Nephrotic Syndrome In Adults Research Articles

Membranous glomerulopathy in women: clinical repercussions

Introduction: Membranous glomerulopathy is one of the most common causes of nephrotic syndrome in adults, with particular prevalence in women. This condition is characterized by thickening of the glomerular basement membrane, resulting in significant proteinuria and other clinical complications. The disease may have primary etiologies, such as the presence of antibodies against the phospholipase A2 receptor, or secondary to conditions such as infections, neoplasias and autoimmune diseases. In women, the clinical repercussions of membranous glomerulopathy may be more complex, since the interaction between hormones and immunological factors may influence the course of the disease and the response to treatment. Methodology: The research was conducted using the PRISMA checklist, with data collection from articles published in the last 10 years in the PubMed, SciELO and Web of Science databases. Five descriptors were used: "membranous glomerulopathy", "nephrotic syndrome", "women", "treatment" and "clinical implications". Inclusion criteria consisted of studies that addressed membranous glomerulopathy specifically in women, articles that presented clinical data, and peer-reviewed studies. Exclusion criteria included publications not related to the female population, articles with insufficient data, and non-original reviews. Results: The review revealed that membranous glomerulopathy in women is associated with a higher incidence of complications, including venous thrombosis and arterial hypertension. Treatments ranged from immunosuppressive to targeted therapies, with varied results in terms of remission and adverse effects. The quality of life of patients was significantly affected by the disease, highlighting the need for multidisciplinary management. Conclusion: Membranous glomerulopathy in women presents unique characteristics and clinical challenges, which demand special attention in diagnosis and treatment. Understanding the clinical repercussions and personalizing therapeutic approaches are essential to improve the quality of life of patients affected by this complex condition.

Animal models of membranous nephropathy: more choices and higher similarity.

Membranous nephropathy (MN) is an antibody-mediated autoimmune glomerular disease in which PLA2R1 is the main autoantibody. It has become the most common cause of adult nephrotic syndrome, and about one-third of patients can progress to end-stage kidney disease, but its pathogenesis is still unclear. Animal models can be used as suitable tools to study the pathogenesis and treatment of MN. The previous Heymann nephritis rat model and C-BSA animal model are widely used to study the pathogenesis of MN. However, the lack of target antigen expression in podocytes of model animals (especially rodents) restricts the application. In recent years, researchers constructed animal models of antigen-specific MN, such as THSD7A, PLA2R1, which more truly simulate the pathogenesis and pathological features of MN and provide more choices for the follow-up researchers. When selecting these MN models, we need to consider many aspects, including cost, difficulty of model preparation, labor force, and whether the final model can answer the research questions. This review is to comprehensively evaluate the mechanism, advantages and disadvantages and feasibility of existing animal models, and provide new reference for the pathogenesis and treatment of MN.

Kidney Outcomes in APOL1 High-Risk and Mendelian Variant in Patients with Adult Nephrotic Syndrome in Mass General Brigham Biobank

Kidney Outcomes in APOL1 High-Risk and Mendelian Variant in Patients with Adult Nephrotic Syndrome in Mass General Brigham Biobank

Different Dosage Regimens of Rituximab in Primary Membranous Nephropathy Treatment: A Systematic Review.

Primary membranous nephropathy (PMN) is one of the prevalent pathological types of adult primary nephrotic syndrome. Pathogenic autoantibodies targeting podocyte antigens such as phospholipase A2 receptor (PLA2R) lead to the disease. Patients frequently experience notable adverse effects when treated with conventional immunosuppressive therapies. Rituximab (RTX), a mouse/human monoclonal antibody, selectively depletes B cells and leads to a decrease in the antibody levels in the circulation, which helps to alleviate membranous nephropathy. Various RTX dosage regimens have been applied globally in the PMN treatment with satisfactory effects. Nevertheless, the optimal dosage of RTX has yet to be determined. This article reviews the application of different doses of RTX in the management of PMN so far.

