IgA肾病肾病综合征临床病理特点及肾脏病理危险因素

目的：探讨IgA肾病肾病综合征患者临床病理特点及肾脏病理损害的危险因素。方法：选择1987年～2006年经肾活检确诊IgA肾病并表现为肾病综合征的患者118例，分析其临床病理特点，按肾脏病变轻重分为A组（n=34，包括Lee氏分级Ⅰ级、Ⅱ级）、B组（n=84，Ⅲ、Ⅳ、Ⅴ级），比较两组临床指标，并多因素分析影响肾脏病理损害的危险因素。结果：A、B两组高血压分别占11．8％ vs 63．1％；肾衰竭分别占15％ vs 41．7％；A、B两组尿蛋白≥6g／24h者分别占58．8％ vs 32．1％；尿红细胞满视野分别为14．7％ vs 50％。A组高血压、肾衰竭、镜下尿红细胞满视野发生率显著低于B组（P〈0．01），尿蛋白≥6g／24h发生率显著高于B组（P〈0．01）。A组平均动脉压、血肌酐明显低于B组（P〈0．01）；而尿蛋白定量、血红蛋白显著高于B组（P〈0．05）。多因素分析显示IgA肾病肾病综合征患者肾脏病理损害重的危险因素有平均动脉压、尿蛋白〈6g／24h、镜下尿RBC〉5．0×10^7／L（0R值分别为1．048，3．227，6．578；P值分别为0．034，0．047，0．002），血红蛋白是保护性因素（OR=0.723，P=0．035）。随着平均动脉压的升高、血红蛋白的降低、镜下尿红细胞数的增多，肾脏病理损害程度加重（P〈0．01）。结论：IgA肾病肾病综合征患者临床、病理表现存在差异，高血压、血红蛋白水平、24h尿蛋白排泄量、镜下尿红细胞程度有助于判断肾脏病理损害轻重。     

肌球蛋白重链9基因单核苷酸多态性与内蒙古自治区汉族IgA肾病临床、病理及预后的关系

目的 探讨肌球蛋白重链(MYH)9基因单核苷酸多态性与内蒙古自治区汉族IgA肾病患者临床特征、病理及预后的关系.方法 以经肾组织活检确诊的IgA肾病患者148例为研究对象,对其中56例患者进行了1～97月的随访.取外周血提取DNA,采用PCR限制性片段长度多态性分析(RFLP)法检测MYH9基因Rs3752462、Rs4821480位点单核苷酸多态性.研究各位点基因型与IgA肾病患者临床特征的相关性.分析不同基因型与疾病进展和预后的关系.结果 (1)Rs3752462位点符合Hardy-Weinberg平衡,Rs4821480位点不符合Hardy-Weinberg平衡.(2)IgA肾病患者MYH9基因Rs3752462位点TT基因型患者的收缩压低于CC+CT基因型(P＜0.05).Rs4821480位点GG基因型与TT+GT基因型两组患者收缩压、舒张压、年龄差异有统计学意义(P＜0.05).Scr、肌酐清除率、血白蛋白、血红蛋白、镜下血尿、蛋白尿程度等临床指标及病理HASS分级、肾病理改变在Rs4821480位点、Rs3752462位点3种基因型组间差异无统计学意义.(3) Kaplan-Meier生存分析提示Rs3752462位点CC基因型、Rs4821480位点TT基因型患者肾活检到肾功能减退时间显著较短(P＜0.05).结论 MYH9基因Rs3752462位点C等位基因是引起IgA肾病患者高血压损害的独立危险因素.MYH9基因Rs4821480位点3种基因型多态性与患者预后相关.携带Rs3752462位点C等位基因、Rs4821480位点T等位基因可能影响患者的预后.     

