scholarly journals Primary membranous glomerulonephritis with negative serum PLA2R in haemophilia A successfully managed with rituximab – case report and review of the literature

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nicholas Meyer ◽  
Wendy Cooper ◽  
Paul Kirwan ◽  
Roger Garsia ◽  
Scott Dunkley ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Treatment Strategies ◽  
Membranous Glomerulonephritis ◽  
Sudden Onset ◽  
Haemophilia A ◽  
Electron Microscopic ◽  
Hiv Coinfection ◽  
Phospholipase A2 Receptor ◽  
Wide Range

Abstract Background Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause a wide range of glomerular pathologies. In people with haemophilia, transfusion-associated infections with these viruses are common and definitive pathological diagnosis in this population is complicated by the difficulty of safely obtaining a renal biopsy. Membranous nephropathy (MN) is a common cause of adult onset nephrotic syndrome occurring in both primary and secondary forms. Primary MN is associated with podocyte autoantibodies, predominantly against phospholipase A2 receptor (PLA2R). Secondary disease is often associated with viral infection; however, infrequently with HIV or HCV. Distinguishing these entities from each other and other viral glomerular disease is vital as treatment strategies are disparate. Case presentation We present the case of a 48-year-old man with moderate haemophilia A and well-controlled transfusion-associated HCV and HIV coinfection who presented with sudden onset nephrotic range proteinuria. Renal biopsy demonstrated grade two membranous nephropathy with associated negative serum PLA2R testing. Light and electron microscopic appearances were indeterminant of a primary or secondary cause. Given his extremely stable co-morbidities, treatment with rituximab and subsequent angiotensin receptor blockade was initiated for suspected primary MN and the patient had sustained resolution in proteinuria over the following 18 months. Subsequent testing demonstrated PLA2R positive glomerular immunohistochemistry despite multiple negative serum results. Conclusions Pursuing histological diagnosis is important in complex cases of MN as the treatment strategies between primary and secondary vary significantly. Serum PLA2R testing alone may be insufficient in the presence of multiple potential causes of secondary MN.

scholarly journals Development and validation of a discrimination model between primary PLA2R-negative membranous nephropathy and minimal change disease confirmed by renal biopsy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Wu ◽  
Yiding Zhang ◽  
Wen Cui ◽  
Yijun Dong ◽  
Yingyang Geng ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Treatment Strategies ◽  
Test Group ◽  
Minimal Change ◽  
Specific Marker ◽  
Discrimination Ability ◽  
Discrimination Model ◽  
Phospholipase A2 Receptor

AbstractMembranous nephropathy (MN) and minimal change disease (MCD) are two common causes leading to nephrotic syndrome (NS). They have similar clinical features but different treatment strategies and prognoses. M-type phospholipase A2 receptor (PLA2R) is considered as a specific marker of membranous nephropathy. However, its sensitivity is only about 70%. Therefore, there is a lack of effective and noninvasive tools to distinguish PLA2R-negative MN and MCD patients without renal biopsy. A total 949 patients who were pathologically diagnosed as idiopathic MN or MCD were enrolled in this study, including 805 idiopathic MN and 144 MCD. Based on the basic information and laboratory examination of 200 PLA2R-negative MN and 144 MCD, we used a univariate and multivariate logistic regression to select the relevant variables and develop a discrimination model. A novel model including age, albumin, urea, high density lipoprotein, C3 levels and red blood cell count was established for PLA2R-negative MN and MCD. The discrimination model has great differential capability (with an AUC of 0.904 in training group and an AUC of 0.886 in test group) and calibration capability. When testing in all 949 patients, our model also showed good discrimination ability for all idiopathic MN and MCD.

