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International audience; Primary focal and segmental glomerulosclerosis (FSGS) frequently recurs after transplantation and is associated with a poor prognosis. We describe here the successful kidney graft reuse in an adult recipient, 8 months after early primary FSGS recurrence resistant to all available therapeutics. Patient 1, a 23-year-old man, followed for kidney failure secondary to primary FSGS, was first transplanted in 2018 with a deceased donor graft. Unfortunately, we observed an immediate recurrence of biopsy-proven primary FSGS. After 4 lines of treatment (intravenous cyclosporine + corticosteroids, plasma exchanges, immunoadsorption, and rituximab), the patient was still highly nephrotic and kidney function was slowly deteriorating. After approval from both the patient and the health authority (Biomedicine Agency), the graft was detransplanted 8 months after transplantation and reimplanted in patient 2, a 78-year-old nonimmunized and anephric recipient (bi-nephrectomy 2 years previously for bilateral renal carcinoma). We observed immediate kidney function and progressive resolution of proteinuria (serum creatinine of 1.2 mg/dL and proteinuria of 0.1 g/d 1 year later). Biopsies performed after surgery showed persistent FSGS lesions with a decrease in overall foot-process effacement. To our knowledge, this is the first reported case showing that kidney graft transfer may still be a viable option for refractory primary FSGS several months after transplantation.

Determining the cause of focal segmental glomerulosclerosis (FSGS) has crucial implications for evaluating the risk of posttransplant recurrence. The degree of foot process effacement (FPE) on electron micrographs (EM) of native kidney biopsies can reportedly differentiate primary FSGS from secondary FSGS. However, no systematic evaluation of FPE in genetic FSGS has been performed. In this study, percentage of FPE and foot process width (FPW) in native kidney biopsies were analyzed in eight genetic FSGS patients and nine primary FSGS patients. All genetic FSGS patients showed segmental FPE up to 38% and FPW below 2000 nm, while all primary FSGS patients showed diffuse FPE above 88% and FPW above 3000 nm. We reviewed the literature which described the degree of FPE in genetic FSGS patients and identified 38 patients with a description of the degree of FPE. The degree of FPE in patients with mutations in the genes encoding proteins associated with slit diaphragm and cytoskeletal proteins was varied, while almost all patients with mutations in other FSGS genes showed segmental FPE. In conclusion, the present study suggests that the degree of FPE in native kidney biopsies may be useful for differentiating some genetic FSGS patients from primary FSGS patients.

12th Congress of the Turkish-Transplantation-Centers-Coordination-Association (TTCCA) -- OCT 18-21, 2018 -- Trabzon, TURKEY, Taner, Sevgin/0000-0003-1578-789X, WOS: 000500179300012, PubMed: 31101172, Introduction and Aim. Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease in children. We analyzed the long-term outcome of pediatric patients with FSGS undergoing renal transplantation. the objective of the study is to report the experience of a single center and determine the incidence of recurrence, rejection, graft loss, and related risk factors. Materials and Method. This retrospective cohort study was performed between 1991 and 2018. Thirty patients with a pathologic diagnosis of primary FSGS were included in the study. the patients were diagnosed with FSGS according to histologic features in biopsies. Results. Twenty-one of the donors were deceased (70%) and 9 were alive (30%). FSGS recurred in only 2 patients. Graft loss occurred in 6 patients (20%). the causes of graft loss were chronic rejection in 4 patients and acute rejection in 2. Our graft survival rate was 100% at 1 year, 91% at 5 years, 80% at 10 years, 70% at 15 years, and 42% at 20 years. Five- and 10-year graft survival rates were 83% and 83% in living donors and 94% and 79% in deceased donors, respectively. According to Kaplan-Meier analysis, there was no statistically significant difference in terms of graft survival between living and deceased donors. Conclusion. This study, with its contribution to literature in terms of long follow-up of FSGS patients from childhood to adulthood, is important. However, further studies are required., Turkish Transplantat Ctr Coordinat Assoc

Main problem Recurrence of primary focal and segmental glomerulosclerosis following kidney transplantation (rFSGS) is a frequent and severe disease. Methods We studied the time to recurrence of FSGS and its impact on the response to plasma exchange (PE) and graft survival. Results Between 1990 and 2013, 2730 kidney transplants were performed, including 52 patients with a primary diagnosis of FSGS. Of these patients with primary FSGS, 34 (67%) developed rFSGS. We retrospectively divided these patients into two groups depending on the time to recurrence: early (up to three months after transplantation, n=26) or late (more than three months after transplantation, n=8). Survival did not significantly differ between the two groups. In cases of late recurrence, PE was started later, was performed less frequently and remission was achieved after more PE sessions and longer PE treatment than for the early group (p=0.01). In early recurrence, resistance to PE at 40 days was associated with no long-term response to PE. Conclusions PE should be performed as soon as possible after rFSGS. Patients with late rFSGS need to be offered the same treatment regime as those with early rFSGS.