Tacrolimus对糖尿病大鼠肾脏足细胞损伤的保护作用及机制

目的探讨Tacrolimus（FK506）是否通过足细胞的保护作用减轻糖尿病大鼠尿白蛋白排泄。方法将40只大鼠按随机数表法分为对照组（C组）、糖尿病（diabetesmellitus,DM）模型组（DM组）、DM＋FKS060．5mg·kg^-1·d^-1给药组（FK5060．5组）及DM＋FK5061．0mg·kg^-1·d^-1给药组（FK5061．0组）,每组10只。采用链脲佐菌素（streptozotocin,STZ）腹腔注射建立糖尿病模型,FK506灌胃给药。4周后大鼠24h尿白蛋白测定采用酶联免疫方法,电镜下观察肾小球足细胞病理组织学改变,应用免疫荧光与Westernblot检测肾组织Nephrin和Podocin表达。结果DM组大鼠24h尿白蛋白排泄率（albuminexcretionrate,AER）明显高于对照组（P〈0．01）,FK5060．5与1．0mg／kg给药组大鼠AER水平明显低于模型组（P〈0．05,P〈0．01）。透射电镜观察DM组肾小球基底膜增厚、结构模糊不清,系膜基质增多,足细胞损伤,与DM组比较,FK5060．5、1．0组肾组织超微结构改变有不同程度改善。免疫荧光显示Nephrin和Podocin在C组大鼠肾小球呈线状均匀分布;DM组大鼠肾小球表达明显减少,且呈颗粒状不均匀分布;FK5060．5组和FK5061．0组Nephrin和Podocin表达不同程度增加,呈线状及颗粒状分布。Westernblot显示DM组Nephrin和Podocin较C组表达明显下降;FK5060．5组和FK5061．0组Nephrin和Podocin量较DM组明显增加（P〈0．01）。结论FK506能减少糖尿病大鼠尿白蛋白排泄,改善肾小球足细胞病变,其机制可能与上调Nephrin和Podocin表达有关。     

Nephrin和WT1在原发性肾病综合征患者肾小球的表达及意义

目的探讨原发肾病综合征（NS）患者肾小球足细胞中裂孔隔膜蛋白nephrin、Wilm肿瘤蛋白1（WTl）的表达及分布特征。方法选择肾病综合患者80例（NS组）,根据其病理诊断水平分为微小病变（MCN）组、IgA肾病组、膜性肾病（MN）组、局灶节段性肾小球硬化（FSGS）组,每组20例;另设正常对照组10名。采用免疫组织化学方法检测各组肾小球nephrin、WT1的表达指数（EI）,并进行组间比较。结果①正常对照组nephrin在肾小球毛细血管壁,呈均匀、线状分布;肾病综合征组患者nephrin在肾小球中分布不均,部分区域染色明显减弱,部分区域线性消失,呈颗粒状或者团块状。MN组和IgA肾病组与正常对照组比较显著降低（P〈0．05）。nephrin的表达水平与24h尿蛋白定量呈负相关（r=-0．216,P〈0．05）,与白蛋白呈正相关（r=0．300,P〈O．01）。②WT1在肾小球足细胞胞核内表达。MCN组、IgA肾病组及FSGS组与正常对照组比较表达下降（P〈0．05）。WT1的表达与24h尿蛋白定量呈负相关（r=-0．304,P〈0．05）,与血浆白蛋白呈正相关（r=0．338,P〈0．01）。结论NS早期即可出现肾小球足细胞中nephrin、WT1的表达和分布减少,而且随着病变的加重,这种变化愈发明显。足细胞病不仅导致大量蛋白尿发生,而且还可能与肾小球硬化的发生有关。     

青少年布加综合征临床特点及介入治疗

目的 探讨青少年布加综合征(Budd-Chiari syndrome,BCS)临床特点并评估介入治疗的疗效.方法 徐州医学院附属医院自1990年1月至2012年4月收治227例年龄在29岁以下的BCS患者,均经彩超及血管造影证实,其中下腔静脉型87例、肝静脉型105例、混合型35例.通过经皮血管腔内血管成形术(percutaneous transluminal angioplasty,PTA)、血管内支架置入术及置管溶栓术开通闭塞血管.术后给予抗凝治疗、定期随访.结果 227例患者均以门脉高压的症状和体征为最初临床表现.210例患者初次介入手术取得成功,其中下腔静脉阻塞型成功率100％,肝静脉阻塞型85.7％,混合型94.3％.介入治疗成功后的下腔静脉平均压力由术前的(26.52±8.16) cm H2O下降至术后(14.28 ±4.08) cm H2O(P＜0.05).肝静脉平均压力由术前(35.70±13.26) cm H2O下降至术后(18.36±8.16) cm H2O(P＜0.05).术后随访1个月至15年,平均(46±37)个月.再狭窄发生率为21.4％(45/210),其中下腔静脉型狭窄率为13.8％(12/87),肝静脉阻塞型31.1％ (28/90),混合型15.2％ (5/33),肝静脉型患者再狭窄发生率明显高于其他两型.再狭窄患者介入治疗方法同初次治疗,44例再狭窄患者再次介入治疗取得成功.结论 青少年布加综合征患者以肝静脉阻塞型最多见,门脉高压症状和体征为主要临床表现特点,肝静脉型介入治疗后复发率高于其他两型.     

