The Significance of Focal Global Sclerosis in Idiopathic Nephrotic Syndrome

ABSTRACT. The clinical course of five pediatric patients with idiopathic nephrotic syndrome associated with focal global sclerosis in renal biopsy was analyzed retrospectively. The condition was defined as complete obsolescence of more than 15 % of glomeruli associated with tubular atrophy and interstitial fibrosis. At onset, all children had a steriod-sensitive relapsing nephrotic syndrome. Two became steroid-dependent and one steroid-resistent. Cyclophosphamide or chlorambucil treatment was initially followed by remission in all patients; a second course was successful in one of two patients. After 12 to 18 years of observation, four patients are in remission for periods of 2 to 12 years. Glomerular filtration rate is slightly reduced in only one patient. This study suggests that the clinical course of children with idiopathic nephrotic syndrome associated with focal global sclerosis is similar to that observed in patients with minimal glomerular changes but different from that in patients with focal segmental sclerosis.     

The significance of focal sclerotic lesions of glomeruli in children.

To establish the relationship between the type of focal sclerotic lesion of glomeruli and the development of progressive renal disease, the clinical courses of 20 children with focal segmental and 7 with focal global sclerosis were analyzed. Only five patients, all of them with focal segmental sclerosis, did not have the nephrotic syndrome, although all had proteinuria. Results suggest that patients with focal global sclerosis have a course identical to that of children with the minimal lesion form of nephrotic syndrome: onset in early childhood, response to steroid therapy, and a relapsing, nonprogressive course. Focal segmental sclerosis, in constrast, is characterized by older age at onset, high incidence of nephritic symptoms, lack of response to steroid therapy, and a progressive course with histologic and functional deterioration. Since most published reports have not distinguished between these two entities, a more favorable prognosis in focal segmental sclerosis may be inferred than is actually the case.     

Nephrotic syndrome in indian children.

A clinicopathological study of 206 Indian children with nephrotic syndrome showed a primary renal cause in 195 (96%), of which 77% were boys. In 126 children (96 boys, 30 girls) onset of the disorder occurred before the age of 5 years. Renal biopsy showed minimal lesions in 150 patients (77%); in 85 of these biopsy was done 3 months to 16 years after onset of the nephrotic syndrome. Significant renal histological abnormalities in 45 cases were labelled as mesangiocapillary 8, mesangioproliferative 4, proliferative with extensive crescents 2, membranous 3, focal segmental glomerulosclerosis 9, focal global glomerulosclerosis 2, advanced nonspecific 8, and mild proliferative 9. Nephritic manifestations were mainly associated with significant renal lesions, which were more frequently encountered when the onset of disease was after the age of 5 years. Clearance of proteinuria with corticosteroid therapy was practically confined to patients with minimal or mild renal histological changes. Our findings suggest that the pattern of idiopathic nephrotic syndrome in Indian children is similar to that reported from Western countries.     

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.     

Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance study

Aim: To describe the demographic, clinical features, steroid response, histopathology and complications of all children diagnosed with idiopathic nephrotic syndrome (INS) in New Zealand over a 3-year period. Methods: A questionnaire seeking relevant clinical information was sent to all paediatricians who reported a new case of nephrotic syndrome to the New Zealand Paediatric Surveillance Unit. A follow-up questionnaire was sent to reporting paediatricians after the first 12 months of follow-up. Results: The incidence was 1.9 children per 100,000 under age 15 years. There was no significant difference in INS between ethnic groups. Approximately 80.4% were steroid responsive with median time to response of 8.4 days and mean time to relapse was 15.1 +/- 12.1 weeks (10.1-19.8 95% confidence interval). Follow-up at 12 months after diagnosis showed that two-thirds were either steroid dependent or frequent relapsers. Steroid resistance patients had a more variable course with some developing chronic renal failure and other remaining persistently nephrotic. Conclusion: The incidence and outcome of children with INS are similar to overseas studies. A large variety of steroid treatment regimens were noted. Current evidenced-based guidelines to treat INS were used infrequently.     

