足细胞与局灶节段硬化性肾小球肾炎的研究进展

局灶节段性肾小球硬化(FSGS)由多种病因引起,临床主要以大量蛋白尿及肾病综合征为主要表现,病理表现为肾小球局灶节段性硬化。患者主要表现为蛋白尿,并逐步进展为慢性肾功能不全。FSGS早期已存在足突广泛融合、凋亡、脱落及损伤,表明足细胞是其发生、发展的主要目标细胞。该文将近年来关于足细胞与FSGS的研究进展予以综述。     

局灶性节段性肾小球硬化

局灶性节段性肾小球硬化(FSGS)是常见的一类原发性肾小球疾病,病变仅累及部分肾小球及肾小球毛细血管襻的部分小叶.局灶是指不足50%的肾小球受累及,而节段则指受累及的肾小球的1个或几个小叶受损.临床上以蛋白尿或肾病综合征为其主要表现,易于出现慢性进展性肾功能损害,终至慢性肾功能衰竭.而任何类型的肾小球疾病,随病情进展均可会有节段性乃至球性肾小球硬化.     

局灶节段肾小球硬化症的诊断与治疗

局灶节段肾小球硬化症(focal segmental glomerulose-erosis,FSGS)是一组临床及病理表现都具有特点的肾小球疾病.该病近年在世界范围内发病率有明显上升[1,2].本病临床以大量蛋白尿及肾病综合征为主要表现,病理呈现肾小球局灶节段性硬化.通常根据病因将其分为原发性和继烫发性两大类,本文重点讨论原发性FSGS的表现、治疗和预后.     

大剂量环磷酰胺与激素治疗局灶节段性肾小球硬化肾病综合征临床研究

目的:采用大剂量、长疗程环磷酰胺冲击联合激素治疗局灶节段性肾小球硬化肾病,观察其疗效。方法:17局灶节段性肾小球硬化肾病综合征患者,给予大剂量环磷酰胺冲击、足量泼尼松治疗5个月,并设立对照组,对结果进行分析,观察其疗效。结果:治疗组总有效率为82.35%,与对照组比较,差异有统计学意义(P<0.01)。结论:大剂量环磷酰胺与激素治疗局灶节段性肾小球硬化肾病临床疗效显著,但不良反应有所增加。     

肥胖相关性肾炎临床与病理探讨

目的 探讨肥胖相关性肾炎临床病理特点及临床表现。方法 回顾性分析3例肥胖相关性肾炎患者的临床表现，并对其肾活检组织进行光镜、免疫荧光观察及测量肾小球垂直直径。结果 3例肥胖相关性肾炎患者均存在蛋白尿，甚至肾病综合征，血清总胆固醇及甘油三酯升高。镜检可见肾小球体积明显增大或局灶节段性肾小球硬化。结论 肥胖相关性肾炎属少见肾病，患者临床常表现为蛋白尿、肾病综合征，肾小球体积明显增大或局灶节段性肾小球硬化是肥胖相关性肾炎特征性的形态学改变。     

阿霉素诱导单侧肾切除后大鼠肾小球硬化模型的实验研究

采用大鼠单侧肾切除后一次小剂量(3mg/kg)阿霉素尾静脉注射后造成肾小球硬化模型长达8个月的观察。结果表明:阿霉素注射3个月后出现大量蛋白尿和低蛋白血症、高胆固醇血症,无肾小球硬化。注射5个月后所有大鼠发展成为局灶性、节段性肾小球硬化。8个月后肾小球硬化更严重,伴有肾小管间质病变,其硬化率达49.90％。肾小球硬化率与尿蛋白呈正相关(r=0.97 P<0.01),与血清肌酐呈正相关(r=0.87 P<0.05)。认为阿霉素所诱导大鼠慢性进行性肾小球病变导致肾功能不全与人类的局灶性、节段性肾小球硬化病变相似。     

肾病综合征表现的局灶性节段性肾小球硬化的远期预后分析

本文将针对25年来治疗局灶性节段性肾小球硬化的一项区域性儿童肾脏病协作计划进行系统回顾.所有患儿经肾穿刺诊断为局灶性节段性肾小球硬化,其中大部分为美国黑人患儿,与之前报道的患同样疾病以白人为主体的患儿比较,他们的临床特点和远期预后均有不同.由于亚洲和非洲的肾病患儿局灶性节段性肾小球硬化的发生率均较高,因此中国患儿可能在疾病的临床特征、对治疗的反应和远期预后等方面与本文所讨论的美国黑人患儿类似.     