癌组织K-ras基因突变、术前血清CEA水平与结直肠癌临床病理特点的关系

目的观察结直肠癌组织中K-ras基因突变情况,术前检测患者血清CEA水平,探讨两者与结直肠癌临床病理的关系。方法应用实时荧光定量PCR方法和基因测序技术检测100例结直肠癌组织中K-ras基因12、13密码子突变情况,化学发光法检测患者血清CEA水平,结合其临床病理资料进行统计学分析。结果 K-ras基因突变者39例(39.0%),其中12号密码子突变31例,13号密码子突变8例。有淋巴结转移者K-ras基因突变率(57.8%)明显高于无淋巴结转移者(23.6%),有肝脏转移者K-ras基因突变率(62.5%)明显高于无肝转移者(34.5%),TNM分期Ⅲ、Ⅳ期K-ras基因突变率(56.5%)明显高于Ⅰ、Ⅱ期(24.1%)。K-ras基因突变率与肿瘤大小、部位、肿瘤浸润深度、分化程度无密切关系。49例CEA水平超出正常范围(49.0%)。有淋巴结转移或肝转移患者CEA水平显著高于无淋巴结或肝转移患者(P0.05)。在肿瘤不同的临床病理分期(Duke's、TNM分期)间CEA水平差异有统计学意义,Duke's D期和TNMⅢ、Ⅳ期出现高阳性率。CEA水平在肿瘤不同浸润深度、体积及分化程度上无明显差异。结论癌组织K-ras基因突变和血清CEA水平超出正常水平预示结直肠癌可能合并淋巴结转移或肝转移,是预后不良的指标。     

糖尿病肾脏疾病足细胞损伤机制及中医药干预研究进展

糖尿病肾脏疾病(diabetic kidney disease,DKD)是慢性肾脏病和终末期肾病的首要病因,发病机制尚不明确.足细胞损伤在DKD发生和发展过程中有关键性作用.本文从的代谢紊乱、氧化应激、炎症反应、自噬失调方面综述DKD足细胞损伤机制,以及中药干预的靶点和途径,为中药防治DKD研究提供新的思路与借鉴.     

Von Hippel-Lindau 综合征累及肾脏、胰腺及肾上腺的CT 表现

目的 总结Von Hippel-Lindau syndrome(VHL 综合征)累及肾脏、胰腺及肾上腺的CT表现,以提高对本病的认识.方法 收集临床符合VHL 综合征诊断标准且有腹部受累的病例9 例,回顾性分析其临床、病理资料及多层螺旋CT(MSCT)表现.9 例全部行MSCT 平扫及增强检查.结果 9 例均有双肾多发病变,分为3 种类型:单纯性囊肿、囊实性肿块和实性肿块,其中6例3 种类型病灶混合存在,3 例仅有双肾多发单纯性囊肿.3 例行肾肿块切除,术后病理为透明细胞癌.7 例胰腺可见多发囊肿,其中4 例囊壁见钙化,1 例合并胰岛细胞瘤.3 例肾上腺可见嗜铬细胞瘤,2 例为双侧.5 例具有家族遗传史.结论 VHL 综合征可累及腹部多个器官,表现复杂多样,熟悉掌握其MSCT 表现有利于疾病的早期、全面诊断.     

挤压综合征急性肾功能衰竭的发病机制及研究进展

挤压综合征是一种少见而凶险的疾病.多由地震、矿井塌方、车祸等外界物体压迫躯体引起.随着对此病认识的逐步提高,有关其发病机制的研究越来越多.地震、车祸造成的挤压综合征,其导致死亡原因多认为是肾功能衰竭.我们从肾小管内管型形成、肌红蛋白对肾小管的直接毒性、肾血管痉挛、低血容量休克、缺血再灌注损伤和细胞因子等方面阐述挤压综合征急性肾功能衰竭的发病机制及研究进展.     