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

2020 ◽  
Vol 103 (11) ◽  
pp. 1230-1235
Keyword(s):  
Renal Failure ◽  
Membranous Nephropathy ◽  
Tubulointerstitial Nephritis ◽  
Disease Patient ◽  
Case Review ◽  
Related Disease ◽  
Phospholipase A2 Receptor ◽  
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

scholarly journals Development and Validation of a Discrimination Model Between Primary PLA2R-Negative Membranous Nephropathy and Minimal Change Disease Confirmed by Renal Biopsy

2020 ◽  
Author(s):  
Feng Wu ◽  
Yiding Zhang ◽  
Wen Cui ◽  
Yijun Dong ◽  
Yingyang Geng ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Multivariate Logistic Regression Analysis ◽  
Test Group ◽  
Minimal Change ◽  
Clinical Feature ◽  
Specific Marker ◽  
Discrimination Model ◽  
Phospholipase A2 Receptor

Abstract BackgroundMembranous nephropathy (MN) and minimal change disease (MCD) are two common causes leading to nephrotic syndrome (NS). They have similar clinical feature but different treatment strategy and prognosis. M-type phospholipase A2 receptor (PLA2R) is considered as a specific marker of membranous nephropathy. However, its sensitivity is only about 70%. Therefore, there is a lack of effective and noninvasive tools to distinguish PLA2R-negative MN and MCD patients without renal biopsy. We aim to develop a discrimination model using noninvasive parameters for distinguishing the two diseases and support immediate treatment before result of renal biopsy.MethodsA total 949 patients who were pathologically diagnosed as idiopathic MN or primary MCD in the First Affiliated Hospital of Zhengzhou University from January 2017 to August 2019 were enrolled in this study, including 805 idiopathic MN (605 PLAR2-positive MN and 200 PLA2R-negative MN) and 144 primary MCD. Based on the basic information and laboratory examination of 200 PLA2R-negative MN and 144 MCD, we used univariate and multivariate logistic regression analysis to select the relevant variables and develop the discrimination model. ROC curves and calibration curves were used to evaluate the diagnostic ability and calibration ability of the model. The decision curve was used to show the net benefit. We also tested the effectiveness of our model in all 949 patients.ResultsA novel model that included age, albumin, urea, high density lipoprotein, urea and red blood cell count was established for PLA2R-negative MN and MCD. The discrimination model has good differential capability (an AUC of 0.889 in training group and an AUC of 0.920 in test group) and calibration capability. When testing in all 949 patients, our model also showed good discrimination ability for all idiopathic MN and MCD.ConclusionWe constructed a discrimination model with high diagnostic effectiveness for PLA2R-negative MN and MCD. The model could also be used for all idiopathic MN and MCD patients.

Membranous glomerulonephritis

2018 ◽  
Author(s):  
Daniel C. Cattran ◽  
Heather N. Reich
Keyword(s):  
Nephrotic Syndrome ◽  
Hepatitis B ◽  
Renal Biopsy ◽  
Clinical Picture ◽  
Membranous Nephropathy ◽  
Membranous Glomerulonephritis ◽  
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 glomerulonephritis

2018 ◽  
Author(s):  
Daniel C. Cattran ◽  
Heather N. Reich
Keyword(s):  
Membranous Nephropathy ◽  
Adult Life ◽  
Membranous Glomerulonephritis ◽  
Adult Onset ◽  
Common Cause ◽  
End Stage Renal Failure ◽  
Surface Molecules ◽  
Phospholipase A2 Receptor ◽  
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.

scholarly journals M-Type Phospholipase A2 Receptor Staining in Children with Idiopathic Membranous Nephropathy: PLA2R Staining in Children with IMN

2019 ◽  
Vol 12 (1) ◽  
pp. 27-32
Author(s):  
Yosuke Inaguma ◽  
Atsutoshi Shiratori ◽  
Taku Nakagawa ◽  
Kyoko Kanda ◽  
Makiko Yoshida ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Renal Biopsy ◽  
Clinical Data ◽  
Membranous Nephropathy ◽  
Pediatric Patients ◽  
Idiopathic Membranous Nephropathy ◽  
Target Antigen ◽  
Positive Staining ◽  
Phospholipase A2 Receptor

