4.6 Review

Membranous nephropathy

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Review Pediatrics

Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA2R era

Luisa Safar-Boueri et al.

Summary: Membranous nephropathy (MN) is an immune complex-mediated cause of the nephrotic syndrome that can occur in all age groups, but is less common in children. While primary disease often requires immunosuppressive therapy, treatment for secondary forms of MN should target the underlying cause.

PEDIATRIC NEPHROLOGY (2021)

Article Hematology

Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial

Matthieu Mahevas et al.

Summary: The combination therapy of rituximab and belimumab shows promise in preventing the emergence of long-lived plasma cells in ITP patients, leading to increased overall response rates at 1 year. The safety and efficacy of this combination therapy appear high, with a decrease in circulating T-follicular helper cells observed.

HAEMATOLOGICA (2021)

Article Urology & Nephrology

Long-term renal survival and related risk factors for primary membranous nephropathy in Chinese children: a retrospective analysis of 217 cases

Ren Wang et al.

Summary: This study evaluated the long-term renal survival and related risk factors for primary membranous nephropathy (PMN) in children. The 5-year and 10-year cumulative renal survival rates of end-stage kidney disease (ESKD) in children with PMN were reported for the first time as 95.3% and 67.8%, respectively, and hypertension and proteinuria >= 50 mg/kg/day were found to be associated with renal outcome in children with PMN.

JOURNAL OF NEPHROLOGY (2021)

Article Urology & Nephrology

The clinicopathologic spectrum of segmental membranous glomerulopathy

Satoru Kudose et al.

Summary: Segmental membranous glomerulopathy (sMGN) is a rare PLA2R-negative variant of MGN with favorable prognosis, even in the absence of immunosuppressive treatment. During follow-up, most patients had stable/improved kidney function.

KIDNEY INTERNATIONAL (2021)

Article Urology & Nephrology

Successful treatment of PLA2R1-antibody positive membranous nephropathy with ocrelizumab

Tilman Schmidt et al.

Summary: Membranous nephropathy (MN) is commonly caused by antibodies targeting podocyte protein phospholipase A(2)receptor 1 (PLA(2)R1). While rituximab is often effective for treatment of MN, a significant portion of patients do not respond to it, necessitating the search for alternative treatment options. Ocrelizumab, a humanized B cell depleting antibody, may be an efficacious alternative treatment for patients with MN who fail to achieve remission or are immunologically sensitized to rituximab.

JOURNAL OF NEPHROLOGY (2021)

Article Urology & Nephrology

HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients

Lena Berchtold et al.

Summary: The study identified genetic variants in HLA-D and PLA2R1 genes associated with recurrence of primary membranous nephropathy. Specifically, donor expression of certain SNPs in these genes was predictive of recurrence, while recipient expression was not. A genetic risk score based on these SNPs can help identify patients at high risk of recurrence.

KIDNEY INTERNATIONAL (2021)

Article Urology & Nephrology

NELL1 is a target antigen in malignancy-associated membranous nephropathy

Tiffany N. Caza et al.

Summary: Patients with membranous nephropathy associated with malignancy were found to have unique NELL1 immune complexes in kidney biopsy tissue, with characteristic histopathology of incomplete capillary loop staining and IgG1 predominance. These NELL1-positive cases also showed a higher association with concurrent malignancy compared to other known types of membranous nephropathy.

KIDNEY INTERNATIONAL (2021)

Article Urology & Nephrology

Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis

Tiffany N. Caza et al.

Summary: Research has identified neural cell adhesion molecule 1 (NCAM1) as a target antigen in some cases of membranous lupus nephritis and rare cases of primary membranous nephropathy, colocalizing with IgG in glomerular immune deposits. Circulating antibodies to NCAM1 have been detected in serum of patients with NCAM1-associated membranous nephropathy, suggesting diagnostic significance. Future studies are needed to determine whether anti-NCAM1 antibody levels correlate with disease activity or response to therapy.