局灶性节段性肾小球硬化

局灶性节段性肾小球硬化(FSGS)是一常见的原发性肾小球疾病,常导致显著的肾功能不全及终末期肾功能衰竭。局灶性节段性肾小球硬化这一病理名称,由Arndd Rich于1957年首次提出,其损害主要发生在深部髓旁皮质,损伤特征是局部肾小球受损,大部     

转移因子治疗带状疱疹61例疗效观察

局灶性节段性肾小球硬化(FSGS)是常见的一类原发性肾小球疾病,病变仅累及部分肾小球及肾小球毛细血管襻的部分小叶。局灶是指不足50%的肾小球受累及,而节段则指受累及的肾小球的1个或几个小叶受损。临床上以蛋白尿或肾病综合征为其主要表现,易于出现慢性进展性肾功能损害,终至慢性肾功能衰竭。而任何类型的肾小球疾病,随病情进展均可会有节段性乃至球性肾小球硬化。1发病率FSGS是常见的肾小球疾病,约占原发性肾小球疾病的10%。主要累及男性,男女之比为1.2∶1,任何年龄均可发病,5岁以下小儿发病率可能更高。2病理改变FSGS特征性病理学损…     

辛通畅络疏利祛浊法治疗大鼠局灶性节段性肾小球硬化的研究

目的观察以辛通畅络、疏利祛浊法中药对大鼠局灶性节段性肾小球硬化的治疗作用及作用机制。方法采用2次阿奇霉素尾静脉注射方法复制局灶性节段性肾小球硬化模型,按体重均衡后随机分为正常组、模型组、治疗组(西药组、中药组),每组15只。各组动物于造模第9周末开始给药,西药组予贝那普利,中药组予辛通畅络疏利袪浊方药,连续8周。于实验的第1、4、8周末测大鼠24 h尿蛋白,血清白蛋白、肌酐、尿素氮含量,并进行光镜、电镜等观察。结果治疗组各项指标较模型组均有显著性差异,病理学观察也显示治疗组肾小球损伤均轻于模型组。结论中药组能够明显保护大鼠的肾功能,明显减轻模型组大鼠细胞外基质沉积,减轻肾小球硬化,延缓慢性肾脏病的进展。     

Molar pregnancy and glomerulonephritis

A 17-year-old, sexually active, single, nulliparous young woman presented to us with one week history suggestive of nephrotic syndrome. She was found to have a benign hydatidiform mole confirmed by histopathological examination after suction and curettage. Renal biopsy revealed focal segmental glomerulosclerosis. The renal pathology was most probably due to molar pregnancy due to the close temporal relationship. To our knowledge, this is the first case of focal segmental glomerulosclerosis associated with a gestation trophoblastic disease described in the literature.     

Remission of idiopathic nephrotic syndrome after treatment with cyclosporin A

Nephrotic syndrome in minimal change lipoid nephrosis and focal segmental glomerulosclerosis may be due to alteration of glomerular anionic sites by a lymphokine. Six adults with nephrotic syndrome who were resistant to treatment with corticosteroids and immunosuppressants were treated with cyclosporin A. In three patients with minimal change lipoid nephrosis who had been nephrotic for 3.5 to 23 years proteinuria resolved within 12 to 42 days. Subsequently, these patients became dependent on cyclosporin A. In three patients with focal segmental glomerulosclerosis who had been nephrotic for four to six years mean (SD) 24 hour urinary protein decreased from 14.7 (8.4) g to 3.6 (0.6) g within 20 to 25 days, serum albumin concentration rose, and oedema subsided. One patient died of myocardial infarction when still in partial remission after 11 weeks' treatment. Two patients remained proteinuric despite continuing treatment with cyclosporin A, but control of sodium balance was easy and serum albumin concentrations remained higher than without cyclosporin A. In all patients renal function improved during treatment. These preliminary results show that cyclosporin A may be effective in the treatment of patients with nephrotic syndrome that resists every other form of treatment and especially in the treatment of those with minimal change lipoid nephrosis. The results are in keeping with a T lymphocyte mediated mechanism of minimal change lipoid nephrosis and focal segmental glomerulosclerosis, but they also suggest that minimal change lipoid nephrosis and focal segmental glomerulosclerosis are separate entities.     

