• Urinary CD80
• mild pathological change
• primary focal segmental glomerulosclerosis
• severe clinical manifestations
• steroid-dependent

• Child
• Adult
• Humans
• Nephrosis, Lipoid/complications
• Glomerulosclerosis, Focal Segmental/pathology
• Retrospective Studies
• B7-1 Antigen/therapeutic use
• B7-1 Antigen/urine
• Nephrotic Syndrome/etiology
• Recurrence
• Steroids/therapeutic use

• B cell
• T cell
• complement
• glomerulonephritis
• immunomodulation

• Humans
• Immunomodulating Agents
• Immunity, Innate
• Kidney
• Kidney Diseases/drug therapy
• Adaptive Immunity

• J 4664 Austrian Science Fund FWF

• CD20
• CD38
• daratumumab
• focal segmental glomerulosclerosis
• minimal change disease of
• nephrotic syndrome
• rituximab

• Child
• Humans
• Biological Products
• Nephrotic Syndrome/drug therapy
• Rituximab/therapeutic use
• Abatacept
• Kidney Failure, Chronic

• adaptive immunity
• immune pathway
• innate immunity
• kidney
• podocyte

• Humans
• Podocytes/metabolism
• Glomerulosclerosis, Focal Segmental/drug therapy
• Kidney Glomerulus
• Nephrotic Syndrome
• Adaptive Immunity

• R01 DK090316 NIDDK NIH HHS

• Abatacept
• B7-1
• Focal segmental glomerulosclerosis
• Kidney transplantation
• Nephrotic syndrome
• Podocyte
• Proteinuria

• kidney diseases
• cell biology

• Humans
• beta Catenin/genetics
• beta Catenin/metabolism
• Chromatography, Liquid
• HSP90 Heat-Shock Proteins/genetics
• HSP90 Heat-Shock Proteins/metabolism
• Kidney Diseases/metabolism
• Low Density Lipoprotein Receptor-Related Protein-5/metabolism
• Molecular Chaperones/metabolism
• Molecular Docking Simulation
• Podocytes/metabolism
• Tandem Mass Spectrometry

• National Natural Science Foundation of China (National Science Foundation of China)
• National Key R&D Program of China 2020YFC2005000; The project of Innovation team of chronic kidney disease with integrated traditional Chinese and Western Medicine 2019KCXTD014; Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory 2018GZR110105004; Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory 2018GZR110102004.

• Immune checkpoint protein (ICP)
• Prognosis
• Soluble CD80

• B7-1 Antigen/metabolism
• Cell Adhesion Molecules
• Humans
• Prognosis
• Sarcoma
• Soft Tissue Neoplasms

• Abatacept
• Adrenocorticotropic hormone
• Calcineurin inhibitors
• Glucocorticoids
• Mycophenolate mofetil
• Podocyte
• Rituximab

• Calcineurin Inhibitors/pharmacology
• Calcineurin Inhibitors/therapeutic use
• Humans
• Immunosuppressive Agents/pharmacology
• Immunosuppressive Agents/therapeutic use
• Kidney Diseases/drug therapy
• Podocytes
• Proteinuria/drug therapy

• circulating factor
• immune cell
• minimal change disease
• nephrotic syndrome
• podocyte
• proteinuria

• Idiopathic nephrotic syndrome
• children
• focal segmental glomerulosclerosis
• podocyte
• proteinuria
• steroid therapy

• Acute kidney injury
• Chronic kidney disease
• Inflammation
• Kynurenine
• Tryptophan
• Uremia

• Acute Kidney Injury/etiology
• Animals
• Humans
• Kynurenine/physiology
• Renal Insufficiency, Chronic/etiology

Nephrotic syndrome (NS) is relatively common in children, with most of its histological types being minimal changed disease. Its etiology has long been attributed to lymphocyte (especially T-cell) dysfunction, while T-cell-mediated vascular hyperpermeability increases protein permeability in glomerular capillaries, leading to proteinuria and hypoproteinemia. Based on this etiology, steroids and immunosuppressive drugs that are effective against this disease have also been considered to correct T-cell dysfunction. However, in recent years, this has been questioned. The primary cause of NS has been considered damage to glomerular epithelial cells and podocyte-related proteins. Therefore, we first describe the changes in expression of molecules involved in NS etiology, and then describe the mechanism by which abnormal expression of these molecules induces proteinuria. Finally, we consider the mechanism by which infection causes the recurrence of NS.