Alport综合征临床病理研究及基底膜Ⅳ型胶原检测

目的分析研究Alport综合征(AS)临床、病理特点及基底膜Ⅳ型胶原的变化.方法对本科1990.1～1996.6间发现的14例AS患者(12家系)进行调查,其中男11例,女3例,平均年龄29.4岁.结果 13例呈镜下血尿,7例伴发作性肉眼血尿.蛋白尿见于所有患者,3例为肾病综合征.进行性肾功能衰竭男性10例(11～39岁)女性1例(40岁).6例血透,其中接受肾移植2例.75%有听力下降,以双侧神经性耳聋为主.2例前锥形晶体.遗传呈异质性,以X伴性显性为主(6个家系).光镜改变以局灶节段硬化为主,免疫荧光多呈阴性,电镜呈弥漫肾小球基底膜(GBM)厚薄不均(所有标本)及分层网状(1例).4例XD-AS男性患者GBM及表皮基底膜(EBM)抗α3,4,5(Ⅳ)抗体间接免疫荧光均为阴性.结论 AS是一并不少见的以血尿、蛋白尿、进行性肾功能衰竭伴眼、耳改变为特征的遗传病,其基底膜存在Ⅳ型胶原异常,Ⅳ型胶原各α链的检测对AS有诊断意义.     

End-stage renal disease in two pediatric patients with Fechtner syndrome

Fechtner syndrome, a disease in the spectrum of the hereditary nephridites, is a macrothrombocytopenia associated with sensorineural hearing loss, cataracts, nephritis, and characteristic leukocyte inclusions. Renal biopsy findings are consistent with those of Alport syndrome, and the associated renal disease is said to be unusual before mid to late adulthood. Here, we review the available literature on this disease and report two African-American pediatric patients with Fechtner syndrome who rapidly progressed to end-stage renal disease during adolescence. We conclude that chronic renal failure can occur at a young age in patients with Fechtner syndrome, with a possible relation to race/ethnicity. Fechtner syndrome, or other variants of Alport syndrome, need to be considered in patients presenting with proteinuria and thrombocytopenia. Received: 13 July 1998 / Revised: 2 June 1999 / Accepted: 3 June 1999     

足细胞与Alport综合征蛋白尿的关系

目的 探讨足细胞与Alport综合征（AS）蛋白尿的关系。 方法 AS 患者21例,男13例,女8例,根据24 h尿蛋白量将患者分3组, 10例<30 mg/kg为轻度蛋白尿组, 4例30~50 mg/kg为中度蛋白尿组,7例>50 mg/kg为重度蛋白尿组。正常肾组织对照3例。电镜下根据平均足突宽度=л/4×（Σ基底膜长度/Σ足突个数）,计算每例患者足突宽度。分析足突宽度与蛋白尿关系。用免疫组化方法分析肾组织中裂孔隔膜分子nephrin、podocin和细胞骨架分子synaptopodin的表达。 结果 AS患者肾小球足细胞足突宽度（420~2270 nm）与24 h尿蛋白量呈正相关（r = 0.765,P < 0.01）。轻度蛋白尿组足突宽度[475（420~900 nm）]显著低于重度蛋白尿组[1520（480~2270） nm]（P < 0.05）。重度蛋白尿组患儿nephrin和podocin表达分布发生改变;表现为弥漫足突融合者synaptopodin表达分布发生改变。2例蛋白尿病程较短（1年）患儿无弥漫足突融合,synaptopodin分布正常,但nephrin和podocin分布异常。 结论 肾小球足细胞足突融合、裂孔隔膜及足细胞骨架分子参与AS患儿大量蛋白尿的发生,裂孔隔膜损伤似乎早于足细胞骨架改变。对蛋白尿早期干预可能有助于延缓疾病进展。     

Association between polymorphisms in non-muscle myosin heavy chain 9 gene and hypertension susceptibility in chronic kidney disease patients

Objective To explore the association between polymorphisms in non-muscle myosin heavy chain 9 gene (MYH9) and hypertension susceptibility in chronic kidney disease (CKD) patients. Methods Five hundred and ninety-five persons, including 301 patients with CKD and 294 healthy controls, were enrolled in the study. Two single nucleotide polymorphisms (SNPs) (rs3752462, rs4821480)were genotyped by TaqMan assay or a restriction fragment length polymorphism assay for a further case-control study. The discrepancies of the patients'quantitive traits (including age, sex, systolic and diastolic blood pressure, frequency of different primary diseases and using different kinds of antihypertensive drugs) among different genotypes of the two MYH9 SNPs were analyzed. Meanwhile,theassociation between polymorphisms in MYH9 and hypertension susceptibility in CKD patients were analyzed in the rs3752462 site. Results The systolic blood pressure of CT genotype patients[(147.94±27.40) mm Hg] was significantly higher than that of CC genotype patients [(136.43±19.09) mm Hg] by single factor analysis of variance (P＜0.05). The frequency of using all kinds of antihypertensive drugs for CC genotype patients (7.4%) was lower than that of TT (43.9%) and CT (48.7%) genotype patients (P＜0.05).After correcting the age factor, the result of Logistic regression analysis showed that CC genotype was a protective factor of systolic blood pressure increasing. The probability of high blood pressure for CT genotype patients with CKD was 0.175 times than that of CC genotype (95% CI 0.071,0.431). Conclusions The CKD patients who carry the rs3752462 site CC genotype of MYH9 gene are not prone to high blood pressure. Polymorphism of MYH9 gene rs3752462 site is associated with systolic blood pressure in CKD patients. It may indicate that allele C mutation for T can lead to the increase in systolic blood pressure.     