Biomarcadors; Algoritme de diagnosi; Glomerulosclerosi segmentària focal Biomarcadores; Algoritmo de diagnóstico; Glomeruloesclerosis segmentaria focal Biomarkers; Diagnosis algorithm; Focal segmental glomerulosclerosis Primary or idiopathic focal segmental glomerulosclerosis (FSGS) is a kidney entity that involves the podocytes, leading to heavy proteinuria and in many cases progresses to end-stage renal disease. Idiopathic FSGS has a bad prognosis, as it involves young individuals who, in a considerably high proportion (∼15%), are resistant to corticosteroids and other immunosuppressive treatments as well. Moreover, the disease recurs in 30–50% of patients after kidney transplantation, leading to graft function impairment. It is suspected that this relapsing disease is caused by a circulating factor(s) that would permeabilize the glomerular filtration barrier. However, the exact pathologic mechanism is an unsettled issue. Besides its poor outcome, a major concern of primary FSGS is the complexity to confirm the diagnosis, as it can be confused with other variants or secondary forms of FSGS and also with other glomerular diseases, such as minimal change disease. New efforts to optimize the diagnostic approach are arising to improve knowledge in well-defined primary FSGS cohorts of patients. Follow-up of properly classified primary FSGS patients will allow risk stratification for predicting the response to different treatments. In this review we will focus on the diagnostic algorithm used in idiopathic FSGS both in native kidneys and in disease recurrence after kidney transplantation. We will emphasize those potential confusing factors as well as their detection and prevention. In addition, we will also provide an overview of ongoing studies that recruit large cohorts of glomerulopathy patients (Nephrotic Syndrome Study Network and Cure Glomerulonephropathy, among others) and the experimental studies performed to find novel reliable biomarkers to detect primary FSGS. The authors are current recipients of research grants from the Fondo de Investigación Sanitaria-Feder, Instituto de Salud Carlos III (PI17/00257, PI18/01704 and PI18/01832) and REDinREN (RD16/0009/0030).

A major obstacle in kidney transplantation for primary focal segmental glomerulosclerosis (FSGS) is the risk of disease recurrence. Recurrent FSGS affects up to 60% of first kidney grafts and exceeds 80% in patients who have lost their first graft due to recurrent FSGS. Clinical and experimental evidence support the hypothesis that a circulating permeability factor is the mediator in the pathogenesis of primary and recurrent disease. Despite all efforts, the causing agent has not yet been identified. Several treatment options for the management of recurrent FSGS have been proposed. In addition to plasma exchange, B-cell depleting antibodies are effective in recurrent FSGS. This indicates, that the secretion and/or activity of the postulated circulating permeability factor(s) may be B-cell related. This review summarizes the current knowledge on permeability factor(s) possibly related to the disease and discusses strategies for the management of recurrent FSGS. These include profound B-cell depletion prior to transplantation, as well as the salvage of an allograft affected by recurrent FSGS by transfer into a second recipient.

Recent studies suggest that complement plays a role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). Moreover, co-localization of IgM and C3 deposits with FSGS lesions has frequently been reported. Here, we investigated whether glomerular complement deposition precedes the development of FSGS and whether it represents local complement activation. Renal biopsies from 40 patients with primary FSGS, 84 patients with minimal change disease, and 10 healthy individuals were stained for C4d, C1q, and mannose-binding lectin. C4d deposits were also measured in renal allograft biopsies from 34 patients with native primary FSGS, 18 of whom subsequently developed recurrent FSGS. Lastly, we measured C4d deposits in the Munich Wistar Fromter rat model of FSGS. The prevalence of C4d-positive glomeruli was significantly higher among patients with FSGS (73%) compared to patients with minimal change disease (21%) and healthy individuals (10%). Moreover, segmental sclerosis was absent in 42% of C4d-positive glomeruli. Glomerular C1q was significantly more prevalent in FSGS compared to minimal change disease or healthy individuals, while mannose-binding lectin was infrequently observed. C4d deposition was significantly more prevalent in recurrent FSGS (72%) before the development of sclerotic lesions compared to control transplant samples (27%). Finally, at the onset of albuminuria but before the development of FSGS lesions, Munich Wistar Fromter rats had a significantly higher percentage of C4d-positive glomeruli (31%) compared to control rats (4%). Thus, glomerular C4d deposition can precede the development of FSGS, suggesting that complement activation may play a pathogenic role in the development of FSGS.

