局灶节段性肾小球硬化(FSGS)的诊断和治疗进展

FSGS主要表现为大量蛋白尿或肾病综合征,近年来已成为肾病综合征最常见的病理类型,多数经过5-10年发展为终末期肾病.根据病因和发病机制,FSGS分为原发性和继发性两大类,继发性FSGS是指多种病因和发病机制明确的肾小球疾病所导致的肾小球局灶节段性硬化性病变,而原发性FSGS则发病原因不明,其发病机制日前认为与复杂的遗传因素、血流动力学改变、高脂血症和脂质过氧化、循环因子、病毒感染、细胞凋亡、足细胞损伤以及细胞外基质的合成与降解失衡、细胞因子等介导的免疫损伤都有密切关系.本文就其近年的诊断和治疗进展进行综述.     

CD2AP在局灶节段肾小球硬化症中的研究进展

CA2AP是位于足细胞及裂孔隔膜的蛋白分子之一,近期研究认为其同局灶节段肾小球硬化症密切相关,本文就近年来CD2AP与局灶节段肾小球硬化症的相关研究进展作一综述,以对临床防治FSGS提供一定理论依据.     

局灶节段性肾小球硬化相关基因研究进展

综述与局灶节段性肾小球硬化发病有关的相关基因研究的新进展。家族性FSGS的致病基因包括：NPHS1，NPHS2，ACTN4，CD2AP(鼠)。散发性FSGS致病基因mtDNA3243A→G突变，NPHS2，PON1等。     

局灶节段性肾小球硬化症诊治进展

局灶节段性肾小球硬化（FSGS）表现为蛋白尿,同时伴局灶节段性肾小球硬化和足突的消失。疾病早期,仅部分肾小球（〈50％）和毛细血管襻（（50％）出现硬化性改变。随着病变进展,肾小球逐渐出现球性硬化。根据病因可分为原发（特发）性、继发性FSGS两类,本文就原发性FSGS的诊治进展作一综述。     

局灶节段性肾小球硬化的临床和研究现状

局灶节段性肾小球硬化(FSGS)近年来发病率增加,是导致终末肾疾病的主要原因之一。本文简要叙述其在流行病学、发病机理、遗传学、形态学和治疗方面的一些进展。     

局灶节段性肾小球硬化相关基因研究进展

综述与局灶节段性肾小球硬化发病有关的相关基因研究的新进展。家族性FSGS的致病基因包括 :NPHS1,NPHS2 ,ACTN4,CD2AP(鼠 )。散发性FSGS致病基因mtDNA3 2 43A→G突变 ,NPHS2 ,PON1等。     

原发性局灶节段性肾小球硬化症的治疗

原发性局灶节段性肾小球硬化症（FSGS）是较常见的慢性肾小球疾病，占我国成人原发性肾小球疾病的9％，患者常以大量蛋白尿起病，常伴有镜下血尿、肾小管功能受损、高血压和肾功能不全，很容易发展成终末期肾衰竭。大量蛋白尿、低白蛋白血症、高脂血症和严重水肿使患者更易患感染、深静脉血栓形成等并发症，这些并发症不仅给治疗带来困难，也是加速肾功能恶化甚至直接导致死亡的主要原因。     

原发性局灶节段性肾小球硬化症治疗概况

原发性局灶节段性肾小球硬化（focal,segmental glomemloscterosis，FSGS）是一组具有类似病理特征的症候群，为儿童及成人多种肾脏疾病持续进展至终末期肾病最多见的病理改变，也是肾移植后复发的最常见原因。1957年Dr．Rich首次描述了此种病理变化，其后许多学者纷纷开始研究FSGS。     

原发性局灶节段性肾小球硬化患者CD2AP基因突变的研究

目的了解原发性局灶节段性肾小球硬化（FSGS）患者CD2AP基因突变特点。方法研究对象为2001年至2004年我院收治的82例病理确诊为FSGS患者，年龄12-76岁，男性43例，女性39例，临床诊断为肾病综合征（NS）者55例，非NS27例；60例健康正常人为对照组。外周血基因组DNAPCR扩增后直接测序。冰冻切片免疫荧光双染色，激光共聚焦显微镜采集图像检测突变患者肾组织中CD2AP和podocin蛋白的表达。结果（1）发现2个CD2AP外显子突变，1个为2号外显子160G〉A杂合突变，造成第54位氨基酸由缬氨酸变为异亮氨酸（V54I），该患者为非NS患者，已出现肾功能不全。另1个为4号外显子358A〉G杂合突变，造成第120位氨基酸由异亮氨酸变为缬氨酸（1120V），该患者为NS患者，曾复发2次，目前肾功能尚正常。正常对照120条染色体中未发现同样突变。查阅文献和基因库，未发现相同突变报道。（2）CD2AP外显子突变患者肾小球内CD2AP表达明显减低，同时伴有podocin表达的降低。（3）发现1个启动子区突变、2个内含子突变和8个SNP位点，其中一个单核苷酸多态性（SNP）位点以往未见报道。结论CD2AP突变可能是原发性FSGS的致病原因之一。CD2AP外显子突变可导致CD2AP蛋白表达减少，并影响podocin的表达。     