Pathogenesis of vascular anomalies

Vascular anomalies are localized defects of vascular development. Most of them occur sporadically (ie, there is no familial history of lesions, yet in a few cases clear inheritance is observed). These inherited forms are often characterized by multifocal lesions that are mainly small in size and increase in number with patients' age. The authors review the known (genetic) causes of vascular anomalies and call attention to the concept of Knudson's double-hit mechanism to explain incomplete penetrance and large clinical variation in expressivity observed in inherited vascular anomalies. The authors also discuss the identified pathophysiological pathways involved in vascular anomalies and how it has opened the doors toward a more refined classification of vascular anomalies and the development of animal models that can be tested for specific molecular therapies.     

The ivemark syndrome: prenatal diagnosis of an uncommon cystic renal lesion with heterogeneous associations

Renal dysplasia has been reported in association with a number of anatomical abnormalities, including pancreatic dysgenesis and hepatic anomalies. The combination of renal, hepatic, and pancreatic dysplasia (RHPD), also known as Ivemark syndrome, is rare and uniformly fatal. We report here the gross and histological findings in 4 cases of combined RHPD, 2 of which were detected by prenatal ultrasonography. Evaluation of these 4 and the other 20 reported cases shows that combined RHPD has considerable variability in the histological findings and in organ involvement. In addition, nearly half were associated with anomalies in other organ systems, and 11 of the 24 were familial. In this study, ultrasonographic and histological abnormalities were seen as early as 18.5 weeks gestation in 1 case.     

Klippel-Trenaunay-Weber综合征发病机制及治疗方案探讨

目的探讨Klippel-Trenaunay-Weber综合征(KTWS)的发病机制和分期综合治疗的可行性。方法1999年7月至2004年9月广东省人民医院和广州军区广州总医院对14例KTWS病人行患肢动脉造影,对不同的血管病变分别以平阳霉素+超液化碘油、PVA、NBCA、钢圈进行Ⅰ期血管内介入治疗,4周后再行Ⅱ期手术治疗,并观察其疗效。结果13例(13/14)病人术后症状消失,除增长、增粗的患肢未能恢复到健肢完全一致外,其余体征消失。随访12例,平均随访(26·5±9·3)个月,未见复发迹象。结论通过针对KTWS发病机制的分期综合治疗,可取得显著效果。     

Clinical features and HLXB9 gene mutation of a sporadic Chinese Currarino's syndrome case

Background/Purpose

The Currarino's syndrome (CS), which is characterized by sacral bony anomalies, anorectal malformation, and a presacral mass, is associated with mutations of HLXB9 gene. The aim of this study was to clearly define the clinical manifestations and molecular anomalies of CS in China.

Methods

We studied the medical history and clinical manifestations of a child with presacral mass. Genomic DNA was extracted from lymphocytes, and mutation analysis of the HLXB9 gene was conducted by using polymerase chain reaction and direct sequencing in the child and her parents.

Results

A previously unreported heterozygous missense mutation of HLXB9 gene was detected in the child.

Conclusions

The HLXB9 gene mutation could take place in sporadic cases of CS without a typical hemisacrum.     

经典型Bartter综合征家系CLCNKB基因突变分析

目的 研究一个经典型Bartter综合征家系CLCNKB基因突变情况。 方法 提取该家系各成员患者外周血淋巴细胞基因组DNA,应用PCR扩增CLCNKB基因全部外显子及侧翼序列,并直接测序检测突变。选取50例无亲缘关系的健康人作为对照。 结果 在患者中检测到1个杂合（错义）突变,其第4号外显子,第482位碱基T→G突变,造成第161位氨基酸由亮氨酸变为精氨酸（482T>G,L161R）;家系中母亲为杂合突变（L161R杂合突变）,父亲未发现突变;查阅国内外文献及人类基因突变数据库,L161R未见报道,属新发现的突变。 结论 发现了一种新的CLCNKB基因突变：L161R。