• Nephrotic syndrome
• Gene
• Immunity
• Viral infection
• Children

• Children
• MPGN
• Membranous nephropathy
• Nephrotic syndrome
• Predictive biomarkers
• Prognostic biomarkers

Minimal change disease (MCD) is the most common cause of idiopathic nephrotic syndrome in children, and it is well known for its multifactorial causes which are the manifestation of the disease. Proteinuria is an early consequence of podocyte injury and a typical sign of kidney disease. Steroid-sensitive patients react well with glucocorticoids, but there is a high chance of multiple relapses. CD80, also known as B7-1, is generally expressed on antigen-presenting cells (APCs) in steroid-sensitive MCD patients. Various glomerular disease models associated with proteinuria demonstrated that the detection of CD80 with the increase of urinary CD80 was strongly associated closely with frequent-relapse MCD patients. The role of CD80 in MCD became controversial because one contradicts finding. This review covers the treatment alternatives for MCD with the insight of CD80 as a potential therapeutic target. The promising effectiveness of CD20 (rituximab) antibody and CD80 inhibitor (abatacept) encourages further investigation of CD80 as a therapeutic target in frequent-relapse MCD patients. Therapeutic-based antibody towards CD80 (galiximab) had never been investigated in MCD or any kidney-related disease; hence, the role of CD80 is still undetermined. A new therapeutic approach towards MCD is essential to provide broader effective treatment options besides the general immunosuppressive agents with gruesome adverse effects.

• FSGS
• idiopathic nephrotic syndrome
• immunity
• permeability factor
• podocytopathy

• Biomarker
• CD80
• Glomerular endothelial cell
• Nephrotic syndrome
• Podocyte

Minimal change disease (MCD) is a common form of nephrotic syndrome in adults. However, the molecular mechanism underlying the pathogenesis of MCD remains incompletely understood. In this study, we aimed to investigate the role of the cytokines expression of Th1/Th2/Th17 and urinary CD80 excretion in adult-onset MCD patients.

The lymphocyte subsets, 34 cytokine levels of Th1/Th2/Th17, serum and urine concentrations of CD80, and expression of CD80 in glomeruli were analyzed in 28 cases (15 males and 13 females; average age: 34.1 years, age range: 18–56 years), including 10 patients with MCD in relapse, nine patients with MCD in remission and nine healthy controls.

There was no significant difference of CD3⁺CD4⁺ cells proportion among patients with MCD in relapse, MCD in remission and healthy controls (P = 0.802). The cytokine levels of GM-CSF and tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) in patients with MCD in relapse increased 1.5 times higher than those in remission. An evident increase in the excretion of urinary CD80 was found in patients with relapsed MCD compared with those in remission (598.4 ± 115.8 vs 81.78 ± 7.04 ng/g creatinine, P < 0.001) and healthy controls (598.4 ± 115.8 vs 67.44 ±  8.94  ng/g creatinine, P < 0.001). CD80 expression was observed in podocyte of MCD patient in relapse by immunofluorescence technique.

The cytokines GM-CSF and TRANCE are increased and the urinary CD80 levels are elevated in adult-onset MCD patients in relapse, indicating a disorder of Th1/Th2/Th17 balance and that the elevated excretion of CD80 may underlie the pathogenesis and development of adult-onset MCD.

• Adult-onset minimal change disease
• CD80
• Th1/Th2/Th17

Heterogeneity of nephrotic diseases and a lack of validated biomarkers limits interventions and reduces the ability to examine outcomes. Urinary CD80 is a potential biomarker for minimal change disease (MCD) steroid-sensitive nephrotic syndrome (NS). We investigated and validated a CD80 enzyme-linked immunosorbent assay (ELISA) in urine in a large cohort with a variety of nephrotic diseases.