Background: Membranous Nephropathy (MN) is a common cause of nephrotic syndrome in adults that can also occur in children, albeit less frequently. Recently, the M-type phospholipase A2 receptor (PLA2R) was identified as the target antigen in idiopathic membranous nephropathy (IMN), making it a useful marker for diagnosis. However, there are few studies describing the potential role of PLA2R in children with IMN. The aim of this study was to clarify the involvement of PLA2R in childhood IMN. Methods: We enrolled 11 patients diagnosed with IMN from January 1998 to March 2017. We performed PLA2R staining in paraffin-embedded renal biopsy sections. The clinical data were collected from the patients’ medical records. Results: The median age at biopsy was 6 years (range, 4 to 14 years). A single 6-year-old boy among all pediatric patients with IMN had granular PLA2R staining along his glomerular capillary loops and the prevalence of PLA2R-positivity was 9%. He also showed IgG4 co-dominant staining in terms of IgG subclass. There were no apparent differences in his clinical features such as clinical data at the time of renal biopsy, the time from the treatment initiation to remission, and relapse or renal dysfunction during the follow-up period. Conclusion: We suggest that PLA2R staining can be a diagnostic tool for patients with IMN of any age, though pediatric patients with IMN have lower prevalence of PLA2R-positive staining than adult patients.

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

2018 ◽  
Keyword(s):  
Nephrotic Syndrome ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Membranous Glomerulonephritis ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Phospholipase A2 Receptor ◽  
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.

scholarly journals An Overview of Molecular Mechanism of Nephrotic Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
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 ◽  
Membranous Glomerulonephritis ◽  
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.

scholarly journals Analysis of Glomerular IgG Subclasses Switch in Idiopathic Membranous Nephropathy Classified by Glomerular Phospholipase A2 Receptor Antigen and Serum Antibody

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Hao-yuan Cui ◽  
Chao Li ◽  
Hang Li ◽  
Yu-bing Wen ◽  
Lin Duan ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Serum Antibody ◽  
Chinese Patients ◽  
Idiopathic Membranous Nephropathy ◽  
Igg Subclass ◽  
Electron Microscopic ◽  
Phospholipase A2 Receptor ◽  
Stage 1

Background. The role of IgG subclass in idiopathic membranous nephropathy (IMN) was unclarified. Recent study found IgG subtype switches from IgG1 to IgG4 in the early pathological stage in IMN. The profile of IgG subclass in phospholipase A2 receptor- (PLA2R-) related and PLA2R-unrelated IMN was unrevealed. Our study is aimed at testifying whether IgG subclass switch existed in PLA2R-related and PLA2R-unrelated IMN, respectively. Methods. Our study retrospectively enrolled 157 Chinese patients with biopsy-confirmed IMN between September 2017 and November 2019. We measured glomerular PLA2R antigen and serum anti-PLA2R antibody to classify the patients into PLA2R-related ( n = 132 ) and PLA2R-unrelated ( n = 25 ) subgroup. We evaluated glomerular IgG subclass by immunofluorescence (IF) predominance. Our study defined IgG subclass deposition as predominant if the IF score was higher than the other three and ≥1 +, or as codominant if the IF intensity was equal to any other and ≥1 +. We explored the relationship between IF predominance of glomerular IgG subtype and electron microscopic (EM) stages of IMN. Results. We did not find statistical difference of predominant or codominant rate (pre/co-rate) among EM stages in any subclass ( P > 0.05 ). Pre/co-rate of IgG3 linearly associated with EM stage in total and PLA2R-related subgroup ( P = 0.044 , P = 0.013 ). PLA2R-related subgroup showed higher IgG4 intensity ( 2.1 ± 0.6 vs. 1.6 ± 0.7 , P = 0.001 ) and pre/co-rate of IgG4 in stage 1 (97% vs. 57%, P = 0.015 ) than PLA2R-unrelated group. We found no difference of IgG subclass pre/co-rate in different EM stages or linear association between pre/co-rate of IgG1, IgG2, IgG4, and EM stages ( P > 0.05 ). Conclusions. Pre/co-rate of IgG3 declined with EM stage in total and PLA2R-related subgroup. We did not find IgG subclass switches from IgG1 to IgG4 in either IMN patients or subgroups.

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