环孢素A治疗儿童不同病理类型肾病综合征83例的疗效观察

目的　研究环孢素A(CyA)治疗儿童不同病理类型肾病综合征的临床疗效及意义。方法　 83例肾病综合征患儿入院后逐渐减用激素 ,给予口服CyA ,剂量 5mg/ (kg·d) ,疗程 3～ 6个月 ,并监测血浓度调整CyA的剂量。结果　 83例患儿经治疗后 ,尿蛋白转阴者 4 5例 (完全缓解率 5 4 % ) ,尿蛋白减少者 2 3例 (部分缓解率 2 8% ) ,未缓解 15例 (18% ) ;总有效率达 82 %。不同病理类型治疗反应 :微小病变型肾病有效率为 86 % ,系膜增殖性肾小球肾炎为 84 % ,膜增殖性肾小球肾炎为 3/ 5 ,局灶节段性肾小球硬化为 2 / 4。显效时间为 7～ 4 5d ,其效应多出现于用药 1个月内。服药后分别于 1周和 2周末 ,测定CyA的血药浓度 ,有效血浓度维持在 10 0～ 2 0 0 μg/L ,可使大部分患儿病情顺利缓解 ,疗程一般在 3～ 6个月。 83例患儿都进行了随访 ,其中 6 8例经CyA治疗缓解后的 17例在减量或停药后出现复发 ,复发率为 2 5 % ,复发的患儿重新服用CyA仍然有效。治疗过程中 5例患儿出现一过性尿肌酐的增加 ,8例尿N 乙酰 β D 氨基葡萄糖苷酶轻微增加 ,一般减量或停药后可逆转。 结论　CyA是替代皮质激素治疗难治性肾病的较好方法之一 ,能有效而快速达到治疗难治性肾病的目的 ,其治疗效果与有效的血药浓度和病理类型有关     

Clinical review of idiopathic versus hepatitis B surface antigen related forms of membranous glomerulonephritis.

Clinical features and therapeutical approaches in 10 cases of membranous glomerulonephritis (MGN) have been reviewed in an attempt to identify predictive indices of prognosis, and features distinguishing between idiopathic and hepatitis B surface antigen (HBsAg) related forms of glomerulopathy. Five of these children (age range 8-10 years) had HBsAg associated MGN and the other five (age range 12-16) lacking this antigen were defined as idiopathic MGN. The follow up was nine months to 10 years (mean 4.3 years). All had nephrotic syndrome during the course of their disease. There were no distinguishing clinical features nor any difference in the outcome between these two groups. None of the clinical findings including the presence of HBsAg, adversely affected outcome. All patients in the idiopathic group and three of the five in the HBsAg related group received immunosuppressive treatment. Overall complete remission was achieved in four of the five HBsAg associated patients and in three of the idiopathic patients plus partial remission in one of each group. Immunosuppressive treatment caused no complications, and beneficial results of the treatment particularly in the idiopathic MGN group were observed.     

他克莫司在儿童肾脏疾病中的临床应用及作用机制

儿童肾小球疾病的发病机制中免疫因素是主要致病因素之一。他克莫司作为继环孢菌素A之后临床应用的一种强而有效的免疫抑制剂,近年来在儿童肾脏疾病治疗中的地位与作用日渐被重视。他克莫司在针对难治性肾病综合征包括激素依赖型、激素耐药型和频繁复发型等肾小球疾病治疗中取得了良好的效果。该文从作用机制入手,综述他克莫司在肾病综合征、局灶节段性肾小球硬化、系膜增生性肾小球肾炎、膜性肾病、狼疮性肾炎等儿童肾脏疾病中的应用。     