儿童单纯性血尿105例病理分析

目的 探讨小儿单纯性血尿的病理类型.方法 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%).结论 遗传性肾小球基底膜病占小儿单纯性血尿的第一位,但有明确家族史者不足50%.IgA肾病也是小儿单纯性血尿的主要原因之一,表现为单纯性血尿的IgA肾病病理变化相对较轻.部分单纯性血尿患儿肾小球未见明显病变.少数严重肾小球病变临床也可表现为单纯性血尿.     

Mitochondrial cytopathy presenting with focal segmental glomerulosclerosis, hypoparathyroidism, sensorineural deafness, and progressive neurological disease

A 6 year old boy who presented with steroid unresponsive nephrotic syndrome is reported. He was found to have focal segmental glomerulosclerosis and associated hypoparathyroidism and sensorineural deafness. The child progressed to end stage renal failure and was successfully managed by dialysis and cadaveric renal transplantation. He later developed progressive neurological deterioration and mitochondrial myopathy and neuropathy was diagnosed.     

A Rho-kinase inhibitor,fasudil, attenuates progressive glomerulosclerosis induced by daunorubicin in rats

Accumulating evidence suggests that the small G protein Rho and its downstream effec-tor Rho kinase may play important roles in kidney biology. The present study examined the effects of a Rho-kinase inhibitor, fasudil, on daunorubicin-induced progressive glomerulosclerosis and explored the underlying mechanism by which fasudil ameliorates glomerulosclerosis. Thirty-six male SD rats were randomly allocated into sham-operation group （sham group, n=12）, unilateral nephrectomy （UNX）＋daunorubicin （DRB） group （model group, n=12）, UNX＋DRB＋Fasudil group （treatment group, n=12）. Two to four weeks after the establishment of the animal model, 6 rats in each group were taken randomly for the detection of 24-h urine protein excretion. Kidney sections were exam-ined by HE and PAS staining, immunohistochemistry and transmission electric microscopy （TEM）. The expression of Rho-kinase mRNA and P27 mRNA in kidney were detected by RT-PCR. It was found that the 24-h urine protein excretion in model group was increased significantly as compared with sham group （P〈0.01）. But this increase was significantly suppressed by fasudil （P〈0.05）. At 4 week, the foot process effacement in podocytes, mesangial proliferation and ECM accumulation were observed in model group, presenting as focal segmental glomerulosclerosis. But in the treatment group, the fasudil alleviated glomerular injury, with proliferating cell nuclear antigen （PCNA）-positive cell infiltration ameliorated and the expression of P27 increased. The expression of Rho-kinase mRNA was significantly enhanced in model group and was suppressed in treatment group. Moreover, fasudil up-regulated the mRNA expression of P27. Our study demonstrated that the glomerulosclerosis was substantially ameliorated by inhibiting the expression of Rho-kinase. It is suggested that Rho-kinase pathway is involved in the renal injury and the inhibition of Rho-kinase may constitute a therapeutic strategy for the treatment of renal injury.     

肾小球硬化过程中转化生长因子受体基因获得性突变的研究

目的：探讨转化生长因子-βⅡ型受体基因（TβRⅡ）获得性突变在肾小球硬化中的作用。方法：选取32例局灶节段硬化性肾小球肾炎患者,利用肾小球微分离技术从肾活检组织切片分离出不同硬化程度的肾小球,一步法提取DNA,聚合酶链长度多态性法检测TβRⅡ基因中A10微卫星序列不稳定性。以突变条带积分像素密度（IPD）百分率和标准样品中DNA突变率作标准工作曲线。各样品突变条带IPD百分率通过标准曲线回归而得到各微分离小球TβRⅡ基因突变率。结果：肾活检组织切片经微分离获取的肾小球组织,一步法提取的DNA质量可靠,PCR一次成功率为87．5％;标准曲线中突变条带IPD百分率（10％、32％、55％、75％、88％）与DNA突变率（17％、24％、53％、79％、95％）相关性好（γ＝0．9908）。所有微分离肾小球组织均未能检出TβRⅡ基因获得性突变。结论：在肾小球硬化的形成过程中未能检测到TβRⅡ基因A10微卫星序列的突变。     

