Membranous glomerulonephritis

Adult Onset ◽

Common Cause ◽

End Stage Renal Failure ◽

Surface Molecules ◽

Secondary Membranous Nephropathy ◽

End Stage

Membranous glomerulonephritis (MGN) is the most common cause of adult-onset nephrotic syndrome, and a common glomerular cause of end-stage renal failure. It is caused by antibodies to podocyte surface molecules, usually autoantibodies. In most patients with primary membranous nephropathy the target is the phospholipase A2 receptor. It is hoped that robust assays for this antibody will help to guide therapy but it has not been possible to test this adequately yet. Primary MGN accounts for about 70% of cases with regional variations. MGN is more common in men than women (approximately 2:1) and its peak incidence is in middle adult life. Secondary membranous nephropathy occurs in lupus and some other immune or autoimmune disorders, in hepatitis B infection, after exposure to some drugs or toxins, and in some cancers.

Case Review of lgG4-Related Disease Patient with Combined Tubulointerstitial Nephritis and Membranous Nephropathy Coexisting with Cholangiocarcinoma: Case Report

Journal of the Medical Association of Thailand ◽

10.35755/jmedassocthai.2020.11.10685 ◽

2020 ◽

Vol 103 (11) ◽

pp. 1230-1235

Keyword(s):

Renal Failure ◽

Membranous Nephropathy ◽

Tubulointerstitial Nephritis ◽

Disease Patient ◽

Case Review ◽

Related Disease ◽

Wide Range ◽

Serum Igg4 ◽

Secondary Membranous Nephropathy

Immunoglobulin G4-related disease (IgG4-RD) has recently been recognized as an autoimmune disorder involving multiple organs. The kidney is a represented organ with a wide range of renal manifestations. The authors report a case of an 83-year-old Thai male with combined IgG4 tubulointerstitial nephritis and membranous nephropathy coexisting with cholangiocarcinoma. The patient presented with proteinuria, acute renal failure, eosinophilia, hypocomplementemia, and high serum IgG4 concentration. The diagnosis was IgG 4-related tubulointerstitial nephritis and membranous nephropathy on renal biopsy, with negative immunohistochemistry for anti-phospholipase A2 receptor antibodies. Magnetic resonance imaging (MRI) abdomen showed two wedge shaped arterial enhancing lesions of liver. Liver biopsy revealed adenocarcinoma, compatible with cholangiocarcinoma. Proteinuria and renal failure were resolved with initial steroid treatment. Meanwhile, IgG4-related membranous nephropathy should be considered in the differential diagnosis for patients with proteinuria. Potentially, IgG4-RD may be rarely associated with carcinoma development. However, further studies are recommended to ratify and confirm the association between IgG4-RD and incidence of malignancies. Keywords: IgG4-related disease, Membranous nephropathy, Secondary membranous nephropathy, Tubulointerstitial nephritis, Cholangiocarcinoma

Mechanisms of Primary Membranous Nephropathy

Biomolecules ◽

10.3390/biom11040513 ◽

2021 ◽

Vol 11 (4) ◽

pp. 513

Author(s):

Yan Gu ◽

Hui Xu ◽

Damu Tang

Keyword(s):

Membranous Nephropathy ◽

Full Spectrum ◽

The Past ◽

Kidney Glomerulus ◽

Recent Developments ◽

One Step ◽

Stage Renal Disease ◽

End Stage ◽

Antibody Levels

Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus and one of the leading causes of nephrotic syndrome. The disease exhibits heterogenous outcomes with approximately 30% of cases progressing to end-stage renal disease. The clinical management of MN has steadily advanced owing to the identification of autoantibodies to the phospholipase A2 receptor (PLA2R) in 2009 and thrombospondin domain-containing 7A (THSD7A) in 2014 on the podocyte surface. Approximately 50–80% and 3–5% of primary MN (PMN) cases are associated with either anti-PLA2R or anti-THSD7A antibodies, respectively. The presence of these autoantibodies is used for MN diagnosis; antibody levels correlate with disease severity and possess significant biomarker values in monitoring disease progression and treatment response. Importantly, both autoantibodies are causative to MN. Additionally, evidence is emerging that NELL-1 is associated with 5–10% of PMN cases that are PLA2R- and THSD7A-negative, which moves us one step closer to mapping out the full spectrum of PMN antigens. Recent developments suggest exostosin 1 (EXT1), EXT2, NELL-1, and contactin 1 (CNTN1) are associated with MN. Genetic factors and other mechanisms are in place to regulate these factors and may contribute to MN pathogenesis. This review will discuss recent developments over the past 5 years.