Evaluation and management of steroid-unresponsive nephrotic syndrome

PURPOSE OF REVIEW: Idiopathic nephrotic syndrome in children is commonly associated with minimal change disease and response to steroid therapy. Steroid-unresponsive nephrotic syndrome is often characterized by persistent proteinuria and progression to chronic kidney disease. Focal segmental glomerulosclerosis is the leading cause of steroid-unresponsive nephrotic syndrome in childhood. There is no uniformed consensus as to the treatment of steroid-unresponsive nephrotic syndrome. Advances in the pathogenesis, genetics and biomarkers or surrogate markers may be useful for the diagnosis and identification of patients with steroid-unresponsive nephrotic syndrome, severity of disease, progression and response to therapy. RECENT FINDINGS: This review is intended to describe some of the recent changes in the epidemiology of steroid-unresponsive nephrotic syndrome, in particular focal segmental glomerulosclerosis, its pathogenesis and alternative therapies. SUMMARY: Recent studies in both children and adults have shown an increase in the incidence of focal segmental sclerosis as a cause of steroid-unresponsive nephrotic syndrome. Advances in the pathogenesis and noninvasive methods of diagnosis may allow for the identification of steroid-responsive patients.     

Nephrotic syndrome associated with acquired immunodeficiency syndrome in children

We report here the cases of 15 children in whom nephrotic syndrome developed, from among 164 children (55% male, 90% black) followed in our acquired immunodeficiency syndrome clinic from 1984 through 1990. Mean age at onset of nephrotic syndrome was 4.9 +/- 2.6 years. Fourteen patients were black and one was Hispanic. Seventy-three percent of our patients with nephrotic syndrome were girls. The mean duration of clinical acquired immunodeficiency syndrome before development of nephrotic syndrome was 1.7 +/- 1.1 years. In eight patients, nephrotic syndrome appeared between 3 and 11 months after intravenous infusions of immune globulin or albumin were administered as part of a research protocol; this incidence (8/47) was higher than the incidence of nephrotic syndrome among those who did not receive intravenous infusions (7/117, p less than 0.05). Tissue for histologic examination was available for 80% of the patients, and histologic examination demonstrated mesangial hypercellularity (5 patients), focal segmental glomerulosclerosis (4 patients), minimal change disease (2 patients), and IgM nephropathy (1 patient). Deposition of one or more immunoglobulins was noted in all but one patient studied with immunofluorescence. Corresponding electron-dense deposits were seen by electron microscopy in 78% of specimens. Prednisone did not induce a remission of nephrotic syndrome in the 13 patients treated, whereas cyclosporine did so in the 3 patients to whom it was administered. Five patients were in the end stage of renal disease within 8 months. Successful maintenance peritoneal dialysis was performed in three patients, but 80% of patients have died of human immunodeficiency virus-related complications; one patient was lost to follow-up. We conclude that immune-complex deposition is consistently seen in children with human immunodeficiency virus-associated nephrotic syndrome. This nephrotic syndrome is resistant to steroid therapy, but we observed a remission of the proteinuria with cyclosporine therapy in three patients. For patients with end-stage renal disease, maintenance peritoneal dialysis may improve the quality of life.     

Urinary protein electrophoresis patterns in childhood idiopathic nephrotic syndrome

We investigated the utility of a standard urinary protein electrophoresis (UPEP) to distinguish among three common variants of childhood idiopathic nephrotic syndrome (NS). The UPEP was performed on 66 urine samples obtained during a disease relapse in 43 children and adolescents with idiopathic NS. There were 15 children with minimal change disease (MCD), 11 with IgM nephropathy (IGMN) and 17 with focal segmental glomerulosclerosis (FSGS). Fourteen of the 26 children (54%) with MCD or IGMN and 16/17 (94%) of the patients with FSGS manifested a frequently relapsing or steroid dependent course. The mean percent albumin and gamma globulin excretion in the UPEP in patients with MCD and IGMN were 75.5 and 2.9 versus 72.6 and 3.9, respectively (p = NS). Both patterns were significantly different from that observed in FSGS, albumin 62.2%, gamma globulin 7.1% (p less than 0.005). Although the percent gamma globulin excretion was inversely related to GFR in children with FSGS, this measurement exceeded a 4.3% cutoff in 9 of these patients while their GFR was normal (less than or equal to 80 ml/min/1.73M2). Therefore, we recommend the use of the UPEP as a marker of urinary protein selectivity and to monitor children with high-risk nephrotic syndrome i.e., those with a frequently relapsing or steroid dependent clinical course, for histological transitions.     