检测血、尿IgG4在特发性膜性肾病中的临床意义

目的： 探讨IgG4/IgG比值作为反映特发性膜性肾病病情活动和治疗预后的生物学指标的可能性。方法：收集40例特发性膜性肾病、16例微小病变和10例局灶节段性肾小球硬化患者肾活检当天的血和尿标本,以32例健康志愿者的血和尿作为对照组。IgG和IgG4的测定均采用夹心酶联免疫吸附法,IgG4/IgG由IgG4的浓度除以IgG的浓度得出。结果：特发性膜性肾病患者血和尿IgG4/IgG比值分别显著高于微小病变和局灶节段性肾小球硬化患者（P均<0.05）;特发性膜性肾病中,肾病综合征患者血和尿IgG4/IgG均高于非肾病水平蛋白尿患者（P=0.063,P<0.05）,缓解后患者血和尿IgG4/IgG均较治疗前显著降低(P<0.05）,而未缓解患者与治疗前比较,该比值无显著下降,甚至反而升高。24例随访患者中,2年随访期内复发患者的尿IgG4/IgG显著高于未复发者(P<0.05),肾活检时尿IgG4/IgG≥9%的患者有较高的复发趋势(P=0.071)。结论： IgG4/IgG比值可能有望作为反映特发性膜性肾病病情活动和治疗预后的生物学指标之一。     

Ten-year review of disease pattern from percutaneous renal biopsy: an experience from a paediatric tertiary renal centre in Hong Kong

OBJECTIVE: To study the childhood renal disease pattern based on the renal biopsy histology in a local paediatric tertiary renal centre. DESIGN: Retrospective study. SETTING: Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong. PATIENTS: All patients who underwent real-time ultrasound-guided closed renal biopsy from 1 April 1997 to 31 March 2007 were included. RESULTS: A total of 209 renal biopsies were performed, 162 on native kidneys and 47 on grafts. In the native group, major indications were renal manifestations secondary to systemic diseases (34%), followed by idiopathic nephrotic syndrome (28%) and haematuria (27%). In 94% the histopathology revealed glomerular diseases. Among the primary glomerular diseases, thin glomerular basement membrane disease, immunoglobulin A nephropathy, minimal change disease, and focal segmental glomerulosclerosis accounted for most. In all, 37% of patients with steroid-resistant nephrotic syndrome had focal segmental glomerulosclerosis and its relative incidence was increased when compared to previous studies. Minimal change disease and minimal change disease with mesangial immunoglobulin M deposits accounted for the majority of steroid dependent and frequent relapsers. Among patients with isolated microscopic haematuria, 73% had thin glomerular basement membrane disease, while patients with concomitant haematuria and proteinuria had a wide variety of pathology. In the kidney graft group, acute graft dysfunction was due to acute rejection in 38% of the patients, followed by calcineurin inhibitor toxicity in 14%. Chronic allograft nephropathy caused chronic allograft dysfunction in the majority of cases. Post-transplant proteinuria was caused by recurrence of the primary renal disease in all of our patients. CONCLUSION: This study provides updated epidemiological information for childhood renal disease and a change in the pattern of disease was observed.     

局灶节段性肾小球硬化对特发性膜性肾病患者预后的影响

目的探讨局灶节段性肾小球硬化(FSGS)对特发性膜性肾病(IMN)患者预后的影响。方法回顾性分析54例IMN患者的临床资料,根据是否伴有FSGS,将其分为伴FSGS组(FSGS+组)28例和不伴FSGS组(FSGS-组)26例。分析两组患者的临床病理特点和预后的差异。结果在肾活检前,FSGS+组的病程、血肌酐水平和高血压发生率高于FSGS-组,两组比较差异有统计学意义(P<0.05)。两组肾脏存活率比较差异无统计学意义(P>0.05)。结论 IMN患者常伴有FSGS样改变,FSGS可能不是肾脏死亡的危险因素。     

足细胞病的发病机制研究进展

足细胞是位于肾小球基底膜外部（GBM）的终末分化细胞,其形成的裂孔膜是肾小球滤过的最后屏障。足细胞损伤后,其结构完整性受损,足突消失,滤过膜孔径增大或断裂,大分子蛋白质滤出,超出近端肾小管重吸收能力而形成蛋白尿。研究表明,原发性足细胞病是以足细胞结构和功能异常为主要特点的肾小球疾病。本文主要对原发性足细胞病的几种类型,包括膜性肾病（MN）、微小病变型肾病（MCN）和局灶节段性肾小球硬化（FSGS）与足细胞的关系及其发病机制作一概述。