局灶硬化性肾小球肾炎的治疗

原发性局灶节段性肾小球硬化 (FSGS)由Rich在 195 7年首先描述[1 ] 。FSGS是一个病理形态学诊断名词 ,描述了组织学改变呈局灶、节段的病变特点 ,它既是特发性FSGS的定义 ,也是其它多种疾病 (高血压、病理性肥胖、获得性免疫缺陷病毒感染等 )发展到一定阶段的共同形态学改变。在过去的 2 0年中 ,FSGS的发生率明显增加。有资料显示 ,从 1974到 1993年 ,原发性FSGS的年发生率从 4%～ 10 %增加至 12 %～ 2 5 %。过去的经验认为原发性FSGS的治疗效果差 ,一般在发病 5～ 10年后进入至终末期肾功能衰竭(ESRF)。近年来发现其病因、发病…     

Takayasu arteritis: association with focal segmental glomerulosclerosis

We herein report on a 29-year-old woman who presented with edema and proteinuria. In light of her blood pressure differences and, finally, with the angiographic findings, Takayasu arteritis (TA) was the diagnosis. Renal biopsy showed focal segmental glomerulosclerosis (FSGS) and other possible etiologic alternatives were excluded. This was a very rare association and we could not find any other cases reported on TA accompanied with FSGS before. A poor treatment response was observed at the end of a 1-year therapy.     

Pembrolizumab-induced focal segmental glomerulosclerosis: A case report

Rationale:Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder that leads to end-stage kidney disease. Pembrolizumab, an immune checkpoint inhibitor, is an anti-programmed death 1 (PD-1) immunoglobulin G4 antibody approved for the treatment of advanced melanoma and can cause various renal immune-related adverse events (AEs), including acute kidney injury. Several cases of anti PD-1 therapy-induced glomerulonephritis have been reported so far, but FSGS has seldom been reported.Patient concerns:46-year old woman presented to our hospital with generalized edema.Diagnoses:Laboratory examination revealed features of nephrotic syndrome, and kidney biopsy confirmed FSGS. After other etiological factors of secondary FSGS were ruled out, she was diagnosed with FSGS caused by pembrolizumab.Interventions:She did not resume treatment with pembrolizumab and was treated with irbesartan and furosemide according to the American Society of Clinical Oncology Practice guidelines.Outcomes:After 2 months, the features of nephrotic syndrome resolved.Lessons:This case provides valuable insight into the etiology of FSGS that can occur as a renal immune-related AE of PD-1 inhibitor therapy. Therefore, patients should undergo evaluation for renal function and urinalysis at baseline and after treatment. If patients treated with PD-1 inhibitors present with renal injury and/or unexplained proteinuria >1 g/day, we would recommend a kidney biopsy to determine the underlying cause and establish an appropriate therapeutic plan.     

家族性局灶节段肾小球硬化症一家系临床与基因调查

目的:分析一个局灶节段性肾小球硬化症(FSGS)家系的临床特征,并对已知致病基因进行筛查。方法:调查1个中国汉族人FSGS家系,筛查其中78名成员后对可疑成员进行仔细临床检查。采集家系中67名成员的外周血样抽提基因组DNA,采用PCR扩增先证者NPHS2,ACTN4和TRPC6基因的所有外显子,寻找突变的方法对已知的家族性FSGS致病基因进行筛查。结果:该家系共有4代,103名成员,遗传方式为常染色体显性遗传。78名被调查家系成员中有11例患者和3例疑似患者迟发起病,平均发病年龄35.9岁。两例患者经肾活检证实为FSGS,其余患者均有不同程度蛋白尿,部分伴镜下血尿。家系先证者基因组DNA进行PCR逐个外显子扩增测序,未发现NPHS2、ACTN4、TRPC6三个已知的致病基因存在突变,发现SNP7个。结论:本家系是已报道最大的一个中国汉族人FSGS家系,符合常染色体显性遗传迟发起病型,家系内患者间临床表现存在明显差异。已知基因NPHS2、ACTN4、TRPC6不是该家系的致病基因。     