The role of immunosuppressive agents in the treatment of nephrosis in children

Good clinical results are well known with the use of immunosuppressive therapy in children with idiopathic nephrotic syndrome; more recently, biological data have enhanced immunological anomalies, concerning mainly T helper lymphocytes. The need for steroids may decrease when relapsing nephrotic syndrome is associated with steroid intoxication and is absent when corticoresistance occurs. In these cases, the use of immunosuppressive agents is justified, but limited by side effects and toxicity. In patients treated with alkylating agents and now cyclosporine, good responses are often seen in frequently relapsing children whereas the course of steroid-resistant nephrotic syndrome is not significantly modified. However, the definite appreciation of such therapeutic results has to be further precised by both histological data and multicentric studies concerning new protocols.     

Genetics of the nephrotic syndrome

There are a large number of glomerular diseases that may be responsible for a nephrotic syndrome, the most frequent in childhood being minimal change disease. In the past few years, the molecular genetic basis of several conditions that may cause a nephrotic syndrome have been identified. Denys-Drash syndrome and Frasier syndrome are related diseases caused by mutations in the WT1 gene. Familial forms of idiopathic nephrotic syndrome with focal and segmental glomerular sclerosis/hyalinosis have been identified with an autosomal dominant or recessive mode of inheritance and linkage analysis have allowed to localize several genes on chromosomes 1, 11 and 17. The gene responsible for the Finnish type congenital nephrotic syndrome has been identified. This gene, named NPHS1, codes for nephrin, which is located at the slit diaphragm of the glomerular podocytes and is thought to play an essential role in the normal glomerular filtration barrier.     

Preparing for a kidney transplant: Medical nephrectomy in children with nephrotic syndrome

Nephrotic syndrome is characterized by proteinuria, hypoalbuminemia, and general edema. These symptoms may persist in children who reach ESRD, which is unfavorable for the patient's allograft outcome. In addition, this may hamper early diagnosis of a relapse after transplantation. Surgical bilateral nephrectomy is often considered for that reason, but medical nephrectomy may be a less invasive alternative. In this retrospective single‐center case series, we identified all children on dialysis with ESRD due to nephrotic syndrome in which a medical nephrectomy was attempted before kidney transplantation between 2013 and 2018. Outcome was measured by urine output and serum albumin levels. Eight patients with either congenital nephrotic syndrome or focal segmental glomerular sclerosis were included in the study. All patients received an ACE inhibitor as drug of first choice for medical nephrectomy, to which 5 patients responded with oligoanuria and a significant rise in serum albumin, and 3 patients responded insufficiently. In 1 of these 3 patients, diclofenac was added to the ACE inhibitor, with good result. In the other 2 patients, indomethacin was initiated without success, and surgical bilateral nephrectomy was performed. Overall, 6/8 patients had a successful medical nephrectomy and did not need surgical nephrectomy. No recurrence of nephrotic syndrome was found after kidney transplantation in all but one. Medical nephrectomy with ACE inhibitors and/or non‐steroidal anti‐inflammatory drugs is a safe and non‐invasive therapy to minimize proteinuria in children with ESRD due to nephrotic syndrome before kidney transplantation. We suggest that this strategy should be considered as therapy before proceeding with surgical nephrectomy.     

Primary nephrotic syndrome during childhood in Turkey

BACKGROUND: Minimal change nephrotic syndrome (MCNS) is the most common cause of primary nephrotic syndrome (NS) during childhood. However, recent studies from different countries have reported an increasing incidence of focal segmental glomerulosclerosis (FSGS) in children. METHODS: This is a retrospective study in which 392 Turkish children who were diagnosed with NS during the last 10 years and were followed for at least 2 years, were evaluated. Mean age of the study group was 4.6 +/- 3.4 years (range 0.9-16 years) and 232 were male and 160 were female. RESULTS: In total, 280 patients were diagnosed as MCNS with their initial presentations, laboratory features, and clinical course. Kidney biopsy was performed in the remaining 112 children according to current recommendations. The results showed that membranoproliferative glomerulonephritis (MPGN) was the most common histopathologic diagnosis, 38 (34%) of the 112 patients were found to have MPGN. The number diagnosed as FSGS was 26 (23%). A significant difference was found between the age groups for both MPGN and FSGS, the former being more common in children >6 years of age and the latter more frequent in children 相似文献   