A commercial CD80 ELISA was enhanced and analytically validated for urine. Patients were from Mayo Clinic (307) and Nephrotic Syndrome Study Network Consortium (NEPTUNE; 104) as follows: minimal change disease (MCD, 56), focal segmental glomerulosclerosis (FSGS, 92), lupus nephritis (LN, 25), IgA nephropathy (IgAN, 20), membranous nephropathy (MN, 49), autosomal dominant polycystic kidney disease (ADPKD, 10), diabetic nephropathy (DN; 106), pyuria (19), and controls (34). Analysis was by Kruskal−Wallis test, generalized estimating equation (GEE) models, and receiver operating characteristic (AUC) curve.

Urinary CD80/creatinine values were highest in MCD compared to other glomerular diseases and were increased in DN with proteinuria >2 compared to controls (control = 36 ng/g; MCD = 139 ng/g, P < 0.01; LN = 90 ng/g, P < 0.12; FSGS = 66 ng/g, P = 0.18; DN = 63, P = 0.03; MN = 69 ng/g, P = 0.33; ng/g, P = 0.07; IgA = 19 ng/g, P = 0.09; ADPKD = 42, P = 0.36; and pyuria 31, P = 0.20; GEE, median, P vs. control). In proteinuric patients, CD80 concentration appears to be independent of proteinuria levels, suggesting that it is unrelated to nonspecific passage across the glomeruli. CD80/creatinine values were higher in paired relapse versus remission cases of MCD and FSGS (P < 0.0001, GEE).

Using a validated ELISA, urinary CD80 levels discriminate MCD from other forms of NS (FSGS, DN, IgA, MN) and primary from secondary FSGS.

• CD80
• focal segmental glomerulosclerosis
• lupus nephritis
• minimial change disease
• nephrotic syndrome

• U54 DK083912 NIDDK NIH HHS
• UL1 TR002240 NCATS NIH HHS
• UL1 TR002548 NCATS NIH HHS

• Diagnosis
• Focal segmental glomerulosclerosis
• Treatment

This study is aimed at investigating the efficacy of CTLA4-Ig abatacept in normalizing proteinuria and its possible mechanism in adriamycin-induced nephropathy (AIN) rats.

A total of 32 healthy male Sprague-Dawley rats were randomly divided into a normal group, an AIN group, an abatacept group, and a prednisone group. Adriamycin (6.5 mg/kg) was injected once via the tail vein of rats to induce nephrotic syndrome. After adriamycin treatment, the abatacept group rats were given abatacept (0.5 mg/kg) once by intraperitoneal injection on day 14. In addition, the prednisone group rats were given prednisone (12.5 mg/kg) daily consecutively by gavage from day 14 to day 21. Blood, urine, and kidney tissue specimens were collected when sacrificed on day 21. The 24-hour urinary protein, serum albumin, cholesterol, creatinine, and urea nitrogen were then detected. An enzyme-linked immunosorbent assay was used to determine the level of urine CD80 and serum IL-17. Flow cytometry was used to investigate the prevalence of circulating Treg. Hematoxylin-eosin staining and electron microscopy were used for a renal histological study. Immunofluorescence staining was performed to confirm the CD80 expression of renal tissue.

The 24-hour urinary protein of the abatacept group was significantly lower than that of the prednisone group and the AIN group. The level of urine CD80 of the abatacept group was significantly lower than that of the AIN group. Compared with the AIN group and the prednisone group, the circulating Treg prevalence of the abatacept group was significantly higher, while the level of serum IL-17 was lower. A negative kidney staining of CD80 expression was demonstrated in each group in this study. The 24-hour urinary protein had a negative correlation with the circulating Treg prevalence and Treg/IL-17 and a positive correlation with the urine CD80 and serum IL-17. Urinary CD80 had a positive correlation with serum IL-17 and no correlation with the circulating Treg prevalence.

CTLA4-Ig abatacept can reduce proteinuria of adriamycin-induced nephropathy rats, possibly at least partially as a result of regulating circulating Treg/IL-17. CTLA4-Ig abatacept could be a promising regimen for idiopathic nephrotic syndrome.