IMMUNODIAGNOSIS IN MEMBRANOUS NEPHROPATHY

Wiadomości Lekarskie ◽

10.36740/wlek202009110 ◽

2020 ◽

Vol 73 (9) ◽

pp. 1861-1866

Author(s):

Magdalena Ratajczak ◽

Ewa Poleszak ◽

Tomasz Chrościcki

Keyword(s):

Membranous Nephropathy ◽

Antinuclear Antibodies ◽

Aim Analysis ◽

Non Invasive ◽

Secondary Form ◽

Stage Renal Disease ◽

End Stage ◽

Receptor Antibodies ◽

Primary Form

One of the diseases leading to chronic end-stage renal disease is membranous nephropathy (MN). The main cause of this disease is the formation of antibodies to foreign and native antigens. Membranous nephropathy can be conventionally divided into 2 types: primary form (when the primary disease is unknown) and secondary form. Detection of appropriate antibodies is one of the methods to recognize and differentiate primary and secondary forms. A large role in non-invasive diagnosis of MN and differentiation of the primary form from the secondary play antinuclear antibodies (ANA), antibodies against granulocyte cytoplasm (ANCA), antiglomerular basement antibodies (anti-GBM) and phospholipase A2 receptor antibodies (anti-PLA2R). Differentiation matters when choosing a treatment choice. In the primary form, it is immunosuppression, and in the form of secondary treatment, it consists in curing or controlling diseases that can cause symptoms of MN. The aim: Analysis of serological methods helpful in immunodiagnosis of membranous nephropathy.

Glomerular Diseases Associated with Malignancies: Histopathological Pattern and Association with Circulating Autoantibodies

Antibodies ◽

10.3390/antib9020018 ◽

2020 ◽

Vol 9 (2) ◽

pp. 18

Author(s):

Sophia Lionaki ◽

Smaragdi Marinaki ◽

Konstantinos Panagiotellis ◽

Ioanna Tsoumbou ◽

George Liapis ◽

...

Keyword(s):

Membranous Nephropathy ◽

Kidney Biopsy ◽

Rapidly Progressive Glomerulonephritis ◽

Glomerular Diseases ◽

Transmembrane Glycoprotein ◽

Nephritic Syndrome ◽

Acute Nephritic Syndrome ◽

Circulating Autoantibodies ◽

End Stage

Aim: Glomerular diseases (GD) associated with malignancies (AM, GDAM) have unique features, which are important to recognize, in the light of the progress made in cancer therapy. We aimed to describe the clinical and histopathological characteristics of patients with GDAM in relation to the presence of circulating autoantibodies, pointing to potential immune pathogenic pathways connecting cancer to GD. Materials and Methods: The included patients were studied retrospectively on the basis of a kidney biopsy proving GD and a related biopsy to establish the diagnosis of AM. We recorded patients’ demographics, serological and laboratory parameters, histopathological findings, and the type of malignancy, GD, and therapy. Results: In total, 41 patients with GDAM, with a mean age of 63.1 (±10.7) years, were studied. In 28 (68.3%) cases, GD was associated with a solid tumor, and in 13 (31.7%) patients with a lymphoid malignancy. The most frequent histopathological pattern was membranous nephropathy (43.9%). Overall, at the time of GD diagnosis, 17% of the patients were positive for antinuclear antibodies (ANA), and 12.2% for antineutrophil cytoplasmic autoantibodies (ANCA), all against myeloperoxidase (MPO). In addition, 93.3% of the patients who had membranous nephropathy were negative for transmembrane glycoprotein M-type phospholipase A2 receptor (PLA2R) antibody. Sixteen patients (39.0%) presented with acute nephritic syndrome, of whom five (31.25%) developed rapidly progressive glomerulonephritis. In a mean follow-up time of 36.1 (±28.3) months, nine (21.95%) patients ended up with end-stage kidney disease, and eight (19.5%) died. Conclusion: We found that 3.2% of patients who underwent a native kidney biopsy in our institution during the past decade, for any reason, were identified as having some type of GD associated with a malignancy. Serology indicated a significant presence of ANA or MPO-ANCA antibodies in patients with nephritic syndrome and the absence of PLA2R antibodies in patients with membranous nephropathy.