TRPC6基因变异致儿童激素耐药型肾病综合征四例并文献复习

目的:探讨TRPC6基因变异致儿童激素耐药型肾病综合征(SRNS)的特征、治疗及预后。方法:回顾性分析2017年1月至2019年12月在上海市儿童医院肾脏风湿科住院的4例(SRNS)且经基因检测为TRPC6变异患儿的临床资料。以“肾病综合征”“TRPC6”“儿童”“nephrotic syndrome”“TRPC6 variation”“child”为检索词,检索建库至2020年8月中国知网数据库、万方数据库、维普数据库及PubMed数据库并进行文献复习。结果:4例SRNS患儿中,男1例、女3例,起病年龄4岁1月龄至12岁2月龄。临床均以浮肿、大量蛋白尿、低蛋白血症起病,4例出现贫血,2例出现继发性甲状旁腺功能亢进,1例肾萎缩。肾脏病理结果示1例为免疫复合物相关性肾炎,3例为局灶节段肾小球硬化。4例患儿病初予足量糖皮质激素治疗4周以上,均为激素耐药,后予糖皮质激素联合免疫抑制剂(如环磷酰胺、钙调神经磷酸酶抑制剂、霉酚酸酯)治疗,症状没有改善。4例患儿2~6个月进展为终末期肾病。全外显子测序显示4例患儿TRPC6基因变异类型分别为c.2684G>T、c.523C>T、c.2678G>A、c.2683C>T,均为新发变异。文献检索纳入中文文献1篇,外文文献9篇,共27例。汇总分析31例(包括本组)病例资料,其中18例错义变异,移码变异、同义变异、剪切变异各1例。起病年龄4月龄至14岁,18例患儿临床表现为大量蛋白尿、低蛋白血症,6例仅表现为蛋白尿,19例患儿病理类型为局灶节段肾小球硬化,IgA肾病、微小病变各2例,塌陷性肾小球病、C1q肾病、免疫复合物相关性肾小球肾炎各1例。18例患儿激素治疗无效,11例钙调神经磷酸酶抑制剂类药物无效。该疾病预后不佳,12例患儿出现肾衰竭,进展至终末期肾病时间为4个月至13.8年。结论:TRPC6基因变异致SRNS的患儿起病年龄较小,病理特征多为局灶节段肾小球硬化,激素及免疫抑制剂治疗多无效,进展迅速预后差。     

Nephrotisches Syndrom im Kindesalter

Nephrotic syndrome is defined by severe proteinuria and hypoalbuminemia and is one of the most common renal diseases in the pediatric population. Nephrotic syndrome in children is classified by the criteria etiology, age at onset, response to glucocorticoids and histomorphology. Due to its etiology the common primary nephrotic syndrome has to be distinguished from secondary forms within the scope of other underlying diseases. The rare congenital forms have mostly a genetic background. Response to steroid therapy is highly relevant in terms of clinical course and prognosis. Primary steroid resistance affects about 10% of patients with idiopathic nephrotic syndrome. In these patients focal-segmental glomerulosclerosis is the leading histological finding, whereas in steroid-sensitive nephrotic syndrome minimal change glomerulonephritis is mostly found. In cases of frequent relapse or steroid dependency alternative immunosuppressive treatment options with e.g. cytostatic drugs, calcineurin inhibitors or mycophenolic acid should be considered to avoid steroid-associated side effects.     

Focal glomerulosclerosis in renal allografts: association with the nephrotic syndrome and chronic rejection.