Primary focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome in adults and children and often leads to end-stage kidney disease.[1][1] The aetiology may be immune mediated or due to genetic mutations affecting glomerular proteins. Primary FSGS frequently recurs following

Introduction Primary focal segmental glomerular sclerosis (p-FSGS) is commonly complicated by recurrence (r-FSGS) post-transplantation. Our objective was to describe Irish outcomes for transplantation after ESRD due to p-FSGS, specifically rates of, and treatments for, r-FSGS. Patients and Methods Irish patients with biopsy proven FSGS were identified from the Irish National Kidney Transplant database (1982-2015). Medical record review was performed to identify predictors of r-FSGS and treatments for r-FSGS. Transplant outcomes were compared to outcomes in all renal transplants performed during the same time period using registry data. Demographic and clinical predictors of r-FSGS were identified. Statistical analysis was performed using Stata (version 13, College Station, Texas). Results 38 transplant recipients had biopsy-proven p-FSGS, 16 received a second transplant. 3846 transplants formed the comparator group. r-FSGS complicated 60.5% (23/38) of first transplants. 86% (10/12) of patients with previous r-FSGS developed recurrent disease after further transplantation. Patients with p-FSGS receiving a first renal transplant had higher rate of graft failure than those with another cause of ESRD (HR 1.9, 95% CI 1.152-3.139). 16 patients received immunotherapy for r-FSGS; 12 (86%) had at least partial response but two (14%) developed significant complications. Discussion We demonstrate high rates of r-FSGS and describe modest success from with treatments for r-FSGS. This article is protected by copyright. All rights reserved.

FSGS is a molecularly heterogeneous disease, and can be classified into primary or secondary disease. Primary FSGS can be due to immune or genetic causes. To date, more than 20 genes have been implicated in FSGS. The discovery of so many FSGS genes, together with the advent of next-generation sequencing, has led to a paradigm shift in the genetic diagnosis and management of this disease. However, genetic screening in FSGS may not be so straightforward because of the difficulty in selection and prioritization of genes. It is challenging to appreciate the prevalence of mutations in the different genes based on the current literature due to heterogeneity of the studies and rarity of the disease. Clinicians need to understand the different methods of genetic screening available. These should be weighed against practical issues such as clinical urgency, financial costs, availability of expertise, and test accessibility. Clinicians should also consider the likelihood of a genetic etiology and the clinical impact of a genetic diagnosis to decide, with the patient and family, on the extent or “aggressiveness” of the genetic screening. The main impact of a genetic diagnosis in FSGS is on the use of immunosuppressive medications as well as on peri-transplant management involving the selection of live-related donors and risk of post-transplant recurrence.

FSGS can recur after kidney transplantation and is associated with poor graft outcomes. We aimed to assess the incidence of FSGS recurrence post-transplant and determine the effect of graft source on recurrence and graft survival in patients with biopsy-proven FSGS.Using the Australian and New Zealand Dialysis and Transplant Registry, we assessed incidence of FSGS, the influence of donor type on the risk of FSGS recurrence, and graft loss in recipients with ESRD caused by primary FSGS using Kaplan-Meier and logistic regression analyses.Between 1992 and 2011, 736 first kidney transplants were performed in 666 adults and 70 children (≤20 years old) with biopsy-proven primary FSGS. FSGS recurred in 76 (10.3%) patients. Younger age (P0.001), nonwhite ethnicity (P=0.02), and having a live donor (P=0.02) were independent risk factors associated with recurrence. Median graft survival was significantly better for live donor compared with deceased donor grafts (14.8 versus 12.1 years; P0.01). Disease recurrence predicted poor graft outcomes, with 52% (95% confidence interval, 40% to 63%) 5-year graft survival in the recurrence group compared with 83% (95% confidence interval, 79% to 86%) in the group without recurrent disease (P0.001).FSGS recurrence after kidney transplantation was more common in live donor kidneys. Despite this, graft survival in live donor recipients was significantly better for both children and adults with FSGS. We propose that live donor transplantation should not be avoided in patients with FSGS.

