家族性局灶节段性肾小球硬化

局灶节段性肾小球硬化(focal segmental glomerulosclerosis,FSGS)是一种肾脏病理改变,以蛋白尿、肾病综合征和进行性肾功能损害为特征,是终末期肾病的常见原因.近年来,常染色体显性遗传和隐性遗传家族性局灶节段性肾小球硬化(familial FSGS)陆续报道,家族性FSGS基因的发现将有助于了解原发性FSGS的发病机制、分子基础和病理生理.文章总结了近年来有关疾病的临床特征、诊断、发病机制、治疗及预后的研究进展.     

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。     

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。     

蛋白尿对小儿肾脏病慢性进展的影响及治疗

蛋白尿是肾脏疾病最常见的病理生理改变，其不仅是肾小球滤过屏障受损的重要标志，且作为一个独立因素参与肾脏病变过程。持续性蛋白尿会造成慢性肾病（CKD）的进展，且蛋白尿水平与慢性肾衰竭进展速度密切相关。临床观察发现，局灶节段性肾小球硬化症（RSGS）患者蛋白尿程度与预后相关，表现为非肾病型蛋白尿的FSGS患者临床经过多数较好，10年肾脏存活率在80％以上，     

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。     

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。     

紫癜性肾炎的诊断与治疗(草案)

诊断　　一、诊断标准　　在过敏性紫癜病程中 (多数在 6个月内 ) ,出现血尿和(或 )蛋白尿。二、临床分型1.孤立性血尿或孤立性蛋白尿。2 .血尿和蛋白尿。3 .急性肾炎型。4.肾病综合征型。5 .急进性肾炎型。6.慢性肾炎型。　　三、病理分级1.Ⅰ级 :肾小球轻微异常。2 .Ⅱ级 :单纯系膜增生。分为 :a.局灶 节段 ;b .弥漫性。3 .Ⅲ级 :系膜增生 ,伴有 <5 0 %肾小球新月体形成 节段性病变 (硬化、粘连、血栓、坏死 ) ,其系膜增生可为 :a .局灶 节段 ;b .弥漫性。4.Ⅳ级 :病变同Ⅲ级 ,5 0 %～ 75 %的肾小球伴有上述病变。分为 :a .局灶 节段 ;b…     

原发性局灶节段性肾小球硬化48例临床病理分析

目的 探讨原发性局灶节段性肾小球硬化（FSGS）的临床表现、肾脏病理和治疗反应的特点及关系。方法 对肾活检确诊的原发性FSGS患儿48例。男34例，女14例；年龄1．75～16．0岁。回顾性分析其临床表现、实验室指标和肾组织形态学特点，比较不同病理分型与临床的关系。结果 原发性FSGS临床诊断以肾病综合征（Ns）最多[32例（66．7％）]，肾组织病理学分型以非特殊性（NOS）FSGS最多[29例（60．42％）]，无塌陷型。各型节段硬化肾小球比例相似，球形硬化肾小球比例门部型（18．08±26．40）明显高于非特殊性FSGs（2．51±6．68）和其他2型[合计（1．81±4．06）]，差异有统计学意义（P〈0．05）；各型均有小管间质损害，血管病变均少见。结论 FSGS中高血压和肾功能不全少见，临床表现为单纯性血尿者也可发生FSGS；不同病理类型均有肾小管间质损害，但血管病变少见；激素初治大多敏感，但后期多表现为频繁复发，加用免疫抑制剂有助于提高缓解率。     

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     

Medullary nephrocalcinosis in Schimke immuno‐osseous dysplasia

Schimke immuno‐osseous dysplasia (SIOD) is a rare hereditary disease characterized by skeletal dysplasia, immune deficiency and progressive renal disease. Kidney involvement mainly determines the prognosis. The most common renal pathology is focal segmental glomerulosclerosis (FSGS). Medullary nephrocalcinosis refers to the diffuse deposition of calcium salts in renal medulla and has not previously been identified in SIOD. Here we report the first case of a pediatric patient having typical features of SIOD with medullary nephrocalcinosis.     

儿童原发性局灶节段性肾小球硬化212例临床病理分析

目的 探讨小儿原发性局灶节段性肾小球硬化(FSGS)的临床表现、肾脏病理和治疗的疗效特点,以减少或延缓终末期肾病(ESRD).方法 对近10年病理确诊的原发性FSGS患儿212例进行了回顾性分析,依据2004年D'Agati原发FSGS组织病理学新分型标准,将患儿分为非特异型、门部型、细胞型、顶部型、塌陷型共5个亚型,比较不同病理分型与其临床表现、实验室指标及治疗的疗效、分析评估病理类型与预后的关系.结果 原发FSGS临床诊断以肾病综合征最多178例(83.9%)[其中单纯型97例(45.8%),肾炎型81例(38.2%)];肾病水平蛋白尿14例(6.6%);蛋白尿或伴镜下血尿20例(9.4%).肾组织病理学分型以非特异型最多86例(40.6%),门部型25例(11.8%),细胞型58例(27.4%),顶部型31例(14.6%),塌陷型12例(5.6%).其临床病理的相关性表明,顶部型多呈单纯型肾病,塌陷型多呈肾炎型肾病,此两种亚型之间差异有统计学意义(P＜0.05),细胞型多为小婴儿,临床类型介于两者之间.本组患儿对激素的反应较差,顶部型及非特异型激素初治可敏感,但后多为频复发、依赖或转为耐药的病例;塌陷型、门部型和细胞型多为原发耐药的病例;顶部型与塌陷型两者差异有统计学意义(P＜0.05).激素联合免疫抑制剂治疗,50%以上获得完全缓解.塌陷型2年肾存活率为67%,3年肾存活率为41%.结论 原发FSGS病理分5种亚型,临床主要表现为不同程度的蛋白尿、部分伴有血尿和肾功能不全;顶部型治疗反应较好,塌陷型治疗反应及预后较差.     