局灶节段性肾小球硬化研究的新方法、新观点

局灶节段性肾小球硬化(FSGS)是导致大量蛋白尿的一个常见病因,其中部分患者比较快地发展至终末期肾功能衰竭.尽管,有关FSGS不是一个均一的疾病已为人们所公认,但是,如何对其进一步在病因上进行诊断?怎样将不同的肾组织病理改变与临床表现加以结合?还存在许多尚不明了的问题.如果说对足细胞细胞生物学行为、足细胞损伤机制的研究,使我们对肾小球硬化的发生机制有了更深入的认识,那么,如何将这些基础研究应用于临床工作,也还有很大的距离.     

INF2基因在家族性局灶节段性肾小球硬化中的研究

新近发现INF2(inverted formin 2)基因是常染色体显性遗传性局灶节段性肾小球硬化的主要致病基因之一,编码成蛋白家族成员INF2蛋白.INF2蛋白作为一种重要的肌动蛋白成核因子,可促进球状肌动蛋白向纤维状激动蛋白的转换,及细胞微管骨架的形成.肾小球足细胞作为是一种终末分化的细胞,对细胞骨架高度敏感.INF2可通过多条通路的共同作用,最终破坏足细胞骨架的正常结构及足细胞特异性相关蛋白的表达而致病.     

局灶节段性肾小球硬化患者内皮细胞功能异常及临床意义

目的:前瞻性观察局灶节段性肾小球硬化(FSGS)患者的内皮细胞功能及其与疾病活动程度和并发症的关系。方法:63例经肾活检及临床确诊且蛋白尿≥3.5g/d的特发性FSGS患者进入本研究,选取年龄、性别相匹配的32例健康志愿者作对照。分析内皮细胞损伤指标循环内皮细胞计数(CECs)、血管性血友病因子(vWF)、可溶性血栓调节蛋白(sTM)、血管细胞粘附分子(VCAM)和E选择素(ES)的阳性率,观察起点内皮细胞损伤指标与其他临床指标及静脉血栓栓塞(VTE)并发症的关系,观察内皮细胞损伤指标的动态变化。结果:(1)FSGS患者的各项内皮细胞损伤指标均显著高于正常对照组。(2)无VTE的52例患者内皮细胞损伤指标的阳性率分别为CECs48.1%、vWF92.3%,sTM96.2%,VCAM67.3%,ES28.9%,其中VCAM阳性患者的血压水平、尿蛋白定量、血肌酐水平及肾小管损伤指标NAG酶、RBP均显著高于阴性者,CECs及ES阳性与阴性患者各项指标间无明显差异。相关性分析显示,sTM、VCAM与SCr显著正相关,VCAM、vWF与NAG、RBP均有正相关性。随访2月时15例达完全缓解(CR),13例部分缓解(PR),15例无效(NR),8例失随访,1例进入腹膜透析治疗退出本研究。CR组治疗后sTM、VCAM均明显下降,而vWF、ES水平变化不明显,PR组治疗前后相比sTM明显下降,余三项指标变化无统计学意义,NR组治疗前后各项内皮损伤指标均无明显变化。随访1年期间11例患者获得持续缓解,该组患者各观察点ES水平与正常对照组均无明显差异,sTM于随访2月时即降至正常,VCAM、vWF分别于随访2月、6月时开始下降,随访12月时仍高于正常对照。(3)合并VTE者CECs、vWF水平显著高于无VTE者。结论:FSGS患者存在明显内皮细胞功能异常,其中VCAM及CECs水平的异常升高分别与疾病的活动程度及血栓栓塞并发症的发生关系密切,随疾病的缓解内皮细胞功能得以不同程度的改善。内皮细胞损伤标志物的检测有助于对FSGS患者的病情及血栓栓塞并发症进行评估。     

Review on diagnosis and treatment of focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is one the most important causes of the nephrotic syndrome in adult patients. FSGS is not a disease entity. The identification of underlying causes of FSGS (secondary FSGS) has increased our insight into the pathogenesis of FSGS. Moreover, differentiating between primary (idiopathic) and secondary forms of FSGS is important to allow appropriate treatment. Recently a new pathological classification of FSGS was proposed, expanding FSGS to include nonsclerotic lesions. In this review we discuss the current diagnostic and therapeutic options in patients with FSGS.     