Focal segmental glomerulosclerosis (FSGS) comprises a group of clinical-pathologic syndromes characterized by heavy proteinuria and segmental obliteration of glomerular capillaries by extracellular matrix. FSGS lesions display morphologic heterogeneity with respect to their relationship to the glomerular vascular and tubular poles, the presence of capillary collapse, and endocapillary and extracapillary hypercellularity. A working proposal, commonly referred to as the Columbia Classification, distinguishes 5 mutually exclusive morphologic variants: collapsing, tip, cellular, perihilar, and not otherwise specified (NOS), which can be applied to primary and secondary forms of FSGS. Several studies have documented significant differences in baseline clinical characteristics and outcomes between morphologic variants of primary FSGS, supporting that this classification may provide useful prognostic information. The association of certain variants with particular secondary causes of FSGS suggests pathogenetic relevance.

Purpose of review We discuss recent work on the pathogenetic mechanism of focal segmental glomerulosclerosis (FSGS) and its relationship to soluble urokinase receptor (suPAR). Recent findings Primary FSGS can affect both children and adults. The disease can recur after kidney transplantation suggesting the involvement of a causative circulating factor. Recent work suggests that approximately two-thirds of FSGS patients have elevated levels of serum suPAR, which confers risk to both native and posttransplant FSGS. Summary Future studies that are geared to understand the clinical implications of high suPAR levels in native FSGS as well as in the pretransplant and posttransplant setting will allow for better patient risk stratification and more targeted treatment options.

Primary focal segmental glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome in adults. Glucocorticoids have been evaluated in the treatment of primary FSGS in numerous retrospective studies. Evidence suggesting a role for including calcineurin inhibitors (CNIs) in early therapy remains limited. The aim of this study was to systematically review the literature examining the efficacy of CNIs in the treatment of primary FSGS both as first-line therapy and as an adjunctive agent in steroid-resistant patients, with respect to remission in proteinuria and renal survival.PubMed and EMBASE were searched from inception to August 2014 for prospective controlled trials, and case-control and cohort studies.After systematically applying our inclusion criteria, a total of 152 titles and abstracts were identified. Six randomized controlled trials and 2 cohort studies were reviewed. Three randomized controlled trials compared CNIs with placebo or supportive therapy. The pooled relative "risk" of proteinuria remission associated with cyclosporine was 7.0 (95% confidence interval, 2.9-16.8) compared with placebo/supportive therapy. There was very low heterogeneity among these studies with anThe relatively small number of included studies and their heterogeneity with respect to treatment protocols, and possible publication bias, limit conclusions drawn from this systematic review.The efficacy of CNIs has been evaluated in steroid-resistant primary FSGS patients. There is no evidence supporting their role as first-line therapy. Further studies are needed to determine this role.La glomérulosclérose segmentaire et focale (FSGS) primaire est la principale cause du syndrome néphrotique chez les adultes. De nombreuses études rétrospectives ont fait état du rôle des glucocorticoïdes dans le traitement de la FSGS primaire. Toutefois, les preuves suggérant que les inhibiteurs de la calcineurine (les CNI) puissent jouer un rôle en début de traitement demeurent limitées. L’objectif de cette étude était de faire une revue systématique de la littérature discutant de l’efficacité des CNI dans le traitement de la FSGS primaire, en tant que traitement de premier recours ou à titre d’agent thérapeutique auxiliaire, chez les patients résistants aux stéroïdes, relativement à la rémission de la protéinurie et à la survie.Les bases de données de PubMed et d’EMBASE ont été consultées afin de constituer une liste des études de cohorte ou de cas-témoin, de même que des essais cliniques prospectifs contrôlés ayant été publiés sur le sujet jusqu’en août 2014.À la suite de l’application systématique des critères d’exclusion, un total de 152 titres et abrégés ont été répertoriés, dont six essais contrôlés randomisés et deux études de cohorte ont fait l’objet d’un examen. Parmi les essais contrôlés randomisés, trois comparaient les CNI à un placebo ou à un traitement de soutien. Le regroupement des valeurs de risque relatif tirées de ces trois études en regard de la rémission de la protéinurie associée à la cyclosporine a permis d’obtenir une valeur moyenne de 7,0 (intervalle de confiance à 95% entre 2,9 et 16,8) à comparer aux valeurs obtenues pour le placebo ou pour le traitement de soutien. Parallèlement, l’hétérogénéité entre ces études s’est avérée très faible (Les conclusions tirées de cette revue systématique sont limitées par de possibles biais de publication, de même que par le nombre restreint d’études retenues et l’hétérogénéité de celles-ci en regard du protocole de traitement.L’efficacité des CNI a été évaluée chez les patients atteints de FSGS primaire et réputés résistants aux traitements par les stéroïdes. Il n’existe aucune preuve évidente supportant l’usage des CNI comme traitement de premier recours. Des études supplémentaires sont nécessaires afin de mieux définir le rôle des CNI dans ce contexte.

