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Focal segmental glomerulosclerosis (FSGS) is a major cause of pediatric kidney failure. Most cases of FSGS in children are idiopathic and have a high risk of post-transplantation recurrence and graft loss. Common treatments for recurrent FSGS (rFSGS) post-transplantation include plasmapheresis, immunoadsorption, and/or immunomodulatory therapy. This study retrospectively evaluated the efficacy and safety of early plasmapheresis followed by rituximab for inducing and maintaining remission in rFSGS. Between 2014 and 2023, 8 of 65 pediatric kidney transplant recipients at our center were diagnosed with idiopathic FSGS. rFSGS was diagnosed based on nephrotic range proteinuria with no other cause and managed with plasmapheresis. Rituximab therapy was used for those who did not achieve complete remission with prolonged plasmapheresis or remained plasmapheresis dependent. 6 of 8 (75%) transplant recipients with idiopathic FSGS experienced rFSGS. All patients achieved partial or complete remission with plasmapheresis, with response times ranging from 8 to 379 days (median 13 days). Rituximab therapy was introduced for 5 plasmapheresis-dependent patients, leading to sustained remission and cessation of plasmapheresis in 3 patients, while 2 showed improved proteinuria and reduced plasmapheresis frequency. Adverse effects included rituximab-induced serum sickness in one patient and one mild allergic reaction. One patient experienced graft loss due to humoral rejection, but no grafts were lost to rFSGS, and all other grafts remained functional over an average follow-up of 50 months. Early plasmapheresis followed by rituximab therapy effectively induces remission in most post-transplantation rFSGS cases, is well tolerated, and prevents graft loss. Larger studies are needed to confirm these findings., (© 2024. The Author(s).)

Patients with nephrotic syndrome (NS) present with edema, proteinuria, hypoalbuminemia, and hyperlipidemia. In children, the most common causes are idiopathic minimal change disease and focal segmental glomerulosclerosis (FSGS). In adults, FSGS and membranous nephropathy (MN) are the most common primary causes. There are numerous secondary causes, including diabetes, amyloidosis, systemic lupus erythematosus, hematologic malignancies, and infections. In addition to confirming the diagnosis of NS by measuring proteinuria and serum albumin and lipid levels, evaluation should assess for secondary causes. In children, most cases are due to minimal change disease, which is responsive to steroid treatment. A glucocorticoid should be prescribed for children younger than 12 years. If the patient improves with steroid treatment, no biopsy is needed. If the patient does not improve, genetic testing and kidney biopsy are warranted to determine the diagnosis. In adults, biopsy typically is indicated for diagnosis, except in patients with positive test results for serum anti-phospholipase A2 receptor antibodies. This is diagnostic of MN. For patients with NS, management of initial and infrequent recurrences involves reduction of proteinuria with glucocorticoids. Frequent recurrences and/or the inability to discontinue glucocorticoids requires alternative therapies. Steroid-resistant NS also requires use of alternative therapies. Long-term NS management includes dietary sodium restriction, edema management, and blood pressure control. Thromboembolism prophylaxis should be considered for patients with NS and high risk of thromboembolism, particularly those with MN., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

Background: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. Patients who do not achieve remission (nonresponders) have an especially poor graft survival. However, the characteristics that may affect graft survival in nonresponders are unknown. This study aimed to determine the clinical characteristics associated with graft survival in nonresponders., Methods: We retrospectively collected the clinical records of patients with FSGS and an age at onset <16 years who experienced posttransplant recurrence of FSGS at six hospitals in Japan from 1993 to 2018., Results: Eight nonresponders with recurrent FSGS were enrolled in this study. The median time to recurrence after kidney transplantation was 1 day (interquartile range, 1-2 days). All patients received therapeutic plasma exchange and methylprednisolone pulse therapy. Rituximab was used as an add-on therapy in three patients. Five patients lost their graft within 2 years after kidney transplantation (rapid group). In contrast, three patients had much longer graft survival (nonrapid group). We compared the clinical characteristics of the rapid and nonrapid groups. Proteinuria tended to be lower in the nonrapid group at the third and subsequent months of therapy. The rapid group had persistent nephrotic syndrome. The rate of reduction in proteinuria was lower in the rapid group than in the nonrapid group., Conclusions: Our study suggests that persistent nephrotic syndrome and a low rate of reduction in proteinuria may predict rapid progression to graft failure in nonresponders., (© 2024 Wiley Periodicals LLC.)

Primary glomerulonephritis comprises several renal-limited diseases that can cause haematoproteinuria, chronic kidney disease, nephrosis and end stage kidney disease. The most common of these are IgA nephropathy (IgAN), primary membranous nephropathy (PMN), Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD). Although rare, these diseases cause a significant burden to health care systems, given the high cost of treating End Stage Kidney Disease (ESKD) with dialysis or transplantation. Until recently, the pathogenesis of primary gloerulonephritis has remained obscure. However, recent advances in understanding of how these diseases evolve has led to the introduction of novel therapeutic agents. Trials are underway or have recently completed that have huge implications for the standard of care for the primary glomerulonephritidies, and should dramatically reduce the number of patients who progress onto end stage kidney disease. This article reviews the international Kidney Disease Improving Global Outcomes (KDIGO) guidelines for the treatment of IgAN, PMN, FSGS and MCD, as well as recent research on pathogenesis and treatment.

Focal segmental glomerular sclerosis (FSGS) is a histological lesion characterized by sclerosis in sections (segmental) of some glomeruli (focal) in association with podocyte injury. Historically, FSGS has often been characterized as a disease, but it is a heterogeneous entity based on etiology, clinical course, and therapeutic approach. A unifying feature is podocyte injury and loss, which can be primary or the result of secondary maladaptive responses to glomerular stressors. FSGS has been demonstrated over time to carry a large health burden and remains a leading glomerular cause of ESRD globally. Recent clinical practice guidelines highlight the unmet scientific need for better understanding of disease pathogenesis, particularly for immunologic etiologies, as well as more targeted therapeutic drug development. In this review, we will discuss the current FSGS classification scheme, pathophysiologic mechanisms of injury, and treatment guidelines, along with emerging and investigational therapeutics., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Low-density lipoprotein apheresis (LDL-A) therapy has shown reasonable efficacy in treating nephrotic syndrome (NS) refractory to initial drug therapy and has been covered by National Health Insurance for the indication of drug-resistant focal segmental glomerulosclerosis (FSGS) since 1992 in Japan and has contributed to liberating substantial number of patients of this disease from entering into end-stage renal disease by easier practical application in actual clinical settings. Subsequently, various beneficial evidence of this treatment has accumulated on those other than FSGS, however, due to the limitation of covered disease insurance only for FSGS, patients with diseases other than FSGS are unlikely to benefit from this treatment in practice. This review summarizes the therapeutic evidence of the beneficial effect of LDL-A accumulated to date and the mechanisms of action analyzed from multifaceted perspectives. examines the applicability of expanding insurance coverage for diseases other than FSGS., (© 2023 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