KIDNEY INTERNATIONAL (2021)

Review Urology & Nephrology

Membranous nephropathy: current understanding of various causes in light of new target antigens

Pierre Ronco et al.

Summary: Membranous nephropathy is an autoimmune disease caused by antibodies mostly directed to podocyte antigens. Recent advancements in technology have led to the discovery of new antigens and biomarkers associated with the disease, which may result in a new classification system based on serology and tissue antigen identification. The identification of these antigens also has significant implications for patient care, as they provide valuable markers for treatment monitoring and etiological investigations.

CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION (2021)

Article Urology & Nephrology

In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes

Aishwarya Ravindran et al.

Summary: In membranous lupus nephritis, EXT1/EXT2-positive patients have more favorable kidney biopsy findings with less chronicity, while EXT1/EXT2-negative patients are more likely to progress to ESKD. This suggests that the presence of EXT1/EXT2 is associated with better renal outcomes.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2021)

Review Urology & Nephrology

New 'Antigens' in Membranous Nephropathy

Sanjeev Sethi

Summary: Membranous nephropathy is a disease caused by immune complex deposition along the glomerular basement membrane, with PLA2R and THSD7A being the main antigens. New mass spectrometry techniques have led to the discovery of four novel types of MN, each with distinct clinical and pathologic features. Additional studies are needed to understand the pathophysiology, treatment response, and outcomes of these new MN subtypes.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2021)

Article Transplantation

Seropositive PLA2R-associated membranous nephropathy but biopsy-negative PLA2R staining

Jiao Luo et al.

Summary: This study identified a special form of PLA2R-associated MN, where patients had positive SAb but negative GAg, showing higher SAb levels, more severe clinicopathological manifestations, prominent chronic pathological lesions, and a higher likelihood of accompanying focal segmental glomerulosclerosis compared to their double-positive counterparts. IHC-P can be an alternative technique for revealing PLA2R glomerular deposits.

NEPHROLOGY DIALYSIS TRANSPLANTATION (2021)

Article Public, Environmental & Occupational Health

Workforce capacity for the care of patients with kidney failure across world countries and regions

Parnian Riaz et al.

Summary: The study showed that countries with different income levels generally have different numbers of healthcare workers. Nephrologists are the main physicians responsible for providing care to KF patients globally, but low-income countries reported shortages of various healthcare providers.

BMJ GLOBAL HEALTH (2021)

Article Medicine, Research & Experimental

Altered glycosylation of IgG4 promotes lectin complement pathway activation in anti-PL A2R1-associated membranous nephropathy

George Haddad et al.

Summary: In primary membranous nephropathy, anti-PLA2R1 IgG4 can induce podocyte injury by activating the lectin pathway. The study results indicate that aberrantly glycosylated IgG4 directly binds to mannose-binding lectin and induces proteolysis of synaptopodin and NEPH1 proteins through two distinct proteolytic pathways.

JOURNAL OF CLINICAL INVESTIGATION (2021)

Article Urology & Nephrology

Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney

Amin Abedini et al.

Summary: Microscopic analysis of urine sediment is commonly used in nephrology for diagnostic purposes. Single-cell transcriptomic analysis revealed that almost all kidney cell types can be identified in urine, with subject-specific and relatively stable cell-type composition. Urinary cells show similarities in gene expression with kidney and bladder cells.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2021)

Article Medicine, General & Internal

A Target Antigene-Based Approach to the Classification of Membranous Nephropathy

Shane A. Bobart et al.

Summary: This study described the clinical and pathological phenotype of membranous nephropathy associated with different target antigens. The distinction between primary and secondary MN was found to have limitations, and a refined terminology combining target antigen and associated disease was proposed for better classification.

MAYO CLINIC PROCEEDINGS (2021)

Review Medicine, General & Internal

Advances in Membranous Nephropathy

Pierre Ronco et al.