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway.

Membranous nephropathy (MN) is a common pathological type of adult nephrotic syndrome. Up to 20% of patients with MN develop end-stage renal disease (ESRD). Podocytes have an important function in maintaining the glomerular filtration barrier and play a crucial role in the occurrence and development of proteinuria and MN. PI3K/AKT signaling pathway is involved in the entire process of podocyte growth, differentiation, and apoptosis. Kemeng Fang (KMF) is a traditional Chinese medicine formula that has been used to delay kidney injury. However, the therapeutic mechanism of KMF in MN is unclear. Here, the MN rat model was established by axillary, inguinal, and tail vein injections of cationized bovine serum albumin (C-BSA), and then KMF and PI3K inhibitor (LY294002) were administered. The data of liver function, kidney function, blood lipid, renal pathology, podocyte function, expression level of PI3K/AKT signaling pathway, and transcriptomics of rats demonstrated that KMF has a protective effect on the podocytes of MN rats by activating the PI3K/AKT signaling pathway, and it can effectively prevent the progression of MN.

Therapeutic targets in membranous nephropathy: plasma cells and complement.

Membranous nephropathy (MN) is an antibody-mediated autoimmune disease and the most common cause of nephrotic syndrome in adults. The discovery of phospholipase A2 receptor 1 (PLA2R1) as the first target antigen in patients with MN 15years ago has led to a paradigm shift in the pathobiological understanding of this disease. Autoantibodies against PLA2R1 as well as thrombospondin type-1 domain-containing 7A, the second identified antigen in adults, were shown to be disease-causing and act through local activation of the complement system, primarily via the classical and lectin pathways. These findings indicate that both plasma cells, the main source of antibodies and autoantibodies, as well as the complement system, the main pathogenic effector mechanism in MN, are rational and pathogenesis-based treatment targets in MN. This review summarizes pathomechanistic and clinical evidence for and against plasma cell- and complement-targeted treatments in MN.

Cyclophosphamide ameliorates membranous nephropathy by upregulating miR-223 expression, promoting M2 macrophage polarization and inhibiting inflammation.

Membranous nephropathy (MN), also known as membranous glomerulonephritis, is a leading cause of adult nephrotic syndrome. The main pathological features encompass the deposition of immune complexes within the glomerular basement membrane epithelial cells, thickening of the basement membrane, and fusion of the foot process. This study aims to investigate the role of the immune and inflammatory modulator miR-223 in the immunosuppressive and anti-inflammatory effects of cyclophosphamide (CTX) on membranous nephropathy (MN). miR-223 mimetics or inhibitors was used to regulate miR-223 levels. LPS induced inflammatory cell model and cell polarization. CTX was used to treat Lipopolysaccharides (LPS) induced inflammatory response and polarization. Cationic bovine serum albumin (c-BSA) induced BALB/c mouse MN model, while CTX was used to treat c-BSA induced MN. The miR-223 level in LPS induced inflammatory model cells was lower than that in control cells. The levels of inflammatory factors in LPS+miR-223 mimetics and CTX+miR-223i cells were lower than those in LPS and miR-223i cells. The protein levels of LPS+miR-223 mimic, CTX+miR-223i macrophage M2 phenotype markers Arginase-1 (Arg1), transforming growth factor β1 (TGF-β1), anti-inflammatory factors interleukin-4 (IL4) and interleukin-13 (IL13) were significantly higher than those of LPS and miR-223i. The effect of CTX was confirmed in a BALB/c mouse MN model induced by cationic bovine serum albumin (c-BSA). CTX upregulates the expression of miR-223, promotes polarization of M2 macrophages, alleviates the inflammatory response and renal injury of MN.

A review of progress on complement and primary membranous nephropathy.