• CD80
• FOXP3
• childhood
• nephrotic syndrome
• regulatory T cell

• Cytotoxic T-lymphocyte-associated antigen-4
• Glomerulonephritides, kidney function

• Adult
• Aged
• Antigens, CD/metabolism
• CTLA-4 Antigen/blood
• CTLA-4 Antigen/genetics
• CTLA-4 Antigen/metabolism
• Female
• Gene Expression Regulation
• Glomerulonephritis/immunology
• Glomerulonephritis/physiopathology
• Humans
• Immunoglobulins/blood
• Kidney/physiopathology
• Lymphocyte Activation
• Lymphocyte Count
• Lymphocyte Subsets/immunology
• Lymphocyte Subsets/metabolism
• Male
• Middle Aged
• ROC Curve
• Young Adult

• UMO-2016/23/B/NZ6/02844 Narodowe Centrum Nauki
• DS460 Uniwersytet Medyczny w Lublinie

The prevalence, pathogenesis, predictors, and natural course of patients with recurrent glomerulonephritis (GN) occurring after kidney transplantation remains incompletely understood, including whether there are differences in the outcomes and advances in the treatment options of specific GN subtypes, including those with de novo GN. Consequently, the treatment options and approaches to recurrent disease are largely extrapolated from the general population, with responses to these treatments in those with recurrent or de novo GN post-transplantation poorly described. Given a greater understanding of the pathogenesis of GN and the development of novel treatment options, it is conceivable that these advances will result in an improved structure in the future management of patients with recurrent or de novo GN. This review focuses on the incidence, genetics, characteristics, clinical course, and risk of allograft failure of patients with recurrent or de novo GN after kidney transplantation, ascertaining potential disparities between “high risk” disease subtypes of IgA nephropathy, idiopathic membranous glomerulonephritis, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis. We will examine in detail the management of patients with high risk GN, including the pre-transplant assessment, post-transplant monitoring, and the available treatment options for disease recurrence. Given the relative paucity of data of patients with recurrent and de novo GN after kidney transplantation, a global effort in collecting comprehensive in-depth data of patients with recurrent and de novo GN as well as novel trial design to test the efficacy of specific treatment strategy in large scale multicenter randomized controlled trials are essential to address the knowledge deficiency in this disease.

• allograft failure
• de novo glomerulonephritis
• glomerulonephritis
• kidney transplantation
• recurrent disease
• recurrent glomerulonephritis

• biomarkers
• focal segmental glomerulosclerosis
• minimal change disease
• nephrotic syndrome
• steroid resistance

• FSGS
• Focal and segmental glomerulosclerosis
• MCD
• minimal change disease
• nephrotic syndrome
• novel therapies

• Adult
• Animals
• Antibodies, Monoclonal/therapeutic use
• Child
• Drug Design
• Drug Resistance, Multiple
• Glomerulosclerosis, Focal Segmental/complications
• Glomerulosclerosis, Focal Segmental/drug therapy
• Humans
• Immunologic Factors/therapeutic use
• Immunosuppressive Agents/therapeutic use
• Nephrosis, Lipoid/complications
• Nephrosis, Lipoid/drug therapy
• Nephrosis, Lipoid/therapy
• Nephrotic Syndrome/etiology
• Nephrotic Syndrome/prevention & control
• Practice Guidelines as Topic
• Proteinuria/drug therapy
• Proteinuria/physiopathology
• Rituximab/therapeutic use

Minimal change disease (MCD) is a form of idiopathic nephrotic syndrome. Compared to children, adult-onset MCD patients are reported to have delayed responses to glucocorticoid treatment. Several studies of children have suggested detecting urinary CD80 levels to diagnose MCD. There are no effective diagnostic methods to distinguish steroid-sensitive MCD from steroid-resistant MCD unless treatments are used.

In a total of 55 patients with biopsy-proven MCD and 26 patients with biopsy-proven idiopathic membranous nephropathy, CD80 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in serum, urine and renal tissue were analyzed.

Steroid-sensitive MCD patients in remission had lower urinary CD80 levels and higher CTLA-4 levels than patients in relapse (156.65 ± 24.62 vs 1066.40 ± 176.76 ng/g creatinine; p < 0.0001), (728.73 ± 89.93 vs 151.70 ± 27.01 ng/g creatinine; p < 0.0001). For MCD patients in relapse, mean urinary CD80 level was higher, and CTLA-4 level was lower for those who were steroid-sensitive than those who were steroid-resistant (1066.40 ± 176.76 vs. 203.78 ± 30.65 ng/g creatinine; p < 0.0001), but the mean urinary CTLA-4 level was lower (151.70 ± 27.01 vs. 457.83 ± 99.45 ng/g creatinine; p < 0.0001). CD80 expression in glomeruli was a sensitive marker to diagnose MCD. The absent or minimal expression of CTLA-4 in glomeruli could distinguish steroid-sensitive MCD from steroid-resistant MCD.