Effects of steroids in focal segmental glomerulosclerosis in a predominantly African-American population

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a common primary glomerulopathy in African Americans. Prolonged treatment with steroids is recommended for FSGS in those with nephrotic-range proteinuria, but strong evidence for this recommendation, especially in African-American adults, is lacking. We reviewed our experience with steroids in FSGS in a predominantly African-American cohort. METHODS: Patients with primary FSGS were identified and their charts were retrospectively reviewed for demographic data, characteristics of renal biopsy, blood pressure, and use of steroids. End-stage renal disease and doubling of creatinine were end-points. RESULTS: Seventy-two patients (65 African Americans) were identified with 48.3 months of follow-up. Patients receiving steroids (n=43) had higher urine protein excretion than those who did not. Seventeen patients reached end-stage renal disease and 26 doubled their creatinine concentration. Factors significant for renal survival on Cox proportional hazards model were initial creatinine level, severity of renal lesion, and blood pressure over the follow-up period. Treatment with steroids did not affect renal survival. About one third of patients receiving steroids developed complications consisting of diabetes (n=4) and greater than 5 kg weight gain (n=10). CONCLUSION: Renal function, severity of the renal lesion, and blood pressure determine renal survival in FSGS. A beneficial effect of steroids was not observed in this predominantly African-American adult cohort.     

Role of C3a and C5a in focal segmental glomerulosclerosis

<正>Objective To study the role of C3a and C5a in focal segmental glomerulosclerosis (FSGS) patients. Methods(1) A total of 66 patients with FSGS confirmed by renal biopsy were selected,including 18 cases of tip lesion,11 cases of perihilar,22 cases of not otherwise specified     

肾移植术后复发性局灶节段性肾小球硬化(附三例报道)

目的:探讨肾移植术后复发性局灶节段性肾小球硬化(FSGS)的临床病理特点及其转归,并与自体肾FSGS进行比较。方法:结合临床确诊的3例复发性FSGS的临床表现、病理特点及转归,回顾分析有自体肾、供肾和移植肾肾活检结果。结果:(1)自体肾FSGS的临床特点:3例患者自体肾FSGS的起病年龄分别为17岁(男)、23岁(女)、40岁(女),肾活检时尿蛋白定量分别为7.55g/24h,10.45g/24h,14.26g/24h,血清肌酐分别为99.0μmol/L、105.2μmol/L、265.2μmol/L。进展至ESRD的病程分别为4年、2年、4年。(2)自体肾FSGS的病理特点:3例患者球性/节段硬化的比例分别为5.3%/42.1%,0/6.9%,40%/33.3%,肾小管间质急性/慢性病变分别为0/10%、10%/0、10%/30%。例2和例3足突广泛性融合(50%)(例1未留取电镜组织)。例1和例3为细胞型,例2为顶部型,(3)复发性FSGS的临床特点:例1和例2分别于移植术后10d、40d出现蛋白尿(分别为18.27g/24h,7.55g/24h),病例3不详;并分别在移植后130d、67d、70d经肾活检确诊为FSGS,活检时尿蛋白定量分别为:10.13g/24h、15.8g/24h、4.38g/24h,血肌酐为114.0μmol/L、484.4μmol/L、701.8μmol/L。(4)复发性FSGS的病理特点及分型:早期仅表现为足突广泛融合,无节段硬化,重复活检出现节段硬化,并伴有明显的肾小管间质急性病变;例1和例3为细胞型,移植后复发仍为细胞型,例2为顶部型,术后复发时表现为塌陷型。(5)复发性FSGS的转归:例1行血浆置换,蛋白尿部分缓解,血肌酐上升缓慢,例2行免疫吸附治疗,效果不佳,3个月时移植肾功能丧失,例3失随访。结论:复发性FSGS患者临床亦表现为大量蛋白尿,并伴有肾功能不全,病理生理机制可能与自体肾脏病变有关;FSGS患者移植后早期出现蛋白尿时,应及时进行移植肾活检,光镜下可无肾小球节段硬化,但超微结果可表现为足突广泛融合,而重复肾活检则出现肾小球节段硬化;FSGS复发后其病理分型可以与自体肾相同,也可发生转变。     