Purpose: This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis (LDL-A), and lymphocytapheresis (LCAP) for adult native kidney patients with primary focal segmental glomerulosclerosis (FSGS)., Methods: A literature search was conducted using MEDLINE, EMBASE and Cochrane Databases through August 2022. Studies that reported outcomes of EPT in adult native kidneys with primary FSGS were enrolled., Results: 18 studies with 104 therapy-resistant or refractory primary native FSGS patients were identified. Overall EPT response rate was 56%, with long-term benefit of 46%. Of the 101 non-hemodialysis (HD) patients, 54% achieved remission, with 30% complete remission (CR) and 23% partial remission (PR). Of 31 patients with PE, response rate was 65%; CR and PR rates were 27% and 37% in 30 non-HD patients. Of 61 patients with LDL-A, the response rate was 54%; CR and PR rates were 41% and 3% in 29 non-HD patients. Of 10 patients with IA, response rate was 40%. Of 2 patients with LCAP, 1 achieved CR, and one developed renal failure. All 3 HD patients showed increase in urine output and gradual decrease in urine protein excretion following PE ( n  = 1) or LDL-A ( n  = 2). 2 of 3 HD patients ultimately discontinued dialysis., Conclusion: EPT with immunosuppressive therapy showed benefit in some patients with refractory primary FSGS, and PE appeared to have a higher response rate.

Focal segmental glomerulosclerosis (FSGS) is not a disease, rather a pattern of histological injury occurring from a variety of causes. The exact pathogenesis has yet to be fully elucidated but is likely varied based on the type of injury and the primary target of that injury. However, the approach to treatment is often based on the degree of podocyte foot process effacement and clinical presentation without sufficient attention paid to etiology. In this regard, there are many monogenic causes of FSGS with variable presentation from nephrotic syndrome with histological features of primary podocytopathy to more modest degrees of proteinuria with limited evidence of podocyte foot process injury. It is likely that genetic causes are largely underdiagnosed, as the role and the timing of genetic testing in FSGS is not established and genetic counseling, testing options, and interpretation of genotype in the context of phenotype may be outside the scope of practice for both nephrologists and geneticists. Yet most clinicians believe that a genetic diagnosis can lead to targeted therapy, limit the use of high-dose corticosteroids as a therapeutic trial, and allow the prediction of the natural history and risk for recurrence in the transplanted kidney. In this manuscript, we emphasize that genetic FSGS is not monolithic in its presentation, opine on the importance of genetic testing and provide an algorithmic approach to deployment of genetic testing in a timely fashion when faced with a patient with FSGS., (© 2022 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Primary focal segmental glomerulosclerosis (FSGS) treatment is based on immunosuppressive therapies. Since refractory disease is common, alternative methods are emerging. One of these methods is plasmapheresis with intravenous cyclosporine and corticosteroids, and it could be an option in post-transplant recurrent FSGS. We retrospectively investigated the efficacy of this combined treatment in adult patients with refractory primary FSGS., Methods: Seven refractory primary FSGS patients were included. Demographics, estimated glomerular filtration rates, serum albumin levels, urine protein/creatinine ratios, and previous treatments were evaluated. Also, complications and remission rates were assessed., Results: Median patient age was 23 years. Median duration of diagnosis was 2 years. Median number of plasmapheresis sessions was 14. Five of seven patients (71.4%, one complete, four partial remissions) were responders after the protocol. Changes in serum albumin levels and proteinuria after protocol were statistically significant (P = 0.018 and P = 0.018, respectively). eGFR levels did not change statistically (P = 0.753). Median follow-up duration after the treatment was 17 months. However, two patients experienced disease relapse (28.5%). End-stage kidney disease was developed in two patients. Sustained remission rate was 42.8% during follow-up (One complete and two partial remissions). Also, 42.8% of patients experienced catheter infections. Catheter-associated thrombosis that required surgery was observed in a patient., Conclusions: Plasmapheresis combined with intravenous cyclosporine and corticosteroids could be an option in refractory primary FSGS. High response rates after this protocol were encouraging. However, the relapsing disease was observed after the cessation of apheresis. Also, complications of the protocol could limit the applicability., (© 2022 Wiley Periodicals LLC.)

A 39-year-old woman was hospitalized for nephrotic syndrome. Laboratory test results showed increased serum creatinine levels and urinary excretions of beta-2-microglobulin, and N-acetyl-beta-D-glucosaminidase. A renal biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) and acute interstitial nephritis. Despite treatment with pulse steroid followed by oral high-dose glucocorticoids and cyclosporines, heavy proteinuria persisted. After low-density lipoprotein apheresis (LDL-A) therapy was initiated, her proteinuria gradually decreased, leading to complete remission. A repeat renal biopsy after treatment revealed no collapsing glomeruli. Immediate LDL-A should be performed to treat cases of collapsing FSGS poorly responding to other treatments.