FSGS is a lesion, not a disease. The separation into primary FSGS (a result of immunologic-mediated injury) versus secondary FSGS (related to a variety of causes) is often difficult. Even when this particular issue is carefully evaluated, the therapeutic implications are not always apparent. Newer literature on both biomarker discovery and on the genetic basis of FSGS is reviewed in this context. In addition, the thorny implications of obesity as it relates to the FSGS lesion are discussed. An overall practical algorithmic approach to the management and treatment of the FSGS lesion that integrates these controversial overlap areas is suggested.

The urokinase-type plasminogen activator receptor (uPAR) has important functions in cell migration. uPAR can be shed from the cell membrane resulting in soluble uPAR (suPAR). Further cleavage gives rise to shorter fragments with largely unknown functions. Recent studies have demonstrated that both overexpression of uPAR on podocytes and the administration of suPAR cause proteinuria in mice. The common pathogenic mechanism involves the activation of podocyte β3-integrin. Increased activation of β3-integrin is also observed in patients with focal and segmental glomerulosclerosis (FSGS). These observations form the basis for the hypothesis that suPAR may be the circulating factor causing FSGS. A recent study fosters this idea by demonstrating increased suPAR levels in the serum of patients with FSGS and reporting an association with recurrence after transplantation and response to plasmapheresis. However, this study was heavily biased, and subsequent studies have given conflicting results. Although the experimental work is very suggestive, at present there is no proof that any known human suPAR fragment causes FSGS in humans. We therefore suggest that the measurement of suPAR using currently available assays has absolutely no value at the present time in decision-making in routine clinical practice.

Background: There is no information on the frequency and clinicopathological presentation of the variants of primary focal segmental glomerulosclerosis (FSGS) in adults presenting with idiopathic nephrotic syndrome (INS) in Pakistan. Objectives: The aim of this study was to determine the frequencies of different histologic variants of primary FSGS with INS at our center and to compare our findings with those published in literature. Patients and Methods: All consecutive adults (≥18 years) with INS, and diagnosis of FSGS on renal biopsies, were included. Their clinicopathological features at the time of presentation were retrieved and compared among the variants. Results: There were 120 (65.2%) males and 64 (34.8%) females. The mean age was 30.62±12.02 years. The mean 24-hr urinary protein excretion was 4.69±2.36 grams. Microscopic hematuria was found in 30 (16.3%) patients. The mean serum creatinine was 1.58±0.87 mg/dL. At presentation, 128 (69.6%) patients were normotensive, while 56 (30.4%) exhibited hypertension. FSGS, not otherwise specified (NOS) was the predominant variant, comprising 76.6% of all; collapsing variant comprised 12%, tip variant, 9.8%, perihilar, 1.1%, and cellular, 0.5%. The mean number of glomeruli involved by segmental scarring was 3.41±2.87 and there was significant difference among the variants (p= 0.001). Arteriolopathy was found in 23.4 % cases and fibrointimal thickening of arteries in 18.5%. Tubular atrophy and interstitial fibrosis (IF/TA) was noted in 93% of cases. There was no significant difference in vasculopathy and IF/TA among the variants. Conclusions: Collapsing variant was the second most common variant following NOS and these findings are different from other regional studies.

