局灶节段性肾小球硬化诊治现状

局灶节段性肾小球硬化(FSGS)临床主要表现为蛋白尿和肾病综合征,病理以局灶节段分布的肾小球硬化及足细胞的足突融合为特征,是导致终末期肾脏病的主要原因之一。由于FSGS病因复杂,发病机制也尚未明确,其诊断及治疗还面临很多困难。文章综述近年来FSGS的诊治现状。     

儿童局灶节段性肾小球硬化

局灶节段性肾小球硬化（FSGS）近年来有增多趋势,FSGS不仅是一种形态学描述,而被视为一种临床病理综合征,表现为蛋白尿,常为肾病水平蛋白尿,并有局灶节段分布的肾小球硬化和足突融合。FSGS可为原发性（特发性）、继发性和遗传家族性。最近FSGS被区分为5种变异型,提示其不同的发病机制和预后,这5型包括特异FSGS、门周型、细胞型、顶端病变和塌陷型。该文还就FSCS的治疗和预后进行了讨论。     

局灶节段性肾小球硬化的流行病学进展

局灶节段性肾小球硬化(FSGS)是一种临床病理综合征,病理以局灶节段分布的肾小球硬化及足细胞的足突融合为特征;临床主要表现为大量蛋白尿和肾病综合征;多表现为激素耐药,且常进展成终末期肾病;是儿童时期进展为终末期肾病的主要疾病之一。近年来全球报道FSGS肾活检检出率呈增多趋势,文章综述FSGS的流行病学进展。     

原发性局灶节段性肾小球硬化的诊断与治疗策略

儿童局灶节段性肾小球硬化(FSGS)近年来有增多趋势,FSGS不仅是一种形态学描述,而且被视为一种临床病理综合征,多表现为肾病综合征,同时伴血尿和高血压,病变呈进行性,可继续发展为弥漫性硬化性肾小球肾炎,25%～30%的FSGS患儿5 a后进展至慢性肾衰竭,对激素治疗效果不理想。因此,早期诊断与及时治疗特别重要。现就原发性FSGS的诊断与治疗策略进行阐述。     

家族性局灶节段性肾小球硬化一家系报告及文献复习

目的 探讨家族性局灶节段性肾小球硬化（FFSGS）的临床特点、诊断、治疗及预后。方法 结合1个FFSGS家系临床资料进行文献复习,分析该病临床特点、诊断、鉴别诊断、发病机制、治疗及预后。结果 家谱分析可提示遗传类型;诊断主要依据病理,病理早期为局灶性、节段性改变,晚期为弥漫性、球性改变;免疫抑制治疗效果差。结论 FFSGS是一种罕见的遗传性疾病,预后差。     

局灶性节段性肾小球硬化

局灶性节段性肾小球硬化(FSGS)是病理学诊断名称,它具有特殊病理学变化及临床表现。该病发病率逐渐增多,在儿童肾病综合征(NS)中,仅次于微小病变型(MCD),在难治性肾病综合征中也占有重要地位。FSGS在世界各地均有报告,无种族差异。     

甲基泼尼松龙冲击联合环磷酰胺治疗儿童局灶节段性肾小球硬化

局灶节段性肾小球硬化(FSGS)是原发性肾病综合征(NS)的病理表现之一,糖皮质激素口服完全缓解率仅为20％,多数呈激素耐药,起病10年后 30％～40％进入肾衰竭,是儿童慢性肾衰竭的最常见原因。近几年国外有报道采用甲基泼尼松龙     

局灶性节段性肾小球硬化的研究现状

局灶性节段性肾小球硬化是儿童期肾功能衰竭的主要病因之一 ,发病机制复杂 ,目前有关研究认为肾小球脏层上皮细胞的数目及结构的改变导致蛋白尿及肾小球硬化。局灶性节段性肾小球硬化的临床治疗较为困难 ,目前无一种方案的应用可取得完全缓解 ,早期联合、多环节针对发病机制用药的综合治疗方案可取得较好的缓解率。     