Background: Up to 60% of pediatric renal transplant recipients with end-stage renal disease due to primary focal and segmental glomerulosclerosis (FSGS) may develop recurrent disease. Such recurrence is associated with poor prognosis if no remission is achieved. We report a single center experience with a protocol based on plasmapheresis and increased immunosuppression that resulted in a high long-lived remission rate., Methods: This retrospective cohort study included consecutive pediatric renal transplant patients with recurrent FSGS treated with a standardized protocol using plasmapheresis and cyclophosphamide to supplement usual post-transplant immunosuppression with calcineurin inhibitors and steroids. Relapse was defined as urinary protein/creatinine ratio > 1.0 g/g and remission as < 0.5 g/g., Results: Seventeen patients with FSGS recurrence post-transplant were treated. All had therapy resistant FSGS in native kidneys and had been on dialysis from 4 to 10 years. Of the 17, one died perioperatively from a pulmonary thromboembolism. Fifteen others achieved a complete remission within 3 months of treatment for FSGS recurrence. After a median follow-up period of 4 years, there were no recurrences of significant proteinuria. One patient achieved remission with rituximab., Conclusion: The addition of plasmapheresis and cyclophosphamide to a calcineurin- and steroid-based immunosuppression regime was highly successful in inducing high remission rates with recurrent FSGS. Prospective trials are needed to evaluate further the efficacy of increased immunosuppression along with plasmapheresis in this setting., (© 2022. The Author(s).)

Background: : Glomerular diseases (GDs) and other renal immunologic diseases are an important cause of morbidity and mortality. Providing a single point of service in collaboration with various specialists at a renal immunology clinic for such patients is not novel, but outcomes have not been reported. Here, we report the short-term outcome of Indian patients attending our clinic., Methods: : This single-center prospective cohort study enrolled biopsy-proven immunologically-mediated adults with renal diseases between April 2018 and December 2019, and followed them for six months. The primary end point for the analysis was an incidence of end-stage renal disease (ESRD) or loss of >50% estimated glomerular filtration rate (eGFR) and patient survival at six months. Secondary endpoints were the rate of complete or partial remission, and impact of demographic factors., Results: : Ninety two patients underwent renal biopsy for suspected immunological renal diseases. Fourteen (15.2%) cases were excluded for nonimmune etiologies, whereas 78 (84.7%) confirmed cases of immune etiology were included. Most common primary GD (n = 51) (93.5%) was membranous nephropathy (n = 20) (25.6%), whereas lupus nephritis was the most common (n = 8) (29.6%) secondary GD. Overall, 10 (12.8%) patients reached renal endpoint of ESRD or >50% fall in eGFR. Focal segmental glomerulosclerosis (FSGS) (27%) patients had worst renal outcome. Patient survival was 94.8%. Thirty patients (38.4%) achieved complete, whereas 24 each (30.7%) achieved partial remission and remained resistant to disease specific therapies, respectively. Univariate analysis identified hypertension, severity of hypertension, and resistance to achieve proteinuria remission as significantly associated (P < 0.001) factors with poor renal outcome., Conclusions: : The present study shows that short term renal outcome of Indian patients with renal immune diseases remains poor. FSGS remains the GD with the worst renal outcome. Hypertension, its severity, failure to achieve proteinuria remission were significantly associated with poor renal outcomes.

Background: Steroid-resistant nephrotic syndrome (SRNS) is a major cause of stage 5 chronic kidney disease (CKD 5) in children. LDL apheresis (LDL-A) is now FDA approved for the treatment of pediatric focal segmental glomerulosclerosis (FSGS). Effective management of hyperlipidemia with LDL-A in SRNS patients may prevent progression of kidney disease and lead to remission. We report a case series of patients who received LDL-A for treatment of SRNS METHODS: We describe five children with SRNS who were treated with 12 sessions of LDL-A. Partial remission (PR) is defined as urine protein to creatinine ratio (UPC) of 0.2-2 (g/g) or decrease in UPC ≥ 50%, and complete remission (CR) is defined as UPC < 0.2 (g/g)., Results: One patient achieved CR and three achieved PR. One patient did not respond to therapy. The earliest that a patient achieved PR was at treatment #10 and some did not respond until after LDL-A was completed. Those who responded stayed in either CR or PR for extended periods of time. LDL-A was successful at significantly reducing LDL (p < 0.001), total cholesterol (p < 0.001), and triglyceride (p < 0.001)., Conclusions: LDL-A was able to significantly decrease the lipid levels in these patients and induce CR and PR in the majority. The current study confirms previous studies showing those with a higher glomerular sclerosis burden were less likely to respond. LDL-A should be considered in patients with treatment-resistant SRNS and should be considered before there is a high burden of glomerular sclerosis to provide the best chance of success., (© 2021. IPNA.)

Objectives: Focal segmental glomerulosclerosis recurrence after renal transplant occurs frequently in pediatric patients and is associated with poor graft survival when patients reach adulthood. We investigated recurrence rates, recurrence risk factors, management strategies, and long-term graft function among pediatric renal transplant recipients with focal segmental glomerulosclerosis as primary disease., Materials and Methods: We retrospectively evaluated medical records of 34 pediatric patients with primary focal segmental glomerulosclerosis who had undergone renal transplant between 2004 and 2019 at our center. Focal segmental glomerulosclerosis recurrence was diagnosed by the presence of nephrotic range proteinuria after transplant and confirmed by graft biopsy. Preoperative prophylactic plasma exchange was administered to pediatric renal transplant recipients with primary focal segmental glomerulosclerosis. Plasma exchange was also used to treat focal segmental glomerulosclerosis recurrence, with rituximab added if the patient did not respond to plasma exchange., Results: All patients (male-to-female ratio of 19:15) in our group underwent renal transplant. Mean patient age at the time of transplant was 12.72 ± 5.46 years. Twenty-nine patients received living- related donor allografts (85.3%) and 5 received organs from deceased donors (14.7%). We identified focal segmental glomerulosclerosis recurrence in 5 recipients (14.7%). Time from focal segmental glomerulosclerosis diagnosis to end-stage renal disease and duration of dialysis were shorter in the recurrence group than in the nonrecurrence group (48.4 months [range, 2-90 mo] vs 65.1 months [range, 8-123 mo] and 1.41 ± 0.82 vs 3.18 ± 1.88 years, respectively; P < .05). Donor type and transplant age were similar in both groups. Of those with recurrence who had received plasma exchange and rituximab, 3 patients (75%) had complete remission and 1 patient (25%) had partial remission., Conclusions: Prophylactic plasma exchange and the combined plasma exchange-rituximab regimen for treatment of focal segmental glomerulosclerosis recurrence resulted in low recurrence and good remission rates in our pediatric cohort.