Membranous glomerulonephritis

10.1093/med/9780199592548.003.0061_update_001 ◽

2018 ◽

Author(s):

Daniel C. Cattran ◽

Heather N. Reich

Keyword(s):

Nephrotic Syndrome ◽

Hepatitis B ◽

Renal Biopsy ◽

Clinical Picture ◽

Membranous Nephropathy ◽

Hepatitis B Infection ◽

Immunoglobulin G4 ◽

Secondary Membranous Nephropathy ◽

Secondary Causes

Membranous glomerulonephritis (MGN) usually presents as nephrotic syndrome, which may be severe. It is primarily a disease of adults, men more than women, with a peak incidence in the fourth and fifth decades. It is hoped that proven tests for the characteristic anti-PLA2R antibodies of primary MGN may become established, but the diagnosis currently rests on renal biopsy showing characteristic subepithelial granular immune deposits. These usually contain immunoglobulin G4 and complement. Other patterns may suggest secondary causes of MGN. Secondary membranous nephropathy occurs in lupus and some other immune or autoimmune disorders, in hepatitis B infection, after exposure to some drugs or toxins, and in some cancers. Secondary causes are more common at extremes of age, and are often made obvious by the history or clinical picture. How hard to look for malignancy is controversial, but malignancy is much more likely in patients over 60 years, and may be apparent at presentation.

Membranous nephropathy in patients with HIV: a report of 11 cases

BMC Nephrology ◽

10.1186/s12882-020-02042-x ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Vivek Charu ◽

Nicole Andeen ◽

Vighnesh Walavalkar ◽

Jessica Lapasia ◽

Jin-Yon Kim ◽

...

Keyword(s):

Membranous Nephropathy ◽

Viral Loads ◽

Immunodeficiency Virus ◽

Antibody Titers ◽

Stage Renal Disease ◽

End Stage ◽

Nephrotic Range Proteinuria ◽

Tissue Reactivity

Abstract Background Membranous nephropathy (MN) has been recognized to occur in patients with human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. The prevalence of phospholipase A2 receptor (PLA2R)-associated MN in this group has not been well studied. Methods We conducted a retrospective review of electronic pathology databases at three institutions to identify patients with MN and known HIV at the time of renal biopsy. Patients with comorbidities and coinfections known to be independently associated with MN were excluded. Results We identified 11 HIV-positive patients with biopsy-confirmed MN meeting inclusion and exclusion criteria. Patient ages ranged from 39 to 66 years old, and 10 of 11 patients (91%) were male. The majority of patients presented with nephrotic-range proteinuria, were on anti-retroviral therapy at the time of biopsy and had low or undetectable HIV viral loads. Biopsies from 5 of 10 (50%) patients demonstrated capillary wall staining for PLA2R. Measurement of serum anti-PLA2R antibodies was performed in three patients, one of whom had positive anti-PLA2R antibody titers. Follow-up data was available on 10 of 11 patients (median length of follow-up: 44 months; range: 4–145 months). All patients were maintained on anti-retroviral therapy (ARV) and 5 patients (52%) received concomitant immunosuppressive regimens. Three patients developed end-stage renal disease (ESRD) during the follow-up period. Conclusions MN in the setting of HIV is often identified in the setting of an undetectable viral loads, and similar to other chronic viral infection-associated MNs, ~ 50% of cases demonstrate tissue reactivity with PLA2R antigen, which may be seen without corresponding anti-PLA2R serum antibodies.