局灶性节段性肾小球硬化的研究现状

局灶性节段性肾小球硬化是儿童期肾功能衰竭的主要病因之一，发病机制复杂，目前有关研究认为肾小球脏层上皮细胞的数目及结构的改变导致蛋白尿及肾小球硬化。局灶性节段性肾小球硬化的临床治疗较为困难，目前无一种方案的应用可取得完全缓解，早期联合、多环节针对发病机制用药的综合治疗方案可取得较好的缓解率。     

儿童原发性局灶节段性肾小球硬化症治疗进展

局灶节段性肾小球硬化症(FSGS)是儿童常见肾小球疾病,临床多表现为肾病综合征。糖皮质激素是FSGS的一线治疗药物,但相当一部分患儿对激素治疗反应不佳,最终进展至终末期肾病,因此各种新型FSGS治疗药物不断开发,并取得一定疗效。文章综述儿童原发性FSGS的治疗进展。     

肾病综合征分子遗传学研究进展

肾病综合征（NS）是儿科常见的肾脏疾病,尽管临床上依据“三高一低”的症状及肾活检进行诊断,但由于发病机制不清楚,使我们不易作出其对激素治疗是否敏感的准确判断。随着分子遗传学的发展确定了一些NS相关新基因,为我们做到“基因诊断”、指导治疗奠定了基础。该文主要讨论先天性NS、常染色体隐性或显性家族性局灶节段性肾小球硬化（FSGS）、散发性NS以及综合征性弥漫性系膜硬化（DMS）或FSGS的分子遗传学进展     

Focal segmental glomerulosclerosis associated with acute cytomegalovirus infection in a renal transplant

Focal segmental glomerulosclerosis (FSGS) occurring in association with cytomegalovirus (CMV) infection in a renal transplant patient with no previous history of FSGS has rarely been reported. We present a case of a 16‐year‐old renal transplant recipient who developed acute hepatitis, leukopenia, nephrotic syndrome, and progressive renal dysfunction in the setting of acute infection with CMV. The cytomegalovirus infection was successfully treated with IV ganciclovir followed by oral valganciclovir but renal function deterioration and massive proteinuria continued. Features of FSGS were found on two renal allograft biopsies. Plasmapheresis and cyclophosphamide treatment was instituted with no clear effect on disease progress.     

Genetics of idiopathic nephrotic syndrome

Nephrotic syndrome (NS) is a pathological entity characterized by massive proteinuria and has diverse etiology. Although it is one of the most common renal diseases in children, the etiological factors responsible for idiopathic NS/FSGS remain largely unknown. Previous studies had implicated a variety of factors including genetic factors, although NS is generally regarded as a sporadic disease. Familial cases of NS have however been reported periodically, and both autosomal dominant and recessive forms have been identified. Studies of familial NS /FSGS have led to the discovery of several genes that are expressed in podocytes and are associated with proteinuria. These discoveries have shifted the focus from glomerular basement membrane (GBM) to recognition of the central role of podocytes in maintaining glomerular perm selectivity and pathogenesis of NS/FSGS. Associations with various genes (NPHS1, ACTN4, NPHS2, WT-1) and linkage to several chromosomal regions (such as 19q13,11q21,11q24) have been reported in patients with familial NS/FSGS.     