Background: One of the common GN causing ESKD is focal segmental glomerulosclerosis (FSGS). Recurrence of FSGS post-transplantation can lead to graft loss. Data on management either prophylactically or once recurrence occurs are limited. This review article aims to assess the effective management of patients with FSGS recurrence post-transplantation, looking mainly at recurrence post prophylactic treatment and remission in case of treatment post recurrence., Methods: Twenty-three studies were included using the search MeSH terms "FSGS" "recurrence" "adults" "transplantation" "treatment". Search engines used were Pubmed, clinical key, Scopus and Cochrane library. Inclusion criteria were articles covered adult patients with recurrent FSGS post renal transplantation, treatment with rituximab and plasmapheresis, and articles published from 2000 tt2021. Excluded articles were paediatric population, studies with no reported outcomes of the treatment of FSGS, and Patients who received stem cell transplantation or galactose therapy., Results: Prophylactic PP did not show a reduction in recurrence of FSGS in 2/3 studies. Prophylactic rituximab was shown to reduce recurrence of FSGS in one-study and case reports. Treatment of recurrent FSGS with PP showed responses ranging from 41% to 100%. Only one study did not show improvement with PP use as treatment having a 27% remission. Treatment with rituximab showed variable results, with reports showing remission ranging from 57% to 100%. Whereas other reports showing no response at all. PP prescription reporting was variable. One study suggested intensified PP regimen while in most other studies PP was guided by the response reflected by the reduction of proteinuria., Discussion: Reviewing the treatment of recurrent FSGS is crucial, as there no consensus on treating FSGS as the disease is not very common in the adult population. The evidence of different modalities is based on small cohort studies. This paper supports the use of PP and RTX as treatment of recurrent FSGS., Conclusions: In conclusion, PP and RTX are the main modalities to treat recurrent FSGS with varying response rates. Prophylactic PP does not play a role in preventing recurrent FSGS. Prophylactic rituximab might play a role in preventing FSGS post-transplantation. PP and RTX, when used as a treatment, show variable response rates. Larger RCTs are needed to have a strong level of evidence to base our clinical management on., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation (KTx) develops in 40% of patients, leading to graft loss in half of cases. Extracorporeal apheretic treatments, combined with immunosuppressive drugs, seem to be the most promising therapies, but at now limited reports are available, mainly in pediatric patients., Objective: We aimed to assess the efficacy of immunoadsorption (IA) to treat recurrent FSGS in pediatric patients., Methods: We report a case series of 4 pediatric patients (aged 4-12 years) followed at our institution for early recurrent FSGS after KTx. FSGS recurrence was treated with early and intensive apheretic treatments IA., Results: After IA initiation, a partial remission (PR) of proteinuria at 24-month follow-up was achieved only in 1 patient. The others showed a mild reduction of nephrotic proteinuria, without PR, but gained a significant improvement in clinical signs of nephrotic syndrome (reduction of edema, increased serum albumin, and total protein levels). After a median follow-up of 38 (22-48) months, renal function was almost stable over time in all patients, except one who returned to hemodialysis after 22 months. No severe IA-related complications occurred., Conclusions: According to our clinical experience, IA revealed as a safe and effective therapy to treat patients with recurrent FSGS after KTx and it could maintain stable renal function in 75% of patients., (© 2022 S. Karger AG, Basel.)

Recurrence of the primary disease is one of the most common causes of graft failure in the first decade after kidney transplantation. We present a case of a patient with an unusually rapid recurrence of focal segmental glomerulonephritis in the graft, the recognition of its occurrence was hampered by the primary graft affection and oligoanuria and by insignificant histological changes in the first two biopsy samples in the early post-transplant period, as well as by unawareness of the disease leading to terminal renal failure, as no renal biopsy was performed due to grade 3 obesity. Only worsening of hypoalbuminemia and finding of massive proteinuria despite oligoanuria were crucial for further management. Disease recurrence in the graft was confirmed by electron microscopy. However, complex targeted therapy did not result in restoration of graft function and decrease in proteinuria. This case history was aimed to draw attention to the knowledge of the importance of the primary disease confirmed by renal biopsy and early (so called pre-emptive) treatment in case of diseases with a high potential of recurrence (Fig. 7, Ref. 10). Text in PDF www.elis.sk Keywords: kidney transplantation, recurrence, minimal changes in glomeruli, focal segmental glomerulosclerosis.

Background: Although kidney transplantation (KTX) is the treatment of choice for pediatric end stage kidney disease (ESKD); concerns for recurrence in cases of focal segmental glomerulosclerosis (FSGS) are still present. This study aimed to investigate the outcome of KTX in children with ESKD secondary to FSGS, with implementation of preemptive perioperative plasma exchange (PE) for non-genetically proven patients., Methods: Forty FSGS pediatric kidney transplant recipients were studied. Of them: 12 patients (30%) had genetically proven NPHS2 mutations/familial and 28 (70%) were sporadic FSGS patients. All sporadic patients electively received 6 perioperative PE sessions. Patients with recurrence of proteinuria (n = 13; including 3 patients with genetic/familial and 10 patients with sporadic FSGS) were managed with PE and Rituximab (RTX). Kaplan-Meier curves were used to analyze graft and recurrence free survival data., Results: The mean follow-up duration after KTX was 3.8 ± 2.86 years. Recurrence of proteinuria was encountered early postoperative in 11 patients (27.5%) and late (1.6 and 2.9 years after KTX) in 2 patients (5%). All patients with early recurrence achieved complete remission, while patients with late recurrence developed graft failure. Current serum creatinine and proteinuria levels were not different in patients received PE (n = 31) and patients did not PE (n = 9) (p = 0.308 and 0.287 respectively). Current serum creatinine and proteinuria levels in sporadic patients (n = 28) after prophylactic perioperative PE were not different from those of genetic/ familial patients (n = 12) (p = 0.303 and 0.144 respectively). Proteinuria was less in patients underwent native nephrectomy than others immediately postoperative and at assessment (p = 0.002 & 0.0031 respectively). One-year graft and patient survival was 93.8% with a mean 1-year serum creatinine of 0.67 ± 0.25 mg/dl. Three graft losses (7.5%) were due to chronic rejection 3.3, 3.75 and 4.17 years after KTX and 2 patients' mortality (5%) occurred early postoperative (first 2 weeks)., Conclusion: FSGS transplanted children have favorable outcomes with perioperative PE for non-genetically proven cases. Early recurrence after KTX can be successfully managed with PE and RTX., (© 2021. The Author(s).)

Peritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by steroid resistant primary focal segmental glomerulosclerosis, a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed to identify a core list of 40 proteins, with ANXA13 as most promising potential biomarker, to distinguish, in our patient population, peritoneal dialysis effluent exosomes of FSGS from No FSGS patients (with 100% accuracy). Additionally, the Weight Gene Co-expression Network Analysis algorithm identified 17 proteins, with PTP4A1 as the most statistically significant biomarker associated to PD vintage and decreased PM function. Altogether, our data suggest that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery. The role of the proposed biomarkers in the PM pathology deserves further investigation. Our results need further investigations in a larger population to corroborate these findings and investigate a possible increased risk of PM loss of function or development of encapsulating peritoneal sclerosis in FSGS patients, thus to eventually carry out changes in PD treatment and management or implement new solutions., (© 2021. The Author(s).)

Focal segmental glomerulosclerosis (FSGS) is not a specific disease entity but a lesion that primarily targets the podocyte. In a broad sense, the causes of the lesion can be divided into those triggered by a presumed circulating permeability factor, those that occur secondary to a process that might originate outside the kidneys, those caused by a genetic mutation in a podocyte or glomerular basement membrane protein, and those that arise through an as yet unidentifiable process, seemingly unrelated to a circulating permeability factor. A careful attempt to correctly stratify patients with FSGS based on their clinical presentation and pathological findings on kidney biopsy is essential for sound treatment decisions in individual patients. However, it is also essential for the rational design of therapeutic trials in FSGS. Greater recognition of the pathophysiology underlying podocyte stress and damage in FSGS will increase the likelihood that the cause of an FSGS lesion is properly identified and enable stratification of patients in future interventional trials. Such efforts will facilitate the identification of effective therapeutic agents., (© 2021. Springer Nature Limited.)

Objectives: Kidney transplant (KTx) recipients with IgAN as primary disease, were compared with recipients with other causes of renal failure, in terms of long-term outcomes., Methods: Ninety-nine KTx recipients with end-stage kidney disease (ESKD) due to IgAN, were retrospectively compared to; i/ a matched case-control group of patients with non-glomerular causes of ESKD, and ii/ four control groups with ESKD due to glomerular diseases; 44 patients with primary focal segmental glomerulosclerosis (FSGS), 19 with idiopathic membranous nephropathy (IMN), 22 with lupus nephritis (LN) and 21 with pauci-immune glomerulonephritis (PIGN)., Results: At end of the observation period, graft function and survival, were similar between KTx recipients with IgAN and all other groups, but the rate of disease recurrence in the graft differed significantly across groups. The rate of IgAN recurrence in the graft was 23.2%, compared to 59.1% (p<0.0001) in the FSGS group, 42.1% (p = 0.17) in the IMN group, and 0% in the LN and PIGN groups (p = 0.01). IgAN recipients, who were maintained with a regimen containing tacrolimus, experienced recurrence less frequently, compared to those maintained with cyclosporine (p = 0.01). Graft loss attributed to recurrence was significantly higher in patients with FSGS versus all others., Conclusion: Recipients with IgAN as primary disease, experienced outcomes comparable to those of recipients with other causes of ESKD. The rate of IgAN recurrence in the graft was significantly lower than the rate of FSGS recurrence, but higher than the one recorded in recipients with LN or PIGN. Tacrolimus, as part of the KTx maintenance therapy, was associated with lower rates of IgAN recurrence in the graft, compared to the rate cyclosporine., Competing Interests: The authors have declared that no competing interests exist.

Background: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. To date, few studies have investigated predictive factors for treatment responses in recurrent FSGS., Methods: We retrospectively analyzed 16 patients who were < 16 years at the age of onset and had post-transplant recurrence of FSGS from 1993 to 2018. Patients who achieved complete remission or partial remission after initiating therapy for recurrent FSGS were defined as responders. We compared several clinical characteristics between responders and non-responders. Time to remission was also analyzed., Results: Ten patients were responders, and six patients were non-responders. Univariate analysis showed that responders had a significantly lower amount of maximum proteinuria at the time of recurrence (P = 0.015) and more highly selective proteinuria (P = 0.013) than non-responders. The time to remission from initiation of therapy was 2 months (interquartile range 0.2-4.4). In all responders, except for one patient, remission was achieved within 6 months., Conclusions: Therapeutic responses may be predicted by examining the amount and selectivity of proteinuria at the time of recurrence. Further studies with larger numbers of patients are clearly required to validate these findings.

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., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence., (© 2020 Wiley Periodicals LLC.)

The recurrence of primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation (KT) appears in 30 % of the recipients. Sometimes it can cause the loss of the allograft. Although many treatments for this condition have been reported, 20 %-40 % of the affected patients are refractory or presents frequents relapses. In this paper we describe the evolution of three recipients treated with long-term plasmapheresis therapy after a recurrence of FSGS with a bad or incomplete response to other treatments. Although our findings require confirmation, long-term plasmapheresis could be a therapeutic option for this condition., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead to early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, "the" actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that allow us to study FSGS from a yet unexplored angle. Here, we report the successful treatment of recurrent FSGS in a patient after living-related kidney transplantation by removal of circulating factors with CytoSorb apheresis. Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient's serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocytes actin cytoskeleton inducing a functional phenotype and podocyte effacement. We then performed Raman spectroscopy in the < 50 kDa serum fraction, on cultured podocytes treated with the FSGS serum and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence. The analysis revealed changes in podocyte metabolome induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several altered Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which were supported by disturbances in the Raman spectra. Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease.