Summary: Recent advances in the treatment and pathophysiology of membranous nephropathy have shed light on the competition between traditional cyclophosphamide therapy and rituximab, with substantial progress made in the last two years. This has led to a more personalized approach to medicine in the diagnosis and treatment of the disease.

JOURNAL OF CLINICAL MEDICINE (2021)

Article Urology & Nephrology

Neural Epidermal Growth Factor-Like 1 Protein-Positive Membranous Nephropathy in Chinese Patients

Guoqin Wang et al.

Summary: The study found that about one third of Chinese patients with primary membranous nephropathy who were negative for PLA2R and THSD7A were positive for NELL-1. NELL-1-positive membranous nephropathy was more common than THSD7A-positive membranous nephropathy in patients who were negative for PLA2R.

CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2021)

Article Biochemistry & Molecular Biology

Altered Th17/Treg ratio as a possible mechanism in pathogenesis of idiopathic membranous nephropathy

Roza Motavalli et al.

Summary: In patients with IMN, the balance of Th17 and Treg cells in peripheral blood was disrupted, with increased expression of IL-21, IL-4, and IL-10, and decreased expression of FOXP3 and TGF-beta. Before treatment, alterations in the Th17/Treg lymphocyte ratio may play a role in the pathogenesis of IMN.

CYTOKINE (2021)

Article Urology & Nephrology

Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy

Laith Farah Al-Rabadi et al.

Summary: The study identified serine protease HTRA1 as a novel podocyte antigen in primary membranous nephropathy (MN) patients. Anti-HTRA1 antibodies in patients with HTRA1-associated MN were predominantly IgG4 and seemed to correlate with clinical disease activity. Screening of 118 quadruple-negative patients revealed a 4.2% prevalence of HTRA1-associated MN.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2021)

Article Urology & Nephrology

Protocadherin 7?Associated Membranous Nephropathy

Sanjeev Sethi et al.

Summary: Membranous nephropathy (MN) can be caused by antibodies targeting different antigens in the glomerular basement membrane (GBM), such as PLA2R, THSD7A, NELL1, SEMA3B, and now, the novel protein PCHD7. PCHD7 appears to define a distinct type of MN with specific characteristics in terms of staining pattern and antibody reactivity.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2021)

Review Urology & Nephrology

A conceptual framework linking immunology, pathology, and clinical features in primary membranous nephropathy

Gabriel B. Lerner et al.

Summary: Primary membranous nephropathy is a leading cause of adult nephrotic syndrome. The identification of PLA2R as a target antigen and the ability to measure circulating autoantibodies has provided new insights into the humoral aspect of the disease. Additionally, the detection and monitoring of autoantibody levels are crucial for guiding disease management.

KIDNEY INTERNATIONAL (2021)

Article Urology & Nephrology

The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy

Gema Fernandez-Juarez et al.

Summary: The study found that a cyclical corticosteroid-cyclophosphamide regimen was more effective in inducing persistent remission in patients with primary membranous nephropathy compared to sequential therapy with tacrolimus and rituximab, with a higher rate of complete remission. Overall, treatment with corticosteroid-cyclophosphamide resulted in a significantly greater number of patients achieving remission.

KIDNEY INTERNATIONAL (2021)

Article Urology & Nephrology

Anti-PLA2R1 Antibodies as Prognostic Biomarker in Membranous Nephropathy

Anne-Els Van de Logt et al.

Summary: This study found a clear association between baseline anti-PLA2R1 antibody titer and severity of nephrotic syndrome in membranous nephropathy patients, but this association was no longer significant when considering proteinuria and serum creatinine in the analysis. The relevance of a single measurement of anti-PLA2R1 antibodies at baseline as a prognostic biomarker in membranous nephropathy is questioned, suggesting the need for future studies on sequential measurements for disease progression prediction.

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Effect of belimumab on proteinuria and anti-phospholipase A2 receptor autoantibody in primary membranous nephropathy

Christine Barrett et al.