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).     

Nephropathy associated with Charcot-Marie-Tooth disease

In this report, we describe a case of 14-year-old girl with Charcot-Marie-Tooth (CMT) disease and the nephropathy which was characterized by heavy proteinuria and microscopic hematuria. She progressed to renal failure with clinical duration of 4 years from the onset of disease. Renal biopsy specimens revealed the features of focal segmental glomerulosclerosis (FSGS). The patient has also a bilateral sensorineural deafness. Although the clinical features show similarities to those of the Alport syndrome, electron microscopic examination did not disclose the glomerular basement membrane changes which were characteristic of the Alport syndrome. The association of nephropathy with CMT disease is discussed, as compared with previous report.     

Focal Segmental Glomerulosclerosis Associated with Mitochondrial Cytopathy: Report of Two Cases with Special Emphasis on Podocytes

We report two children with focal segmental glomerulosclerosis (FSGS) associated with mitochondrial cytopathy (MC). Case 1 was diagnosed as MC with the findings of ptosis, ophthalmoplegia, failure to thrive, high serum lactate and pyruvate levels, ragged red fibers in muscle biopsy and the common 4.9 kb deletion in mtDNA when she was four years old. She subsequently developed FSGS four years later. Case 2 was a four month-old girl presenting with feeding difficulty from birth, with vomiting, seizures and nystagmoid eye movements, nephrotic proteinuria and hematuria. Renal biopsy revealed FSGS. Ultrastructural study demonstrated markedly pleomorphic mitochondria in podocytes with a severe effacement of foot processes. The analyses of muscle biopsy and skin fibroblasts for respiratory chain enzymes were found to be normal, while mitochondrial DNA analysis revealed the population of a single deleted mtDNA in the heteroplasmic state. The present cases illustrate FSGS as a rare renal complication of mitochondrial disease and provide further evidence of podocytes possessing abnormal mitochondria which may cause glomerular epithelial cell damage leading to glomerulosclerosis.     

Recurrence of focal segmental glomerulosclerosis in renal allograft: An in‐depth review

Vinai M, Waber P, Seikaly MG. Recurrence of focal segmental glomerulosclerosis in renal allograft: An in‐depth review.
Pediatr Transplantation 2010: 14: 314–325. © 2010 John Wiley & Sons A/S. Abstract: Focal segmental glomerulosclerosis is a major cause of chronic kidney disease requiring transplantation in children. Recurrence rate in the renal allograft transplantation is as high as 50%. Recurrence of FSGS is associated with renal dysfunction and early graft loss. To date, there is no established therapy for recurrent FSGS after renal transplant. We have reviewed the current English literature in order to summarize current practices with emphasis on graft outcome. We conclude that despite multiple approaches to the post transplant management of recurrent FSGS, none have been shown to be consistently beneficial. Currently, pheresis combined with high dose anti‐calcineurin with or without rituximab seems to be the most promising. Further controlled studies are needed to define the optimal therapeutic regimens to treat recurrent of FSGS.     

Desmin蛋白与局灶节段性肾小球硬化的相关性研究

目的 探讨局灶节段性肾小球硬化(FSGS)大鼠Desmin蛋白与足细胞损伤在FSGS发生发展中的作用.方法 测定阿霉素诱导的FSGS大鼠24 h尿蛋白定量(24 h UP)、血生化指标,计算内生肌酐清除率(Ccr);观察组织学变化并计算肾小球硬化指数(SI)、肾小球细胞外基质面积与肾小球面积之比(ECM/GA);免疫组织化学方法检测肾小球Desmin蛋白的表达,用图像分析软件测定肾小球Desmin蛋白表达的平均光密度值,并将FSGS大鼠肾小球Desmin蛋白的表达与以上指标进行相关性分析.结果 FSGS组大鼠的24 h UP、胆固醇、SI及ECM/GA明显高于正常对照组(P<0.001),白蛋白、Ccr较正常对照组明显降低(P<0.001);FSGS组大鼠Desmin蛋白的表达上调.Desmin蛋白的表达变化与24 h UP、SI及ECM/GA呈正相关(r=0.899～0.930,P均<0.05),与Ccr呈负相关(r=0.927,P<0.01),与白蛋白、胆固醇无相关性(r=0.371、0.710,P均>0.05).结论 大量蛋白尿及内生肌酐清除率下降可以作为肾小球足细胞损伤的重要特征,足细胞数量是决定FSGS的主要因素之一.     

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.