Recurrence of primary focal and segmental glomerulosclerosis following kidney transplantation (rFSGS) is a frequent and severe disease. We studied the time to recurrence of FSGS and its impact on the response to plasma exchange (PE) and graft survival. 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 and 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. 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., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: Many patients with idiopathic focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation (TX). Although several circulating permeability factors (CPFs) responsible for recurrence have been suggested, there is no consensus. To facilitate CPF identification and predict recurrence after TX, there is a need for robust methods that demonstrate the presence of CPFs., Methods: Cultured human podocytes (hPods) and human and mouse glomerular endothelial cells (ciGEnC, mGEnC) were exposed to plasmas of FSGS patients with presumed CPFs, and of (disease) controls. A visual scoring assay and flow cytometry analysis of side scatter were used to measured changes in cellular granularity after exposure to plasma., Results: Nine out of 13 active disease plasmas of 10 FSGS patients with presumed CPFs induced granularity in hPod in a dose- and time-dependent manner. Corresponding remission plasmas induced no or less granularity in hPod. Similar results were obtained with ciGEnC and mGEnC, although induced granularity was less compared with hPod. Notably, foetal calf serum, healthy plasma and a remission plasma partially blocked FSGS plasma-induced hPod granularity., Conclusions: We developed a novel assay in which active disease, presumably CPF-containing, FSGS plasmas induced granularity in cultured hPod. Our results may indicate the presence of CPF inhibitor(s) in healthy and remission plasma. We suggest the presence of a delicate balance between CPF and a CPF inhibitory factor, which is disturbed in patients with active disease. Our novel assays can be applied in future research to identify CPF and CPF inhibitors, and possibly to predict recurrence after TX., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper.

Evidence for reduced expression of cyclin G associated kinase (GAK) in glomeruli of patients with chronic kidney disease was observed in the Nephroseq human database, and GAK was found to be associated with the decline in kidney function. To examine the role of GAK, a protein that functions to uncoat clathrin during endocytosis, we generated podocyte-specific Gak-knockout mice (Gak-KO), which developed progressive proteinuria and kidney failure with global glomerulosclerosis. We isolated glomeruli from the mice carrying the mutation to perform messenger RNA profiling and unearthed evidence for dysregulated podocyte calpain protease activity as an important contributor to progressive podocyte damage. Treatment with calpain inhibitor III specifically inhibited calpain-1/-2 activities, mitigated the degree of proteinuria and glomerulosclerosis, and led to a striking increase in survival in the Gak-KO mice. Podocyte-specific deletion of Capns1, essential for calpain-1 and calpain-2 activities, also improved proteinuria and glomerulosclerosis in Gak-KO mice. Increased podocyte calpain activity-mediated proteolysis of IκBα resulted in increased NF-κB p65-induced expression of growth arrest and DNA-damage-inducible 45 beta in the Gak-KO mice. Our results suggest that loss of podocyte-associated Gak induces glomerular injury secondary to calcium dysregulation and aberrant calpain activation, which when inhibited, can provide a protective role.

Background: Angiotensin II type 1 receptors (AT1Rs) are expressed on podocytes, endothelial and other cells, and play an essential role in the maintenance of podocyte function and vascular homeostasis. The presence of AT1R antibodies (AT1R-Abs) leads to activation of these receptors resulting in podocyte injury and endothelial cell dysfunction. We assessed the correlation between AT1R-Abs and the risk of post-transplant FSGS., Methods: This is a retrospective study, which included all kidney transplant recipients with positive AT1R-Abs (≥ 9 units/ml), who were transplanted and followed at our center between 2006 and 2016. We assessed the development of biopsy proven FSGS and proteinuria by urine protein to creatinine ratio of ≥1 g/g and reviewed short and long term outcomes., Results: We identified 100 patients with positive AT1R-Abs at the time of kidney transplant biopsy or proteinuria. 49% recipients (FSGS group) had biopsy-proven FSGS and/or proteinuria and 51% did not (non-FSGS group). Pre-transplant hypertension was present in 89% of the FSGS group compared to 72% in the non-FSGS group, p = 0.027. Of the FSGS group, 43% were on angiotensin converting enzyme inhibitors or angiotensin receptor blockers prior to transplantation, compared to 25.5% in the non-FSGS group, p = 0.06. Primary idiopathic FSGS was the cause of ESRD in 20% of the FSGS group, compared to 6% in the non-FSGS group, p = 0.03. The allograft loss was significantly higher in the FSGS group 63% compared to 39% in non-FSGS. Odds ratio and 95% confidence interval were 2.66 (1.18-5.99), p = 0.017., Conclusions: Our data suggest a potential association between AT1R-Abs and post-transplant FSGS leading to worse allograft outcome. Therefore, AT1R-Abs may be considered biomarkers for post-transplant FSGS.

Purpose: To demonstrate the efficacy of combined rituximab and plasmapheresis (PP)/plasma exchange (PE) therapy for focal segmental glomerulosclerosis in transplanted kidneys (ptFSGS)., Methods: We searched MEDLINE, SCOPUS, and Cochrane Library for eligible publications. Only observational studies or clinical trials containing patients' age > 18 years were included for full-text extraction., Results: A total of eight observational studies (n = 85) were included in meta-analyses. With a median follow-up of 18 months (IQR 4.4), combination therapy of RTX-PP/PE in patients with ptFSGS resulted in overall remission rate of 72.7% (95% CI 52.3-86.6%) with a significant reduction of proteinuria and serum creatinine levels. Complete remission was 41.0%, while partial remission was 31.7%. The mean difference of serum creatinine levels between pre- and post-treatment was - 0.65 mg/dL (95% CI - 1.15 to - 0.14). The mean difference of the degree of proteinuria between pre- and post-treatment was - 4.79 g/day (95% CI - 7.02 to - 2.56). Subgroup analyses were performed after adjusted for study year, type of intervention, and primary pre-transplant lesion. Patients with recurrent FSGS tended have lesser reduction in the degree of proteinuria compared to patients with de novo FSGS. Incidence of serious adverse events with combined RTX-PP/PE therapy was 0.12 event/year., Conclusion: We conclude that combined RTX-PP/PE therapy may be considered as an alternative treatment of ptFSGS in achieving remission by lowering proteinuria and serum creatinine levels. However, the efficacy of combined RTX-PP/PE therapy must be confirmed in randomized-controlled trials.