Primary membranous nephropathy (PMN) is a predominant cause of adult nephrotic syndrome, with its incidence witnessing a progressive surge over time. Approximately 35% to 47% of patients progress to renal failure within 10 years, causing a huge social burden. Within China, the proportion of PMN in primary glomerular disease exhibits a gradual ascension. Recent studies have shown that the 3 activation pathways of complement: the classical pathway, mannose-binding lectin pathway, and alternative pathway, are all involved in the pathogenesis of PMN. Despite historical limitations in detecting C1q deposits on the glomeruli of PMN in the past, recent studies have confirmed the classical pathway is implicated in patients with PMN. Considering the dysregulation of the complement system has been observed in PMN, complement inhibitors become increasingly promising. Several clinical trials are presently underway to evaluate the efficacy of complement inhibitors, such as MASP2 antagonists (OMS721), C3 and C3b antagonists (APL2), FD inhibitors (BCX9930), C3aR antagonists (SB290157 and JR14a), FB inhibitors (LNP023). This article reviews the recent research progress on the role of the complement pathway in the pathogenesis of PMN, and underscores the importance of continued research into the complement pathway and its inhibitors, which may pave the way for groundbreaking advancements in the management of PMN.

Membranous nephropathy: pathogenesis and treatments.

Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one-third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end-stage renal disease within 10 years. The identification of phospholipase A2 receptor as the primary target antigen in MN has brought about a significant shift in disease management and monitoring. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression. By synthesizing the latest research findings and clinical insights, this review seeks to contribute to the ongoing efforts to enhance our understanding and management of this challenging autoimmune disorder.

Prognostic Impact of Proteinuria at Manifestation in Adult Nephrotic Syndrome Patients: Insights from a Prospective Cohort Study.

Background and objective Nephrotic syndrome is a significant worldwide health concern impacting millions of people and is marked by heavy proteinuria, edema, and decreased serum levels of albumin. Albuminuria arises from abnormal glomerular permeability and impaired tubular reabsorption, contributing to declining kidney function and a heightened risk of cardiovascular complications. The objective of this study was to investigate the prognostic role of proteinuria on the persistent decline in estimated glomerular filtration rate (eGFR) (<30 ml/minute/1.73m2) during follow-up and the dynamics of remission and relapse in various subtypes of nephrotic syndrome. Methods A total of 134 adult patients, diagnosed with various histopathological categories of nephrotic syndrome, were prospectively studied. Urine protein levels were assessed using the pyrogallol red-molybdate (PRM) method. The Kaplan-Meier analysis and log-rank test were utilized to assess the prognostic role of proteinuria at manifestation on persistent decline in estimated glomerular filtration rate(eGFR) (<30 ml/minute/1.73m2) and to evaluate remission and relapse based on proteinuria levels over an 18-month follow-up period. Results Patients with sub-nephrotic levels of proteinuria at manifestation did not progress to end-stage renal disease on follow-up. Patients with sub-nephrotic levels of albuminuria at manifestation were significantly associated with remission on follow-up. The Kaplan-Meier analysis indicated a significant probability of persistent eGFR decline (p < 0.001) in adult nephrotics with higher levels of albuminuria. Furthermore, patients with sub-nephrotic range proteinuria had earlier remission (p < 0.001) compared to those with relapse (p = 0.001) during the follow-up, as demonstrated by log-rank tests. Conclusion This study highlights that sub-nephrotic albuminuria at manifestation is linked to a reduced risk of renal progression and persistent eGFR decline compared to adult nephrotics with higher levels of albuminuria. Early detection and effective management of proteinuria, are crucial for preventing renal function decline and improving patient outcomes.