Serum Antibody and Glomerular Antigen of Antiphospholipase A2 Receptor in Chinese Patients with Idiopathic Membranous Nephropathy

BioMed Research International ◽

10.1155/2020/1693710 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Qiu-hua Zhang ◽

Mian Wu ◽

Zhi-gang Hu ◽

Xiao-bin Liu ◽

Biao Huang ◽

...

Keyword(s):

Renal Function ◽

Serum Creatinine ◽

Serum Albumin ◽

Membranous Nephropathy ◽

Serum Antibody ◽

Chinese Patients ◽

Idiopathic Membranous Nephropathy ◽

Secondary Membranous Nephropathy ◽

Clinical Correlations

Background. M-type phospholipase A2 receptor (PLA2R) is the first autoantigen responsible for idiopathic membranous nephropathy (IMN). However, serum PLA2R antibody (PLA2R-Ab) can be inaccurate in distinguishing between IMN and secondary membranous nephropathy, while renal PLA2R antigen (PLA2R-Ag) emerges as an ancillary diagnostic. The present study is aimed at examining the associations between PLA2R-Ab in sera and PLA2R-Ag in kidneys in IMN patients. Methods. A total of 93 patients with IMN were retrospectively identified. Their serum PLA2R-Ab and renal PLA2R-Ag expression levels were determined, and the clinical correlations between these parameters and clinical features were examined. Results. The sensitivities of serum PLA2R-Ab and renal PLA2R-Ag for diagnosing IMN were 74.2% and 88.2%, respectively (P<0.001), with poor consistency. Higher serum PLA2R-Ab levels were correlated to stronger renal PLA2R-Ag expression (P=0.048). Patients with positive PLA2R-Ab significantly differed from those with negative levels, in terms of proteinuric levels over 24 hours (4.54 vs. 3.46 g/day, P=0.015) and serum albumin (23.28 vs. 27.95 g/L, P=0.038). Among patients with positive renal PLA2R-Ag, patients with positive PLA2R-Ab had significantly higher 24-hour proteinuria, when compared to patients with negative PLA2R-Ab (4.57 vs. 3.08 g/day, P=0.005). Among those with positive PLA2R-Ab in sera, their PLA2R-Ab levels were correlated with the estimated glomerular filtration and serum creatinine. Conclusion. Serum PLA2R-Ab exhibits a closer correlation with proteinuric severity and renal function, when compared to renal PLA2R-Ag.

Successful foetal outcome in a patient with primary membranous nephropathy and circulating anti-phospholipid antibodies: A case report

10.33118/oaj.rep.2019.01.002 ◽

2018 ◽

Keyword(s):

Nephrotic Syndrome ◽

Phospholipase A2 ◽

Membranous Nephropathy ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Foetal Outcome ◽

Circulating Autoantibodies ◽

Patient’S History

There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), especially those with circulating autoantibodies to M-type phospholipase A2 receptor (PLA2R), the major autoantigen in primary MN. Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space, frequently associated with circulating M-type phospholipase A2 receptor. Nephrotic syndrome (massive proteinuria and hypoalbuminemia) at diagnosis predicts poor prognosis. Pregnancy with active MGN is high risk for foetal loss, intrauterine growth restriction, and pre-eclampsia, and may worsen maternal renal function, especially with the presence of antiphospholipid antibody syndrome (APLA). We report a 23-year-old gravida in her first pregnancy, suffering from MGN and severe nephrotic syndrome, complicated by APLA syndrome. The patient was treated with enoxaparin, aspirin azathioprine, and Prednisone for a short time, in addition to furosemide and albumin intravenously. She was delivered at 30 weeks due to deteriorating maternal and foetal conditions. A successful neonatal and maternal outcome was achieved in this case. The patient's history revealed thrombocytopenia and APLA syndrome and continues to be treated chronically with enoxaparin. Kidney biopsy performed after delivery showed membranous MGN stage II-III. Herein, we present a case of successful pregnancy and foetal outcome in a young woman with APLA syndrome and MN. Keywords: Membranous GN, Nephrotic Syndrome, Anti-Phospholipid Antibodies.