家族性局灶节段性肾小球硬化3家系临床表型与相关基因连锁分析

目的 分析3个家族性局灶节段性肾小球硬化（FFSGS）家系的临床表型,并通过连锁分析方法进行已知基因的排除性定位研究。 方法 对3个家系中的所有患者进行临床检查。应用等位基因共享分析和两点连锁分析的方法，在已知的FFSGS 相关基因NPHS1、NPHS2、ACTN4、TRPC6、CD2AP和WT1基因的所在染色体区域，选取14个微卫星标记进行连锁分析研究。结果 3个FFSGS家系的遗传方式均为常染色体显性遗传，54名家系成员中有16例患者，其临床表型不同，2个家系的起病年龄相对较大，在青少年期发病，而家系A中有2个患者发病年龄偏小，最小者1岁发病，而家系中其他患者都是在25岁以后发病。3个家系中有4例因尿毒症病故，另2例尿毒症行肾移植治疗，还有2例出现肾功能不全。其中家系A的先证者14岁即出现了肌酐增高。应用D19S191、D19S220、D19S224、D1S215、D1S416、D1S466、D11S1391、D11S1986、D11S2000等微卫星标记（STR）对家系A进行NPHS1、NPHS2、ACTN4和TRPC6基因的两点连锁分析，测得各个标记位点在重组率θ= 0 时，最大的LOD 值为0.18（D11S1391）；在θ= 0.1 时，最大的LOD 值也为0.18（D11S1986）；在θ= 0.2 时，得到本组最大的LOD 值也只为0.47（D19S220），均不支持连锁。提示家系A与所检测的9个微卫星DNA 标记位点无共分离。用上述微卫星标记以及ACTN4基因内的微卫星标记D19S422、CD2AP基因所在位点的微卫星标记D6S936和D6S1566、WT1基因所在位点的微卫星标记D11S2370对家系A进行等位基因共享分析，结果该家系致病基因与ACTN4、NPHS1、NPHS2、TRPC6、CD2AP和 WT1等基因所在位点不连锁。应用D19S191、D19S220、D19S224、D19S422、D1S215、D1S416、D1S466、D11S1391、D11S1986、D11S2000、D6S936和D6S1566等微卫星标记（STR）对家系B和C进行等位基因共享分析，结果这2个家系的致病基因与ACTN4、NPHS1、NPHS2、 TRPC6和CD2AP等基因所在位点均不连锁。结论 3个中国人常染色体显性FFSGS家系，具有明显的临床异质性。已知基因NPHS1、NPHS2、ACTN4、TRPC6、CD2AP和WT1不是家系A的致病基因；NPHS1、NPHS2、ACTN4、TRPC6和CD2AP不是家系B和C的致病基因。     

Focal segmental glomerulosclerosis with and without nephrotic syndrome in children

The clinical presentation, initial laboratory and renal biopsy findings, and course of focal segmental glomerulosclerosis (FSGS) were studied retrospectively in 57 children in order to compare findings in those with and without nephrotic syndrome and to establish factors of prognostic significance. All patients had proteinuria. Eleven patients were otherwise asymptomatic, and nephrotic syndrome did not develop (group 1); 14 patients had asymptomatic proteinuria, but nephrotic syndrome subsequently developed (group 2); 32 patients had nephrotic syndrome (group 3). There were no differences between these three groups with regard to sex, age, initial renal function, incidence of hypertension and hematuria, and pathologic findings. At the latest follow-up, five group 1 patients, six in group 2, and 14 in group 3 had chronic renal failure; the incidence was similar for those with asymptomatic proteinuria and those with nephrotic syndrome. The location of the sclerosis within the glomerulus proved to have prognostic significance. All 12 patients with peripheral FSGS maintained normal renal function, whereas in 25 of the 44 with hilar FSGS chronic renal failure developed.     

Clinical features and mutational survey of NPHS2 (podocin) in Japanese children with focal segmental glomerulosclerosis who underwent renal transplantation