Spectrum of Glomerular Diseases in Biopsy Proven Nephrotic Syndrome in Adults in Tertiary Center of Nepal

Background: Glomerulonephritis (GN) is the important cause of chronic renal disease and had been reported as first common cause of CKD in Nepal after Diabetes and Hypertension. Correct diagnosis of glomerulonephritis requires renal biopsy and correlation with clinical and biochemical parameters. Methods: This was an observational study conducted in Department of Nephrology, Bir Hospital Kathmandu, during the period of one year. A total of 88 patients were enrolled. Nephrotic syndrome was established by a detailed history, physical examination and investigations including kidney biopsy.. Results: Among the enrolled patients.51.2% were male and 48.8% were female. Almost all patients had hyperlipidemia. IgA Nephropathy was found to be the first commonest cause in 22.8% , second Lupus Nephritis in 9.3%, third Focal Segmental Glomerulosclerosis (FSGS) in 18.2% fourth was Membranous Nephropathy (MN) in 13.6%, Minimal Change Disease (MCD) in 11.4%, 9.1% Diffuse Proliferative Glomerulonephritis (DPGN), 3.4%, Membranous Proliferative Glomerulonephritis (MPGN) in which one was HBsAg positive, 1.1% PSGN,and 1.1% C3 glomerulopathy. Hypertension (HTN) was found in 26%, renal impairment in 28%, hematuria in 16% anemia and oedema in 12%, and 30 % respectively. Conclusion: According to this study, IgA Nephropathy was the commonest cause 22.7% of Glomerulonephritis among total patients enrolled, whereas lupus nephritis was the second commonest 19.3% followed by focal segmental glomerulonephritis 18.1% and Membranous Nephropathy in 13.6%.

Immunohistochemical Analysis of Glomerular Phospholipase A2 Receptor in Primary and Secondary Membranous Glomerulonephritis

Background: A common cause of adult nephrotic syndrome (NS) is membranous glomerulonephritis (MGN). The larger portion of MGN in adults is the idiopathic/ primary MGN (iMGN). So many conditions like autoimmunity, malignant tumor, drugs and infections can cause a secondary form of MGN. We can diagnose primary/ idiopathic MGN after the omission of all known secondary causes. As we know M-type phospholipase A2 receptor (PLA2R) on podocytes is the target antigen in the pathogenesis of primary MGN. Phospholipase A2 receptor (PLA2R) can be detected by immunohistochemically. Differences between primary MGN (iMGN) and secondary MGN are essential because of treatment implications. Objective: To evaluate the histopathological pattern of MGN and to correlate with PLA2R deposition in primary and secondary MGN in a group of Bangladeshi people. Methods: The research method is descriptive cross- sectional and observational. The study population was 60 patients in the department of Histopathology, AFIP, Dhaka Cantonment, Dhaka for duration of six months period from January 2019 to June 2019. At first, adequate clinical information was taken and categorized as primary and secondary MGN on a clinical basis, thereafter immuno- histochemistry of anti-PLA2R was done from formalin-fixed paraffin block of those cases. Results: A total of 60 diagnosed cases of MGN, 56 patients were found primary, and 04 were secondary based on clinical data. In my study, all primary MGN was found as PLA2R positive. Conclusion: The present study exhibits that immuno- histochemistry with anti-PLA2R antibodies can be the best diagnostic method for diagnosis of idiopathic MGN which offers an opportunity for personalized medicine. JAFMC Bangladesh, Vol 19, No 2 (December) 2023: 24-28

Case Report: Mercury-induced renal autoimmunity – An insight into its pathogenesis

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. It may be idiopathic or due to secondary causes. Among the secondary causes, heavy metals like mercury are the one among others. Here is a male with nil comorbidities who, upon exposure to mercury-containing skin cream, developed proteinuria, which, on evaluation, was found to have dual renal lesions like membranous nephropathy and chronic interstitial nephritis. The uniform PLA2R staining within the glomerular capillary walls shows the ability of mercury to induce inflammation and autoimmunity. This case strengthens the findings of in vitro studies about mercury-induced inflammatory processes.