局灶节段性肾小球硬化症的病理诊断及分型

局灶节段性肾小球硬化症(focal segmental glomerulosclelrosis，FSGS)是一种临床和病理均具特点的肾小球疾病，临床以大量蛋白尿或肾病综合征为特征．病理以局灶和节段分布的硬化性病变为主要变化。根据病因发病机制分为原发性和继发性FSGS两大类，继发性FSGS是指多种病因和发病机制明确的肾小球疾病所导致的局灶肾小球的节段硬化性病变．而原发性FSGS则在病因、发病机制、病变特点、临床表现和预后诸方面均具特点的肾小球疾病，是本文讨论的重点。     

Adrenocorticotropic Hormone in the Treatment of Focal Segmental Glomerulosclerosis Following Kidney Transplantation

This retrospective study examined the effect of adrenocorticotropic hormone therapy on remission of recurrent focal segmental glomerulosclerosis (FSGS) in patients with history of kidney transplant (KT) treated at 2 transplant centers. Patients with biopsy-confirmed FSGS following KT who received Acthar Gel (Mallinckrodt ARD, Bedminster, New Jersey, United States) treatment for ≥1 month were eligible. A total of 14 patients with idiopathic FSGS were included. Acthar Gel treatment resulted in complete remission of FSGS in 3 patients and partial remission in 2 patients for a total treatment response rate of 36% (5/14) of patients. Among patients showing complete or partial remission, Acthar Gel treatment duration ranged from 6 months to 2 years and 60% (3/5 patients) had serum creatinine ≤ 2 mg/dL at the start of Acthar Gel treatment. Patient outcomes suggest Acthar Gel may be an effective and tolerable treatment for recurrent FSGS in patients with history of KT. Early initiation of Acthar Gel treatment and therapy duration of at least 6 months may be needed for optimal response to Acthar Gel in patients with history of KT and recurrent FSGS.     

Successful Treatment of Focal Segmental Glomerulosclerosis in Association with Mantle Cell Lymphoma

We have examined the role of reactive oxygen metabolites (ROM) in gentamicin nephrotoxicity and in glycerol-induced acute renal failure, a model for myoglobinuric acute renal failure. Several agents which affect mitochondrial respiration have been shown to enhance the generation of hydrogen peroxide. Based on gentamicin s ability to alter mitochondrial respiration both in vitro and in vivo we postulated that gentamicin may enhance the generation of ROM by renal com'cal mitochondria. Gentamicin, in a dose-dependent farhion, enhanced hydrogen peroxide production by rat renal cortical mitochondria as measured by the decrease in scopoletin jluorescence. At the highest concentration of gentamicin tested (4.0 mM), the rate of hydrogen peroxide generation w s markedly increased from 0. I7 f 0.02 to 6.21 f 0.67 nmol/mg/m*n. We next demonstrated that hydroxyl radical scavengers and an iron chelator provide a marked functional and histological protection in gentamicin-induced acute renal failure in rats. Hydroxyl radical scavengers and the iron chelator deferoxamine also protected renal function in glycerol-injected rats, a model for acute renal failure due to muscle injury. Although these data suggest that ROM may be important mediators of toxic renal injury, in vivo generation of ROM by kidney in normal and pathological states has not been previously examined. Aminotriazole (An irreversibly inactivates catalase only in the presence of hydrogen peroxide and previous studies have shown that AT-medated inhibition of catalase in a sensitive measure of in vivo changes in the hydrogen peroxide generation. Using this method, we have demonstrated the in vivo generation of hydrogen peroxide under normal conditions and enhanced generation of hydrogen peroxide in rats treated with gentamicin or glycerol. Finally, in in vitro studies we have shown that iron and intracellular calcium play a critical role in hydrogen peroxide-mediated cytotoxicity to LLC-PK, cells, a renal tubular epithelial cell line. Taken together our data provide evidence for a role of ROM in gentamicin and glycerol-induced acute renal failure and provide evidence for the role of iron and calcium in oxidant injury to renal tubular epithelial cells.     

Focal Segmental Glomerulosclerosis Associated with Idiopathic Myelofibrosis

A patient with idiopathic myelofibrosis with nephrotic syndrome is reported. Seven months after the initial diagnosis of myelofibrosis, the patient was presented with dyspnea, generalized edema, heavy proteinuria, massive pleural effusion, and ascites. Renal biopsy showed focal segmental glomerulosclerosis. After starting immunosuppressive therapy consisting of cyclosporine and steroids, his renal function and proteinuria improved and transfusion requirements decreased.     

原发性局灶节段性肾小球硬化的中西医结合个体化治疗的疗效观察

目的 :研究中西医结合个体化治疗原发性局灶节段性肾小球硬化 (pFSGS)的疗效。方法 :对 30例经肾活检术确诊为 pFSGS的患者根据不同个体采用中西医结合个体化治疗方案 ,供选择药物有 :强的松 (Pred)、雷公藤多甙片 (T1)、血管紧张素转换酶抑制剂 (ACEI)、环磷酰胺 (CTX)、非甾体类消炎药 (NsAID)、益肾通络方 (黄芪、首乌、金樱子、积雪草、桃仁、制军 )等。以 15例未按上述正规治疗的患者作对照。结果 :治疗观察 (33.5 8± 2 0 .6 7)月 ,治疗组完全缓解 16例 (5 3.33% ) ,显效 8例 (2 6 .6 7% ) ,有效 5例 (16 .6 7% ) ,无效 1例 (3.33% ) ,其中 10例肾衰竭的患者 ,治后 8例恢复正常。对照组未见临床缓解或显效 ,仅 7例有效 ,差异显著 (P <0 .0 1)。结论 :中西医结合个体化治疗pFSGS的疗效明显优于对照组