Background and Objectives: Malaria, a potentially life-threatening disease, is the most prevalent endemic infectious disease worldwide. In the modern era, the spectrum of glomerular involvement observed in patients after malarial infections remains poorly described., Design, Setting, Participants, & Measurements: We therefore performed a retrospective multicenter study to assess the clinical, biologic, pathologic, and therapeutic characteristics of patients with glomerular disease demonstrated by kidney biopsy in France within 3 months of an acute malaria episode., Results: We identified 23 patients (12 men), all but 1 of African ancestry and including 10 patients with concomitant HIV infection. All of the imported cases were in French citizens living in France who had recently traveled back to France from an endemic area and developed malaria after their return to France. Eleven patients had to be admitted to an intensive care unit at presentation. Plasmodium falciparum was detected in 22 patients, and Plasmodium malariae was detected in 1 patient. Kidney biopsy was performed after the successful treatment of malaria, a mean of 24 days after initial presentation. At this time, all patients displayed AKI, requiring KRT in 12 patients. Nephrotic syndrome was diagnosed in 17 patients. Pathologic findings included FSGS in 21 patients and minimal change nephrotic syndrome in 2 patients. Among patients with FSGS, 18 had collapsing glomerulopathy (including 9 patients with HIV-associated nephropathy). In four patients, immunohistochemistry with an antibody targeting P. falciparum histidine-rich protein-2 demonstrated the presence of the malaria antigen in tubular cells but not in podocytes or parietal epithelial cells. An analysis of the apoL1 risk genotype showed that high-risk variants were present in all seven patients tested. After a mean follow-up of 23 months, eight patients required KRT (kidney transplantation in two patients), and mean eGFR for the other patients was 51 ml/min per 1.73 m 2 ., Conclusions: In patients of African ancestry, imported Plasmodium infection may be a new causal factor for secondary FSGS, particularly for collapsing glomerulopathy variants in an APOL1 high-risk variant background., (Copyright © 2020 by the American Society of Nephrology.)

Podocyte injury is the initiating step in the pathway toward clinically evident forms of nephrotic syndrome known as podocytopathies, represented as either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). There are hallmark differences in the histologic appearances of MCD and FSGS, which in turn represent distinct pathogenic models after initial podocyte injury (eg, no change in podocyte number in MCD vs podocyte detachment and death in FSGS). However, MCD and FSGS also share a number of common causes, supporting the theory that these diseases lie along a shared podocytopathy spectrum. In this installment of AJKD's Core Curriculum in Nephrology, we demonstrate how the podocytopathies can be classified according to pathogenesis and treatment response as an alternative to histologic description. Using case examples, we show how these alternative classification schemes can assist not only diagnosis, but also long-term management of podocytopathies., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Focal segmental glomerulosclerosis (FSGS) is a rare kidney disease with an annual incidence of 0.2-1.8 cases per 100,000 individuals. Most rare diseases like FSGS lack effective treatments, and it is difficult to implement clinical trials to study rare diseases because of the small sample sizes and difficulty in recruitment. A novel clinical trial design, a small sample, sequential, multiple assignment, randomized trial (snSMART) has been proposed to efficiently identify effective treatments for rare diseases. In this work, we review and expand the snSMART design applied to studying treatments for FSGS. The snSMART is a multistage trial that randomizes participants to one of three active treatments in the first stage and then re-randomizes those who do not respond to the initial treatment to one of the other two treatments in the second stage. A Bayesian joint stage model efficiently shares information across the stages to find the best first stage treatment. In this setting, we modify the previously presented design and methods (Wei et al. 2018) such that the proposed design includes a standard of care as opposed to three active treatments. We present Bayesian and frequentist models to compare the two novel therapies to the standard of care. Additionally, we show for the first time how we should estimate and compare tailored sequences of treatments or dynamic treatment regimens (DTRs) and contrast the results from our methods to existing methods for analyzing DTRs from a SMART. We also propose a sample size calculation method for our snSMART design when implementing the frequentist model with Dunnett's correction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) is associated with a slower progression to end-stage renal disease (ESRD) in pre-dialysis patients. However, little is known about the associated mortality risks after transitioning to dialysis., Methods: This retrospective cohort study included 0-21 year-old incident dialysis patients from the United States Renal Data System starting dialysis between 1995 and 2016. We examined the association of CAKUT vs. non-CAKUT with all-cause mortality, using Cox regression adjusted for case mix variables. We also examined the mortality risk associated with 14 non-CAKUT vs. CAKUT ESRD etiologies and under stratification by estimated glomerular filtration rate (eGFR)., Results: Among 25,761 patients, the median (interquartile range) age was 17 (11-19) years, and 4780 (19%) had CAKUT. CAKUT was associated with lower mortality, with an adjusted hazard ratio (aHR) of 0.72 (95%CI, 0.64-0.81) (reference: non-CAKUT). In age-stratified analyses, CAKUT vs. non-CAKUT aHRs (95%CI) were 0.66 (0.54-0.80), 0.56 (0.39-0.80), 0.66 (0.50-0.86), and 0.97 (0.80-1.18) among patients < 6, 6-< 13, 13-< 18, and ≥ 18 years at dialysis initiation, respectively. Among non-CAKUT ESRD etiologies, the risk of mortality associated with primary glomerulonephritis (aHR, 0.93; 95%CI 0.80-1.09) and focal segmental glomerulosclerosis (aHR, 0.89; 95%CI, 0.75-1.04) were comparable or slightly lower compared to CAKUT, whereas most other primary causes were associated with higher mortality risk. While the CAKUT group had lower mortality risk compared to the non-CAKUT group patients with eGFR ≥5 mL/min/1.73m 2 , CAKUT was associated with higher mortality in patients with eGFR < 5 mL/min/1.73 m 2 ., Conclusions: CAKUT is associated with lower mortality among children < 18 years old, but showed comparable mortality with non-CAKUT among patients ≥ 18 years old. ESRD etiology should be considered in risk assessment for children initiating dialysis.

Background: Idiopathic focal segmental glomerulosclerosis (FSGS) commonly recurs in the early post-transplant period. The treatment protocols and results are conflictive in recurrent FSGS. We aimed to present the results of our treatment protocol and basic approach to the disease recurrences., Methods: This prospective, single-center study was conducted between the years 2015 and 2018. Twelve patients who fit completely the diagnosis of idiopathic FSGS by clinical, laboratory, and biopsy findings were included. A specific treatment protocol which consists of plasma exchange and high dose intravenous cyclosporine was delivered to the patients independently of induction protocols. Twenty-four months of outcomes of graft functions were evaluated., Results: Nine patients completed the treatment protocol and were documented for evaluation. All patients achieved a complete or partial remission in an average 24 months of follow-up period., Conclusion: Idiopathic FSGS is more commonly recurrent than thought to be. The early detection of proteinuria is crucial because the administration of a plasma exchange-based treatment protocol can reverse proteinuria. We think our treatment protocol is a well-established, efficient, and safe choice for post-transplant recurrent FSGS in adults., (Copyright © 2020 Elsevier Inc. All rights reserved.)