#2086 Understanding B cell memory autoreactivity in idiopathic membranous nephropathy for tailored therapy

Abstract Background and Aims Idiopathic membranous nephropathy (iMN) is an autoantibody-mediated glomerular disease, and one of the leading causes of nephrotic syndrome in adults. iMN is caused by the formation of immune complexes composed by IgG autoantibodies and target antigens expressed on podocytes. The main autoantigen is the phospholipase A2 receptor1 (PLA2R1) and the antibodies are mainly belonging to the IgG4 isotype. Those immune complexes are responsible for profound changes in the structure and function of the podocytes and disruption of the glomerular barrier. Nevertheless, despite complement components at the site of glomerular injury have been found in biopsies from patients with MN, many factors involved in the pathogenesis are still unclear. We overall aim at characterizing both the serological and the memory cellular component in iMN patients, with identification of dominant B cell epitopes recognized by circulating autoantibodies and autoreactive memory B cells, which could be potentially used to deplete PLA2R1 specific memory B cells and plasma blasts. Method We analyzed the serum from a cohort of 159 iMN patients collected at diagnosis without any previous or concomitant treatment as well as a similar number of healthy controls’ samples. An ELISA-based quantification method has been used to estimate the concentration of circulating anti-PLA2R1 antibodies. Furthermore, we processed 27 additional blood samples from independent iMN patients as well as age and gender matched healthy controls to extract and analyze peripheral blood mononuclear cells by flow cytometry (BD FACS Fortessa) and identify the major B and T cell populations via multi-color staining. In order to identify and clone human anti-PLA2R1 antibodies from primary memory B cells we reproduced the experimental workflow exactly as described in Lindner J.M. et al. Immunity 2019. The isolated antibodies were then characterized with analytical methods (affinity, binding, epitope determination and complement activation ability) and used in competition assays. Results A deep analysis of the serum reactivity has been performed and iMN patients showed a high prevalence of autoantibodies against PLA2R1, mostly of high affine IgG4 subclass with a broad concentration range (1-20ug/ml). A concomitant IgG1 response versus PLA2R1 has been also detected in the serum in different proportion with IgG4. An extended immunophenotyping of circulating peripheral blood mononuclear cells revealed an altered B and T cell compartment in iMN patients. In particular, we described an expansion of circulating CD27neg IgG4 memory B cells, IgG4 plasma blasts, CD4+ T follicular helper cells and CX3CR1+ T peripheral helper cells. Moreover, we isolated and cloned five very specific, highly affine, and somatically hypermutated patient's derived anti-PLA2R1 antibodies. Competition experiments between patient sera and patients’ derived monoclonal antibodies showed a strong inhibitory effect, indicating the presence of a shared epitope recognized on the surface of the CysR domain of PLA2R1. The identified epitope has also shown an important role in complement activation, despite a component patient-specific seems to be involved as well. Conclusion Overall, we performed a comprehensive characterization of the autoreactive B cell memory compartment in iMN, shedding lights on the complexity of the autoantibody repertoire. Indeed, the investigation of the granularity of the anti-PLA2R1 response in term of IgG1 versus IgG4 isotypes provided a potential new way to stratify the patients’ population and potentially tailored the therapy or follow the disease progression. Moreover, the isolation of patient's derived anti-PLA2R1 antibodies opened the possibility of using them the as tools to establish new models directly from the in vivo-selected specificities. Finally, the identification of an immunodominant epitope within PLA2R1 shared among the patients is crucial to develop molecules aimed at depletion of PLA2R1 specific memory B cells and plasma blasts in the patients.