Abstract:  Recurrent FSGS is a major challenge in the field of nephrology. To clarify the role of NPHS2 defects in the pathogenesis of FSGS recurrence, we sequenced all eight exons of NPHS2 in 11 Japanese pediatric FSGS patients with or without post-transplant recurrence. All patients had biopsy-proven primary FSGS, had no family history of renal diseases or consanguinity, were steroid-resistant, and received living-related renal transplantation. The mean age at onset was 5.0 ± 3.1 yr and mean age at renal transplantation was 10.4 ± 4.1 yr. Mutational analysis of NPHS2 was performed using polymerase chain reaction and direct sequencing. We found a synonymous T/C polymorphism at alanine 318 (GC C to GC T ) in seven of 11 patients but no other causative NPHS2 mutations. FSGS recurred immediately after transplant in seven patients, while the remaining four patients had no recurrence for 3.2–5.8 yr. There were no differences between recurrent and non-recurrent patients in the onset age and the interval from onset to ESRD. In conclusion, we detected no causative NPHS2 mutations in Japanese pediatric FSGS patients with or without post-transplant recurrence. Further studies on the involvement of other genes are required to better understand recurrent FSGS.     

Glomerulopathy with mesangial IgM deposits: Long-term follow up of 64 children

BACKGROUND: The aim of the present study was to investigate to what extent IgM nephropathy in children with minimal change nephrotic syndrome (MCNS) and diffuse mesangial hypercellularity (DMH) evolves to focal segmental glomerulosclerosis (FSGS). METHODS: Tissues from renal biopsies were examined by light microscopy (LM), immunofluorescence (IF) and, in four cases, by electron microscopy (EM). From a total of 352 nephrotic children, 121 had renal biopsy results as steroid dependent or resistant. A diagnostic renal biopsy was also performed in 331 children with non-nephrotic proteinuria and/or hematuria. A second renal biopsy was performed in 16 children whose renal function was impaired during the follow up. The clinical course of IgM-positive children was compared with that of IgM-negative children. RESULTS: Of the 121 nephrotic children with renal biopsy, 85 were MCNS. Twenty were IF positive mainly for IgM, six of whom (30%) presented evolution to FSGS, while of the remaining 65 IF-negative children, only three (4.6%) presented evolution to FSGS. Of the total 331 children with non-nephrotic proteinuria and/or hematuria, 139 were diagnosed as IgA--IgG nephropathy, 44 had positive IF for IgM and 148 were IF negative. Of the 44 children IF positive for IgM, seven (15.9%) presented evolution to FSGS, while none of the 148 IF-negative children presented evolution to FSGS. The follow-up time for all children ranged from 1 to 14 years. CONCLUSIONS: Of IgM nephropathy patients with MCNS and DMH, a significant percentage develop impaired renal function, due to the evolution of FSGS, as revealed by repeat biopsy during long-term follow up.     

Focal segmental glomerulosclerosis in patients with complete deletion of one WT1 allele

The renal prognosis of patients with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation syndrome (WAGR) is poor. However, the renal histology and its mechanisms are not well understood. We performed renal biopsies in 3 patients with WAGR syndrome who had heavy proteinuria. The complete deletion of one WT1 allele was detected in each patient by constitutional chromosomal deletion at 11p13 using G-banding, high-resolution G-banding, and fluorescence in situ hybridization. The patients exhibited proteinuria at the ages of 6, 10, and 6 years and were diagnosed as having focal segmental glomerulosclerosis (FSGS) at the ages of 7, 16 and 19 years, respectively. They exhibited normal or mildly declined renal function at the time of biopsy. Re-examination of a nephrectomized kidney from 1 patient revealed that some glomeruli showed segmental sclerosis, although he did not have proteinuria at the time of nephrectomy. The other 2 patients did not develop Wilms' tumor and thus did not undergo nephrectomy, chemotherapy, or radiotherapy, thereby eliminating any effect of these therapies on the renal histology. In conclusion, complete deletion of one WT1 allele may induce the development of FSGS. Our findings suggest that haploinsufficiency of the WT1 could be responsible for the development of FSGS.     

Relapse of nephrotic syndrome following remission for 20 years

Relapse of the nephrotic syndrome in a patient who was in remission for 20 years is discussed. The initial renal biopsy performed 3 years after the onset of the nephrotic syndrome showed focal and segmental glomerulosclerosis (FSGS). The second renal biopsy performed 20 years later was compatible with a diagnosis of minimal change nephropathy (MCN).