断患儿的预后,避免不必要的药物治疗。     

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??Objective??To investigate the clinical significance of the clinical phenotype and gene mutation detection in children with Alport syndrome. Methods??The data of 30 children with gene mutation admitted to Guangzhou First People’s Hospital??Guangzhou Medical University from January 2013 to June 2017 were retrospectively analyzed. Collect peripheral blood samples from children and their family members .Then use gene sequencing exon sequence capture technology to find out whether there was mutation gene??including ?? type collagen alpha 3 chain??COL4A3????alpha 4 chain??COL4A4?? or alpha 5 chain??COL4A5??. Gene mutations of related family members were identified by Sanger method. Results??The 30 children with AS were diagnosed by gene detection. Renal biopsy was performed in 18 cases??60.00%?? of 30 children with AS??and the results of light microscopy were various. Electron microscopic examination revealed diffuse thinning??thickening and delamination of the glomerular basement membrane??GBM?? in 5 cases??16.67%??. The electron microscopic examination showed thin basement membrane disease in 4 cases??13.33%??. Three cases??10.00%?? of immunofluorescence showed type ?? collagen alpha 3??alpha 5 chain negative in renal tissue. Totally 22 cases were diagnosed with X linkage dominant hereditary Alport syndrome??XL-AS?? by gene text??and 8 new mutation sites of COL4A5 were found. Genetic diagnosis showed 8 children were autosomal recessive inheritance??and 3 new COL4A4 mutations were found. Conclusion??The clinical manifestations of children with Alport syndrome are diverse and lack of specificity??and the pathological types of renal tissue are different. It is difficult to diagnose early. Gene detection helps to early diagnose of AS??to judge the prognosis of the children??and to avoid unnecessary drug treatment.