#1360 SARS-COV-2 protein in renal tissue enhanced activation of complement system in MN patients with COVID-19 infection

Abstract Background and Aims Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Complement plays an important role in the pathogenesis of MN. COVID-19 infection has been reported to be associated with the occurrence and recurrence of MN. Only few kidney biopsies from COVID-19 patients demonstrate the presence of SARS-CoV-2 in the tissue. The clinical and pathological characteristics and complement system activation of patients with SARS-COV2 in renal tissue are unclear, needing to further study. Method From December 2022 to June 2023, patients with renal biopsy-proven MN at Beijing Anzhen hospital who had experienced COVID-19 infection before proteinuria onset and renal biopsy were enrolled. One hundred patients with primary MN diagnosed from December 2018 to June 2019 (with no COVID-19) were enrolled as control. Patient medical records were reviewed for clinical and pathological data. We performed immunofluorescence and in situ hybridization assays for detection of the SARS-COV2. Glomerular staining for factor H, FHR-5 and MAC were detected by immunohistochemical. Serum C5b-9 were detected by enzyme-linked immunosorbent assay. Clinicopathological and immunological features between MN patients with and without SARS-COV2 infection were analyzed. Results A total of 38 MN patients was proteinuria onset after COVID-19 infection, including 11 patients had SARS-COV protein positive staining along capillary loops in glomerular deposits or in cytoplasm of tubular epithelial cells. The immunofluorescence result shows strong colocalization of SARS-COV2 and IgG, which suggests that SARS-COV protein participated in the formation of immune complex. Compared with primary MN patients, the serum albumin level of 38 MN patients with COVID-19 infection were lower (p = 0.011). However, the clinical manifestations of 11 MN patients with SARS-COV2 renal positive staining were obviously serous. Compared with primary MN patients, urinary protein and serum creatine levels significantly increased (p = 0.027 and p = 0.005), while serum albumin levels decreased (p = 0.014) and the proportion of nephrotic syndrome (p = 0.037) was higher. There was no significant difference in pathological manifestations between MN patients with or without COVID-19 infection. In follow-up, the proportion of patients with urinary protein decreased greater than 50% in MN patients with COVID-19 infection was lower than that in primary MN patients. of urinary protein level Serum level of complement C3 (p = 0.007) and MAC (P = 0.001) in MN patients with COVID-19 infection was significantly higher than that of primary MN patients, especially MN patients with renal tissue positive staining of SARS-COV2 protein (p = 0.002 and p = 0.007). In 38 MN patients with COVID-19 infection, compared with patients with renal tissue negative for SARS-COV2 protein, patients with renal tissue positive for SARS-COV2 protein presented with stronger intensity of MAC deposition (p = 0.023) and factor H deposition (p = 0.002). Conclusion The clinical manifestation of MN patients who was onset after COVID-19 infection with renal tissue positive for SARS-COV2 protein were not only significantly worse than those of primary MN patients, but also worse than patients without tissue SARS-COV2 positive MN patients. We speculate that the reason is the enhanced activation of the complement system in renal tissue.

#340 Time dependent changes in the treatment of relapsing Minimal Change Disease – a multicenter cohort study

Abstract Background and Aims Prednisolone monotherapy is the most used initial immunosuppressive treatment for nephrotic syndrome in adults with Minimal Change Disease (MCD) but choice of treatment in relapsing MCD is not as well described. With the introduction of new drugs and increased concern relating to the adverse events of prednisolone, treatment might have changed over time. The aim of this study is to describe changes in daily clinical practice of relapsing MCD within the last 35 years. Method A multicenter, retrospective analysis of adult patients with biopsy proven MCD from 13 hospitals from 1987-2022 in Denmark and the Netherlands. Patients were identified from the pathology registers. Information on treatment and clinical outcomes was retrieved from health records. Relapse is defined when the nephrologist found indication to restart an immunosuppressive treatment or increase the ongoing immunosuppression in patients in partial or complete remission. Results We included 167 Dutch and 72 Danish patients (n = 239) with MCD. Most patients (n = 205, 86%) were initially treated with prednisolone monotherapy. Overall, 93% (n = 220) gained remission and 56% (n = 123) of those who went into remission had one or more relapse with 68% of these occurring in the first year after remission. At the time of relapse, 89% were in complete remission and 11% were in partial remission. At first relapse, prednisolone monotherapy was the most prescribed treatment both before and after 2010 (69% and 45%, respectively), while the use of CNI tripled after 2010 (p = 0.002) (10% to 32%). At second relapse, prescription of CNI after 2010 showed a five-fold increase compared with before 2010 (49% vs 10%, respectively) while the use of prednisolone monotherapy was halved (50% to 24%). The use of cyclophosphamide decreased by two-thirds (32% to 10%) after 2010. Before 2010, 54% of patients received prednisolone monotherapy for their third to 14th relapse, but after 2010 this decreased to 26%. The use of rituximab and CNI both increased and after 2010 these were both prescribed to about one third of patients at third to 14th relapse. The use of cyclophosphamide decreased from 30% to 2% comparing before and after 2010. Rituximab was only used after 2010, and more frequently with the number of relapses (6% at first relapse and 36% at third to 14th relapse). Regardless of the choice of treatment the rates of remission were high. Conclusion The treatment of relapses has changed over time with a reduced use of prednisolone monotherapy and cyclophosphamide and increased use of CNI and rituximab.