An Overview of Molecular Mechanism of Nephrotic Syndrome

International Journal of Nephrology ◽

10.1155/2012/937623 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 15

Author(s):

Juliana Reis Machado ◽

Laura Penna Rocha ◽

Precil Diego Miranda de Menezes Neves ◽

Eliângela de Castro Cobô ◽

Marcos Vinícius Silva ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Membranous Nephropathy ◽

Epithelial Mesenchymal Transition ◽

Membrane Damage ◽

Basal Membrane ◽

Experimental Models ◽

Mesenchymal Transition ◽

Disease Occurrence ◽

Phospholipase A2 Receptor

Podocytopathies (minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS)) together with membranous nephropathy are the main causes of nephrotic syndrome. Some changes on the expression of nephrin, podocin, TGF-β, and slit diaphragm components as well as transcription factors and transmembrane proteins have been demonstrated in podocytopathies. Considering the pathogenesis of proteinuria, some elucidations have been directed towards the involvement of epithelial-mesenchymal transition. Moreover, the usefulness of some markers such as TGF-β1, nephrin, synaptopodin, dystroglycans, and malondialdehyde have been determined in the differentiation between MCD and FSGS. Experimental models and human samples indicated an essential role of autoantibodies in membranous glomerulonephritis, kidney damage, and proteinuria events. Megalin and phospholipase-A2-receptor have been described as antigens responsible for the formation of the subepithelial immune complexes and renal disease occurrence. In addition, the complement system seems to play a key role in basal membrane damage and in the development of proteinuria in membranous nephropathy. This paper focuses on the common molecular changes involved in the development of nephrotic proteinuria.

The Prevalence of Mesangial Electron-Dense Deposits in PLA2R-Positive Membranous Nephropathy

Nephron ◽

10.1159/000519912 ◽

2021 ◽

pp. 1-5

Author(s):

Gabriel Giannini ◽

Lois J. Arend

Keyword(s):

Electron Microscopy ◽

Nephrotic Syndrome ◽

Membranous Nephropathy ◽

Immunofluorescence Microscopy ◽

Common Cause ◽

Electron Dense Deposit ◽

Dense Deposit ◽

Dense Deposits ◽

Negative Biopsies

Introduction: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults and can be primary or secondary. The antigenic target of antibodies in 70% of primary cases is phospholipase A2 receptor (PLA2R). The presence or absence of mesangial electron-dense deposits has been used to distinguish between primary and secondary MN. Mesangial deposits suggest MN due to lupus, infection, or other causes, though they are reported to occur in approximately 10% of primary MN. Staining for PLA2R is now frequently used for confirming a diagnosis of primary MN. If mesangial deposits predict a secondary cause, they should be more frequent in PLA2R-negative biopsies. Methods: A review of institutional kidney biopsies between March 2017 and June 2020 identified all cases of MN. Cases with a diagnosis of lupus or near “full-house” staining by immunofluorescence microscopy (IF) were excluded. Light microscopy, IF, and electron microscopy (EM) were performed. PLA2R staining was performed by IF. EM for all cases was reviewed and electron-dense deposit location, distribution, and size were determined. Results: Ninety-three cases of MN were identified, of which 86 had both PLA2R staining and EM performed. Of these, 51 cases (59%) were positive for PLA2R and 35 (41%) were negative. Mesangial electron-dense deposits were present in 22 (25.6%) of the 86 cases, including 27.5% (14/51) of PLA2R-positive cases and 22.8% (8/35) of PLA2R-negative cases. No difference was seen in size or distribution of deposits, or other features considered suggestive of secondary MN. Conclusion: PLA2R-negative cases were not more likely to have mesangial deposits than PLA2R-positive cases. Mesangial deposits should not be used as an indicator of secondary MN.