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A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathy mimics podocyte injury in patients

Catherine Meyer-Schwesinger et al.

KIDNEY INTERNATIONAL (2020)

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Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy

Sanjeev Sethi et al.

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Detection of PLA2R Autoantibodies before the Diagnosis of Membranous Nephropathy

Peter D. Burbelo et al.

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Clinical Relevance of Domain-Specific Phospholipase A2 Receptor 1 Antibody Levels in Patients with Membranous Nephropathy

Linda Reinhard et al.

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Adela Arapovic et al.

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Association of HLA Typing and Alloimmunity With Posttransplantation Membranous Nephropathy: A Multicenter Case Series

Ibrahim Batal et al.

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Simon A. Carter et al.

CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2020)

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Anan Chuasuwan et al.

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Longitudinal Changes in Health-Related Quality of Life in Primary Glomerular Disease: Results From the CureGN Study

Shannon L. Murphy et al.

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Proteomic Analysis of Complement Proteins in Membranous Nephropathy

Aishwarya Ravindran et al.

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Membranous Nephropathy Associated With Indigenous Indian Medications Containing Heavy Metals

M. Naveen Kumar et al.

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Elizabeth K. Neumann et al.

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Emilio D. Poggio et al.

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Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis

Richard Furie et al.

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Multi-Autoantibody Signature and Clinical Outcome in Membranous Nephropathy

Gian Marco Ghiggeri et al.

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Gabriella Moroni et al.

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Ofatumumab for multirelapsing membranous nephropathy complicated by rituximab-induced serum-sickness

Manuel Alfredo Podesta et al.

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Rituximab in Patients With Phospholipase A2 Receptor-Associated Membranous Nephropathy and Severe CKD

Nicolas Hanset et al.

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Ragnar Palsson et al.

KIDNEY INTERNATIONAL REPORTS (2020)

Article Urology & Nephrology

Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies

Shane A. Bobart et al.

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Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy

Christelle Zaghrini et al.

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Pietro A. Canetta et al.

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The bias between different albumin assays may affect clinical decision-making

Anne-Els van de Logt et al.

KIDNEY INTERNATIONAL (2019)

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Exostosin 1/Exostosin 2-Associated Membranous Nephropathy

Sanjeev Sethi et al.

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Jihwan Park et al.

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Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy

F. C. Fervenza et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

Article Urology & Nephrology

Treatment of Membranous Nephropathy in Patients With THSD7A Antibodies Using Immunoadsorption

Julia Weinmann-Menke et al.

AMERICAN JOURNAL OF KIDNEY DISEASES (2019)

Review Immunology

Complement Inhibitors in Clinical Trials for Glomerular Diseases

Peter F. Zipfel et al.

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Recurrent venous thromboembolism in primary membranous nephropathy despite direct Xa inhibitor therapy

Monica L. Reynolds et al.

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Nephrotic Syndrome: Oedema Formation and Its Treatment With Diuretics

Sanjana Gupta et al.

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Duodenal Schwannoma as a Rare Association With Membranous Nephropathy: A Case Report

Zao Zhang et al.

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Treatment Patterns Among Adults and Children With Membranous Nephropathy in the Cure Glomerulonephropathy Network (CureGN)

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KIDNEY INTERNATIONAL REPORTS (2019)

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Phospholipase A2 Receptor 1 Epitope Spreading at Baseline Predicts Reduced Likelihood of Remission of Membranous Nephropathy

Barbara Seitz-Polski et al.

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Dyslipidaemia in nephrotic syndrome: mechanisms and treatment

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Glomerular mannose-binding lectin deposition in intrinsic antigen-related membranous nephropathy

Norifumi Hayashi et al.

NEPHROLOGY DIALYSIS TRANSPLANTATION (2018)

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The Most N-Terminal Region of THSD7A Is the Predominant Target for Autoimmunity in THSD7A-Associated Membranous Nephropathy

Larissa Seifert et al.

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Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy

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