A Challenging Case of Primary Membranous Nephropathy with Renal Cell Carcinoma – Double Whammy

Membranous nephropathy is the most common cause of nephrotic syndrome in adults. It can be associated with malignancy especially in elderly patients, however; sometimes it is difficult to distinguish. Hereby we present an interesting case of primary membranous nephropathy in a patient with renal cell carcinoma.

Membranous nephropathy: genetics, antigens and antibodies

Membranous nephropathy is a kidney disorder characterized by thickening of the glomerular basement membrane, that causes nephrotic syndrome. It can be caused by various underlying conditions that result in damage to the filtering units of the kidneys, known as nephrons, producing massive proteinuria, hypoalbuminemia, edema and hyperlipidemia. Between 30 to 40% of cases of nephrotic syndrome in adults are due to membranous nephropathy. In recent decades, progress has been made with the discovery of antigens, antibodies and genes involved in the pathophysiology of the disease and a new classification system has been proposed. The presence of antigen-antibody complexes together with genetic factors may influence the susceptibility to such immune dysregulation, and states new information in a what was known between the etiologies of primary and secondary causes. The understanding of the antigens involved in membranous nephropathy is an area of active research, and additional antigens may be identified as our knowledge of the disease continues to evolve. This article summarizes some concepts and recent findings made on this topic.

Current status and prospects of genetic research on membranous nephropathy

Primary membranous nephropathy (PMN) is one of the most frequent pathological subtypes of nephrotic syndrome in adults. The use of genome-wide association study (GWAS) technology has propelled the transition from conventional medicine to precision medicine, offering a fresh perspective for comprehending the pathogenesis of PMN and individual variations in greater detail. Furthermore, GWAS will aid in clinical translation, laying a firm foundation for the precise diagnosis and treatment of PMN.

An Updated Review of Membranous Nephropathy.

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. The discovery of phospholipase A2 receptor (PLA2R) as a target antigen has led to a paradigm shift in the understanding and management of MN. At present, serum PLA2R antibodies are used for diagnosis, prognostication, and guiding treatment. Now, with the discovery of more than 20 novel target antigens, antigen mapping is almost complete. The clinical association of certain antigens provides clues for clinicians, such as the association of nerve epidermal growth factor-like 1 with malignancies and indigenous medicines. Serum antibodies are detected for most target antigens, except exostosin 1 and 2 and transforming growth factor-beta receptor 3, but their clinical utility is yet to be defined. Genome-wide association studies and studies investigating environmental factors, such as air pollution, shed more light on the underpinnings of MN. The standard therapy of MN diversified from cyclical cyclophosphamide and steroids to include rituximab and calcineurin inhibitors over the past decades. Here, we provide a cutting-edge review of MN, focusing on genetics, immune system and environmental factors, novel target antigens and their clinical characteristics, and currently available and emerging novel therapies in MN.