Over the last 20 years, primary FSGS has emerged as one of the leading causes of idiopathic nephrotic syndrome in adults, particularly among African Americans. In nephrotic patients, progression to ESRD often occurs over the course of 5-10 years, whereas non-nephrotic patients and those entering a remission have an extremely favorable prognosis. As a result, it is in patients who remain persistently nephrotic despite conservative therapy that a more aggressive therapeutic approach is taken. Primary FSGS was once considered an entity nonresponsive to prednisone or immunosuppressive agents, but it has become apparent over the last 20 years that a substantial portion of nephrotic adults with primary FSGS do respond to treatment with a significantly improved prognosis. The recent histologic classification proposed for FSGS has provided additional insights into the prognosis and response to therapy. This article reviews the current knowledge regarding the presentation, prognosis, and therapeutic approach in adults with primary FSGS.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is the most frequent primary glomerulopathy in Brazil and its incidence is increasing worldwide. Pathogenesis is related to podocyte injury, which may be due to several factors including viruses, drugs, genetics and immunological factors. In 2004, the Columbia classification of FSGS identified five histological variants of the disease: collapsing (COL), usual (NOS), tip lesion (TIP), perihilar (PHI) and cellular variant (CEL). The objective of this study was to classify the FSGS biopsies in these morphological variants. METHODS: One hundred thirty-one cases of renal biopsies with primary FSGS diagnosis, which had been performed at a Brazilian reference center from 1996 to 2006, were classified according to the Columbia criteria. RESULTS: FSGS cases were distributed as follows: 38.2% NOS variant, 36.6% COL, 14.5% TIP, 6.9% PHI and 3.8% CEL. CONCLUSION: COL variant of FSGS seems to be more prevalent in Brazil in comparison with other centers worldwide, which may be related to environmental and socioeconomic factors. INTRODUÇÃO: A glomerulosclerose segmentar e focal (GESF) é a glomerulopatia primária mais frequente no Brasil e sua incidência está aumentando em todo o mundo. Sua patogênese está relacionada com a lesão de podócitos, que pode ser devida a vários fatores, incluindo vírus, drogas, fatores genéticos e imunológicos. Em 2004, a classificação de Columbia GESF definiu cinco variantes histológicas da doença: colapsante (COL), usual (NOS), lesão apical (TIP), Peri-hilar (PHI) e variante celular (CEL). O objetivo deste estudo foi classificar as biópsias com diagnóstico de GESF nessas variantes morfológicas. MÉTODOS: Cento e trinta e um casos de biópsias renais com diagnóstico de GESF primária em um centro brasileiro de referência em nefrologia, no período de 1996 a 2006, foram classificados de acordo com os critérios de Columbia. RESULTADOS: Os casos se distribuíram da seguinte forma: 38,2% da variante de NOS; 36,6% de COL; 14,5% de TIP; 6,9% de PHI; 3,8% de CEL. CONCLUSÃO: A variante COL de GESF parece ser mais prevalente no Brasil do que em outros centros internacionais e isso pode ser reflexo de fatores socioeconômicos e ambientais.

Background: The therapeutic effects of immunosup- pressive agents such as cyclosporin A, mycopheno- late mofetil, rituximab and sirolimus on primary focal segmental glomerulosclerosis (FSGS) remain contro- versial. The present study was intended to review and analyze the treatment results of immunosuppressive agents for primary FSGS in child and adult patients. Methods: Complete remission rates and partial remis- sion rates were extracted from published articles and analyzed using statistical tests. Results: Cyclosporin A was effective in the treatment of child and adult patients with idiopathic FSGS. Ritux- imab therapy displayed a higher complete remission and partial remission rate in children than in adult FSGS patients. Conclusions: Multiple-center large-scale rigorous tri- als should be considered to evaluate the risk-benefit ratio of immunosuppressive treatment in patients with primary FSGS.

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 (GCC to GCT) 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.

Minimal-change disease (MCD) and primary FSGS are important causes of idiopathic nephrotic syndrome (INS) and, in the case of FSGS, end-stage renal failure. Intriguing features of these diseases include their frequent response to steroids, their association with immune abnormalities, the existence

Experience with early corticosteroid withdrawal (CSWD) in renal transplant recipients with focal segmental glomerulosclerosis (FSGS) has not been previously reported. Since corticosteroids are used to treat primary FSGS, concern exists as to whether early CSWD regimens will be associated with an increased risk of FSGS recurrence posttransplant. The purpose of the present study was to evaluate the results of early CSWD in FSGS recipients and compare these results to a historic control group of FSGS patients who underwent renal transplantation under corticosteroid-based immunosuppression. Methods Forty-three patients with FSGS underwent renal transplantation with early CSWD. Results in these patients were compared to FSGS patients that underwent renal transplantation with chronic corticosteroid therapy. All rejection episodes were biopsy proven with grading by Banff criteria. Statistical analyses included Student's t test and chi square tests. Results Results in 43 patients with a median follow-up of 569 days were analyzed and compared to control patients. There was no significant difference in recurrent FSGS, time to recurrence, or graft loss. Conclusion CSWD does not increase risk for recurrence of FSGS. These observations indicate that ECSW can be achieved in FSGS patients, thereby affording them the benefits of steroid elimination.