Glucocorticoid treatment may result in complete remission for only MCD patients with strongly positive CD80 expression and negative CTLA-4 expression in glomeruli, or higher urinary CD80 level and lower CTLA-4 level.

• CD80
• Cytotoxic T-lymphocyte antigen-4
• Idiopathic nephrotic syndrome
• Minimal change disease

• disease recurrence
• focal segmental glomerulosclerosis
• kidney transplant
• outcomes
• treatment

• CD80
• Focal segmental glomerulosclerosis
• Minimal change disease
• Nephrotic syndrome

• Adrenal Cortex Hormones
• B7-1 Antigen
• Biomarkers
• Child
• Glomerulosclerosis, Focal Segmental
• Humans
• Nephrosis, Lipoid
• Nephrotic Syndrome

• R01 DK108859 NIDDK NIH HHS
• K01 DK095930 NIDDK NIH HHS
• K12 HD028820 NICHD NIH HHS
• P30 DK048520 NIDDK NIH HHS
• R01 DK108408 NIDDK NIH HHS

• CD80
• kidney transplantation
• large animal model
• proteinuria
• xenograft

• Bis-T-23
• actin
• dynamin
• podocytes

Considerable shortages in the supply of available organs continue to plague the field of solid organ transplantation. Despite changes in allocation, as well as the utilization of extended criteria and living donors, the number of patients waiting for organs continues to grow at an alarming pace. Xenotransplantation, cross-species solid organ transplantation, offers one potential solution to this dilemma. Previous extensive research dedicated to this field has allowed for resolution of xenograft failure due to acute rejection, leaving new areas of unresolved challenges as barriers to success in large animal models. Specific to kidney xenotransplantation, recent data seems to indicate that graft compromise can occur due to discrepancies in growth between breeds of donors and significant proteinuria leading to nephrotic syndrome in the recipient. Given these potential limitations, herein, we review potential pathways behind proteinuria, as well as potential causative factors related to growth discrepancies. Control of both of these has the potential to allow xenotransplantation to become clinically applicable in an effort to resolve this organ shortage crisis.

In view of the availability of new immunosuppression strategies, the recurrence of allograft glomerulonephritis (GN) are reported to be increasing with time post transplantation. Recent advances in understanding the pathogenesis of the GN recurrent disease provided a better chance to develop new strategies to deal with the GN recurrence. Recurrent GN diseases manifest with a variable course, stubborn behavior, and poor response to therapy. Some types of GN lead to rapid decline of kidney function resulting in a frustrating return to maintenance dialysis. This subgroup of aggressive diseases actually requires intensive efforts to ascertain their pathogenesis so that strategy could be implemented for better allograft survival. Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis after renal transplantation was evaluated using data from various registries, and pathogenesis of individual glomerulonephritis is discussed. The following review is aimed to define current protocols of the recurrent primary glomerulonephritis therapy.

• Recurrent glomerulonephritis
• Renal transplantation
• Primary glomerulonephritis

• albuminuria
• chronic kidney disease
• glomerular disease
• podocyte
• proteinuria

• R01 DK095045 NIDDK NIH HHS
• R01 DK099465 NIDDK NIH HHS
• UL1 TR001445 NCATS NIH HHS

• Focal segmental glomerulosclerosis
• Genetic testing
• Glomerular filtration barrier
• Minimal change disease
• Podocyte
• Steroid-resistant nephrotic syndrome

• Actin cytoskeleton
• Podocyts
• Podocyturia
• Urinary podocyte mRNAs
• Urinary podocyte proteins

The etiology of nephrotic syndrome is complex and ranges from primary glomerulonephritis to secondary forms. Patients with nephrotic syndrome often need immunosuppressive treatment with its side effects and may progress to end stage renal disease. This review focuses on recent advances in the treatment of primary causes of nephrotic syndrome (idiopathic membranous nephropathy (iMN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS)) since the publication of the KDIGO guidelines in 2012. Current treatment recommendations are mostly based on randomized controlled trials (RCTs) in children, small RCTs, or case series in adults. Recently, only a few new RCTs have been published, such as the Gemritux trial evaluating rituximab treatment versus supportive antiproteinuric and antihypertensive therapy in iMN. Many RCTs are ongoing for iMN, MCD, and FSGS that will provide further information on the effectiveness of different treatment options for the causative disease. In addition to reviewing recent clinical studies, we provide insight into potential new targets for the treatment of nephrotic syndrome from recent basic science publications.

Recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation occurs in up to 20–50% of FSGS patients and is associated with inferior allograft survival. Treatment of both primary FSGS as well as recurrent FSGS after transplantation with plasma exchange and immunosuppression is often unsuccessful and remains a major challenge as the disease still leads to end-stage renal disease and decreased graft survival. Previous case reports have described patients with recurrent FSGS who were successfully treated with a B7-1 inhibitor (abatacept) inducing partial or complete remission. The rational basis for believing in abatacept as a new therapeutic drug for the treatment of FSGS is the study by Yu et al. [N Engl J Med 2013;369: 2416–2423] showing B7-1 in immunostainings of the podocytes. The authors speculated that B7-1 immunostaining of renal biopsies might identify a subgroup of patients who would benefit from abatacept treatment. We present a case with recurrent FSGS after renal transplantation. The patient was unsuccessfully treated with B7-1 inhibitors. Although the patient was treated with abatacept 10 mg/kg body weight twice, the proteinuria and decreased graft function remained unchanged, and he never reached remission.

• Abatacept
• B7-1 inhibitor
• Focal segmental glomerulosclerosis
• Recurrent focal segmental glomerulosclerosis

• Angiopoietin-like 4
• CD80
• Minimal change disease
• Nephrin phosphorylation
• Podocytopathy

• Adult
• Diagnosis, Differential
• Disease Progression
• Glomerulonephritis/diagnosis
• Glomerulonephritis/etiology
• Glomerulonephritis/therapy
• Glomerulonephritis, IGA/diagnosis
• Glomerulonephritis, IGA/etiology
• Glomerulonephritis, IGA/therapy
• Glomerulonephritis, Membranoproliferative/diagnosis
• Glomerulonephritis, Membranoproliferative/etiology
• Glomerulonephritis, Membranoproliferative/therapy
• Humans
• Nephrosis, Lipoid/etiology
• Practice Guidelines as Topic
• Risk Factors

Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease and a common pathologic diagnosis of idiopathic nephrotic syndrome (NS), especially in steroid-resistant cases. FSGS is known to recur after kidney transplantation, frequently followed by graft loss. However, not all patients with FSGS suffer from recurrence after kidney transplantation, and genetic and secondary FSGS have a negligible risk of recurrence. Furthermore, many cases of recurrence achieve remission with the current management of recurrence (intensive plasmapheresis/immunosuppression, including rituximab), and other promising agents are being evaluated. Therefore, a pathologic diagnosis of FSGS itself should not cause postponement of allograft kidney transplantation. For patients with a high risk of recurrence who presented with classical symptoms of NS, that is, severe edema, proteinuria, and hypoalbuminemia, close monitoring of proteinuria is necessary, followed by immediate, intensive treatment for recurrence.

Recurrence of focal segmental glomerulosclerosis (FSGS) in the allograft occurs in 30–50% of patients, and it is associated with poor renal allograft survival. Major risk factors for recurrence are younger age at diagnosis, rapid progression to end-stage renal disease, white race, and the loss of previous allografts due to recurrence. Recent data support the hypothesis that circulating permeability factors play a crucial role in podocyte injury and progression of FSGS. Due to lack of controlled trials, the management of recurrent FSGS is inconsistent and highly empirical. Prophylactic and perioperative treatment with plasmapheresis and high-dose (intravenous) cyclosporine represent the main cornerstones of immunosuppressive therapy. In recent years, therapy with rituximab has shown promising results. Despite evidence of activation of the renin-angiotensin system (RAS) in recurrent FSGS and its association with progression, only limited data exist on the renoprotective role of RAS blockade in this setting. Further well designed studies are needed on pathogenesis risk factors and therapeutical options in FSGS and its recurrence after transplantation.