成人激素抵抗的原发性局灶节段性肾小球硬化的评估和治疗

原发性局灶节段性肾小球硬化(famailial focal segmental glomerulosclerosis,FSGS)在1957年由Rich[1]首先描述,是一个病理形态学诊断名词,描述了组织学改变呈局灶、节段的病变特点,既是原发性FSGS的定义,也是其他多种疾病(高血压、病理性肥胖、获得性免疫缺陷病毒感染等)发展到一定     

成人特发性局灶节段性肾小球硬化的预后分析

目的:探讨成人特发性局灶节段性肾小球硬化的远期预后以及相关因素.方法:回顾性分析77例成人特发性局灶节段性肾小球硬化,估算Kaplan-Meier生存曲线,并就预后因素进行单因素和多因素COX回归分析.结果:77例患者平均随访(64.66±25.72)月.终末期肾病患者共17例,无人死亡.25例活检时合并急性肾衰竭的患者中7例进入终末期肾病.5年人、肾存活率分别为100%、83.8%,中位肾生存时间为(116±15.34)月(95%CI 85.93,146.07).单因素分析得出尿蛋白(HR 1.147,P＜0.01)、血肌酐(HR 3.233,P＜0.05)、小管间质慢性损伤(HR 1.684,P＜0.05)、治疗反应(HR 5.607,P＜0.01)与预后相关.多因素分析得出大量蛋白尿(HR1.327,P＜0.01)、小管间质慢性损伤(HR 2.161,P＜0.01)、治疗反应(HR 39.796,P＜0.01)为预后的独立危险因素.结论:中国成人特发性局灶节段性肾小球硬化的5年肾存活率为83.8%.大量蛋白尿、小管间质慢性损伤、治疗无效为预后的独立危险因素.     

Collapsing focal segmental glomerulosclerosis in a patient with oral cavity cancer: A case report

Rationale:Focal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases, leading to end-stage renal disease. Among the 5 variants of FSGS, the collapsing variant is rare and has the worst prognosis. Solid and hematologic malignancies are associated with glomerular diseases, such as membranous nephropathy, minimal change disease, and FSGS. However, squamous cell carcinoma of the oral cavity is rarely associated with nephrotic syndrome, especially FSGS.Patient concerns:A 55-year-old woman diagnosed with oral cavity cancer presented with generalized edema with heavy proteinuria and renal dysfunction after neoadjuvant chemotherapy and wide surgical excision.Diagnosis:Renal biopsy shows segmental or global collapse of glomerular capillaries with marked hyperplasia and swelling of overlying epithelial cells, suggesting a collapsing variant of FSGS.Interventions:After the renal biopsy, we prescribed oral prednisolone at a dose of 1 mg/kg/day. Despite immunosuppressive treatment, renal function deteriorated, and hemodialysis was started.Outcomes:After 23 sessions of hemodialysis and high-dose oral glucocorticoid treatment, renal function gradually improved, and oral glucocorticoid therapy was discontinued after 8 months. Currently, this patient is in a cancer-free state and has normal renal function without proteinuria.Lessons:Unusual collapsing FSGS might be associated with neoadjuvant chemotherapy and wide surgical excision in patients with oral cavity cancer. Proper diagnostic workup, such as renal biopsy and high-dose glucocorticoid therapy, might have helped recover from nephrotic syndrome and acute renal injury in cancer patients.