Focal segmental and/or global sclerotic glomerular lesions with hyalinosis were noted in three allografts in association with the nephrotic syndrome (NS) and chronic rejection (CR). Similar lesions were absent in eight allografts with CR without NS. Previous reports have stressed the presence of this lesion in allografts with recurrence of the disease entity "idiopathic nephrotic syndrome with focal glomerulosclerosis". Both clinical and pathologic evidence suggest that recurrence was not a factor in the pathogenesis of the lesion in the three allografts with CR and NS. The presence of these lesions in failing allografts may represent the result of CR with associated NS rather than recurrence of the disease entity.     

Clinicopathologic correlations in the nephrotic syndrome.

The wide utilization of renal biopsy and the introduction of electron microscopic and immunohistologic methods has allowed better definition of the clinico-pathological conditions associated with the nephrotic syndrome (NS). Two major categories of facts can be differentiated. In the first one, diffuse lesions of glomeruli, either secondary to specific diseases, or apparently primary diseases such as membranous or membrano-proliferative glomerulonephropathy (GN) are responsible for the increased permeability of the glomerular capillaries. In most of these, there is evidence that immunological mechanisms play a role in the injury of the glomerular capillary. Any of the following clinical symptoms are suggestive of this category of NS: an acute nephritic onset, a moderate NS, macroscopic hematuria, marked hypertension and/or renal insufficiency, poorly selective proteinuria and decreased plasma C3 levels. Patients affected with any of these glomerulopathies usually do not respond to steroids. In the second one, usually referred to as the idiopathic nephrotic syndrome (INS) the mechanism of glomerular capillary alteration is unknown and the nephrotic syndrome is more marked. Minimal change NS (MCNS) accounts for the great majority of INS and is characterized in most cases by a selective proteinuria, the absence of hematuria, a good response to steroids and a good prognosis. However, in some instances, renal biopsy reveals either diffuse mesangial proliferation (DMP) or focal glomerular sclerosis (which may be superimposed on MCNS or on DMP). In both instances, hematuria may be present and 50--75% of patients do not respond to steroids and have a poor prognosis. There is still considerable controversy about the exact relationship between these 3 patterns. We believe that they are not distinct entities but represent variants of the same disease. In addition to these 2 major categories of NS, there are, in infancy, 2 conditions associated with a NS of poor prognosis: congenital NS of Finnish type and infantile mesangial sclerosis. Since steroid-sensitive nephrosis is by far the commonest cause of NS especially in young children up to 8 years, a renal biopsy should be performed only in 2 instances: (a) when the clinical symptoms suggest diffuse glomerular lesions, and (b) when steroid resistance has been demonstrated.     

儿童IgA肾病72例临床与病理分析

目的探讨儿童IgA肾病(IgAN)的临床、病理特点及其相关关系。方法对本院2005年5月-2011年8月经肾穿刺活检确诊为IgAN的72例患儿的临床表现、临床分型、病理特点及免疫分型进行回顾性总结,并分析它们之间的相关关系。结果本组72例。男48例,女24例;年龄1岁5个月～17岁[(8.99±2.94)岁];入院时病程2 d～9 a(平均12.86个月)。临床以血尿起病者58例(包括38例肉眼血尿及5例伴水肿者),以单纯水肿起病者12例,以蛋白尿起病者2例。临床分型为肾病综合征型28例(38.89%)、孤立性血尿型19例(26.39%)、血尿和蛋白尿型13例(18.05%)、急性肾炎型10例(13.89%)、孤立性蛋白尿型2例(2.78%)。病理改变:系膜增生型肾小球肾炎40例,局灶增生型肾炎25例、毛细血管内增生型肾炎6例、新月体型肾炎1例。其中伴新月体形成者17例(占23.61%)。免疫组织化学可见多种免疫球蛋白沉积。沉积类型为满堂亮型1例、IgA+IgG+C32例、IgA型8例、IgA+IgM+IgG+C3型17例、IgA+IgM+C3型44例。结论 IgAN的临床表现形式多样,其病情轻重与起病形式无关。病理表现以系膜增生型肾小球肾炎为主,免疫球蛋白沉积以复合型为主。临床表现为肾病综合征型及血尿和蛋白尿型者病理较重,应尽早行肾穿,及时治疗。