There are more than 150 different rare genetic kidney diseases. They can be classified according to diagnostic findings as (i) disorders of growth and structure, (ii) glomerular diseases, (iii) tubular, and (iv) metabolic diseases. In recent years, there has been a shift of paradigm in this field. Molecular testing has become more accessible, our understanding of the underlying pathophysiologic mechanisms of these diseases has evolved, and new therapeutic strategies have become more available. Therefore, the role of nephrologists has progressively shifted from a mere spectator to an active player, part of a multidisciplinary team in the diagnosis and treatment of these disorders. This article provides an overview of the recent advances in rare hereditary kidney disorders by discussing the genetic aspects, clinical manifestations, diagnostic, and therapeutic approaches of some of these disorders, named familial focal and segmental glomerulosclerosis, tuberous sclerosis complex, Fabry nephropathy, and MYH-9 related disorder.

Focal segmental glomerulosclerosis (FSGS) is the most common cause of adult nephrotic syndrome in USA. Its mechanisms remain unclear and the effective treatment lacks. We previously reported that upregulation of microRNA (miR)-150 in human podocytes increases profibrotic proteins and decreases anti-fibrotic suppressor of cytokine signaling 1 (SOCS1). We aimed to clarify whether miR-150 inhibitor can ameliorate glomerular injury and to identify its corresponding mechanisms in adriamycin-induced FSGS mice. We found that renal miR-150 increased in adriamycin-induced FSGS mice and FAM-labeled locked nucleic acid-anti-miR-150 (LNA-anti-miR-150) was absorbed by the animal kidneys 6 h after subcutaneous injection. The administration of LNA-anti-miR-150 (2 mg/kg BW twice weekly for 6 w) inhibited renal miR-150 levels without systemic toxicity. With renal miR-150 inhibition, proteinuria, hypoalbuminemia, and hyperlipemia were ameliorated in FSGS mice compared to the scrambled LNA. Meanwhile, the elevated profibrotic proteins and proinflammatory cytokines, decreased antifibrotic SOCS1, and the filtration of T cells in FSGS mice were reverted by LNA-anti-miR-150. Finally, we found that miR-150 most located on podocytes in renal biopsies of FSGS patients. We conclude that LNA-anti-miR-150 might be a novel promising therapeutic agent for FSGS. The renal protective mechanisms might be mediated by anti-fibrosis and anti-inflammation as well as reducing infiltration of T cells in the kidney., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Primary focal and segmental glomerulosclerosis (FSGS) frequently reoccurs on kidney transplants and may lead to premature allograft loss. There are no guidelines for treating FSGS recurrence on allografts; treatment is based on apheresis (plasma exchange plasmapheresis [PP], semi-specific immunoadsorption [IA] with reusable columns) plus rituximab., Objective: We aimed to assess the efficacy of IA to treat recurrent FSGS., Methods: We report on 7 patients with recurrent FSGS on kidney allograft (proteinuria ≥3 g/g of urinary creatinine or ≥3 g/day); they all received IA. Our primary objective was to reduce proteinuria by >50%. Patients' mean age was 45 ± 10 years. Postoperative immunosuppression relied on steroids, mycophenolate mofetil, tacrolimus, with an induction therapy of basiliximab or antithymocyte globulins. Prophylaxis to prevent FSGS recurrence was either rituximab alone (n = 3), rituximab plus either PP or IA (n = 3), or no treatment (n = 1). Mean follow-up was 20 ± 13 months. There was a median of 72 (14-101) IA sessions per patient, that is, a mean of 14 ± 1 sessions per IA column., Results: At 12 months after starting IA, all patients had partial (n = 6) or complete (n = 1) remission, and allograft survival was 100%. The mean reduction in proteinuria within an IA session was 45 ± 15%. At last follow-up, 2 patients are in remission without IA, 3 patients are in partial remission that is IA dependent, and 2 patients lost their allograft due to FSGS recurrence. The most frequent adverse event was cytomegalovirus reactivation (n = 13), which subsided after valganciclovir therapy., Conclusions: We show that recurrence of FSGS can be controlled long term with IA plus rituximab. However, some patients remained dependent on IA., (© 2020 S. Karger AG, Basel.)

Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular injury, rather than a single disease, that is caused by diverse clinicopathological entities with different mechanisms of injury with the podocyte as the principal target of lesion, leading to the characteristic sclerotic lesions in parts (i.e., focal) of some (i.e., segmental) glomeruli. The lesion of FSGS has shown an increasing prevalence over the past few decades and is considered the most common glomerular cause leading to ESKD. Primary FSGS, which usually presents with nephrotic syndrome, is thought to be caused by circulating permeability factors that have a main role in podocyte foot process effacement. Secondary forms of FSGS include maladaptive FSGS secondary to glomerular hyperfiltration such as in obesity or in cases of loss in nephron mass, virus-associated FSGS, and drug-associated FSGS that can result in direct podocyte injury. Genetic FSGS is increasingly been recognized and a careful evaluation of patients with atypical primary or secondary FSGS should be performed to exclude genetic causes. Unlike primary FSGS, secondary and genetic forms of FSGS do not respond to immunosuppression and tend not to recur after kidney transplantation. Distinguishing primary FSGS from secondary and genetic causes has a prognostic significance and is crucial for an appropriate management. In this review, we examine the pathogenesis, clinical approach to distinguish between the different causes, and current recommendations in the management of FSGS., (© 2020 S. Karger AG, Basel.)

Focal segmental glomerulosclerosis (FSGS) is one of the most frequent and severe glomerular kidney disease with frequent progression to end-stage renal disease and a high rate of recurrence in renal transplantations. Due to intolerance or resistance to the current immunomodulatory treatments, the management of FSGS is a therapeutic challenge. Over the last few years, development in extracorporeal therapies has shown potential beneficial outcomes in drug-resistant and recurrent FSGS patients. Thus, this study reviews the current literature on the use of extracorporeal therapies, such as plasma exchange therapy, immunoadsorption, and low-density lipoprotein apheresis, for the treatment of FSGS in the pediatric population., (© 2020 S. Karger AG, Basel.)