Long-term Outcome of Adult Patients With Membranous Nephropathy Treated With Rituximab.

Introduction: Rituximab (RTX) therapy has become the standard of care for treatment of membranous nephropathy (MN). However, data on hard outcomes such as end-stage kidney disease (ESKD) and loss of estimated glomerular filtration rate (eGFR), are lacking.

Methods: This was a retrospective study on all patients with MN treated with RTX between January 2000 and December 2022.

Monoclonal Gammopathy in ANCA-Negative Pauci-immune Crescentic Glomerulonephritis: Is There an Association?

Background: In a small subset of patients with pauci-immune crescentic glomerulonephritis (PICGN), antinuclear cytoplasmic antibodies (ANCA) are not identified, and patients are referred to as having 'ANCA-negative' vasculitis. The cause of the disease in this subset of patients has remained elusive. We explored the role of monoclonal gammopathy (MG) in those with ANCA-negative PICGN.

Antigens in membranous nephropathy: discovery and clinical implications.

Membranous nephropathy is an autoimmune disease that results in an accumulation of antigen-antibody (IgG) immune complexes along the subepithelial region of the glomerular basement membrane and is the most common cause of nephrotic syndrome in adults. The diagnosis of membranous nephropathy is based on the presence of granular IgG on immunofluorescence microscopy and subepithelial electron dense deposits along the glomerular basement membrane on electron microscopy. Prior to 2009, the target antigen within the immune complexes was unknown.

The Clinicopathologic Characteristics of Recurrent Lupus Nephritis Post-Transplant Using Surveillance and Indication Biopsies.

Introduction: The incidence of recurrent lupus nephritis (RLN) after kidney transplantation (KTx) varies with higher rates of RLN reported in surveillance biopsy-based studies (vs. clinically indicated biopsies).

Methods: We present a multisite retrospective study evaluating surveillance and clinically indicated biopsies in 209 first KTx recipients who had native lupus disease.

Sex-specific clinical presentations and outcomes in ANCA vasculitis presenting with severe kidney disease.

Background: The impact of sex in the clinical presentation and outcomes of patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) has not been studied, particularly in patients with severe kidney involvement at presentation (eGFR < 15 mL/min/1.73m2).

Methods: A retrospective cohort study on MPO- or PR3-ANCA positive patients with AAV (MPA or GPA) and eGFR<15 ml/min/1.

The importance of identifying new and putative target antigens associated with membranous nephropathy: evidence from a Sardinian cohort.

Background: Membranous nephropathy (MN) is a leading cause of nephrotic syndrome (NS). Since the identification of anti-phospholipase A2 receptor (anti-PLA2R) antibodies in 2009, the use of laser microdissection and tandem mass spectrometry (LMD/MS) has allowed the discovery of several target antigens in MN.

Methods: In this retrospective cohort study, adult patients evaluated at the Division of Nephrology at Brotzu Hospital (Cagliari, Italy) with biopsy-proven MN and a negative serological test for anti-PLA2R antibody underwent LMD/MS, performed at the Department of Laboratory Medicine and Pathology of Mayo Clinic (Rochester, MN, USA).

Clinical Phenotypes and Renal Outcomes in PLA2R-Associated Membranous Nephropathy: A Multi-Center Cohort Study with Unsupervised Cluster Analysis.

Background: Membranous nephropathy (MN) associated with phospholipase A2 receptor (PLA2R) antibodies is the most common cause of nephrotic syndrome in non-diabetic adult patients. This study investigated the relationship between clinical phenotypes and renal outcomes in this population, emphasizing the potential for phenotype-based treatment stratification.

Methods: We conducted a retrospective, multi-center cohort study of PLA2R-positive MN.

Phospholipase A2 receptor-positive membranous nephropathy detected by laser microdissection and mass spectrometry in patients negative by immunofluorescence for phospholipase A2 receptor on kidney biopsy.

Introduction: Membranous nephropathy (MN) is characterized by subepithelial deposition of immune complexes along the glomerular basement membrane. The muscle-type phospholipase A2 receptor (PLA2R) has been identified as the principal antigen in MN, and its detection via immunofluorescence (IF) studies remains a diagnostic cornerstone. Advancements, including laser microdissection/mass spectrometry (LMD/MS), offer enhanced sensitivity for antigen identification, independent of epitope accessibility.

The Mayo MGRS Prediction Tool calculates the risk of finding monoclonal gammopathy of renal significance in a kidney biopsy in patients with monoclonal gammopathy.

Introduction: Monoclonal gammopathy of renal significance (MGRS) is increasingly recognized as an important cause of kidney failure. A kidney biopsy remains an important diagnostic measure. However, a kidney biopsy is not without risks.

Predicting Remission in Antiphospholipase A2 Receptor Antibody-Associated Membranous Nephropathy: A Secondary Analysis of the GEMRITUX, MENTOR, and STARMEN Trials.

Key Points: In phospholipase A2 receptor-membranous nephropathy, clinical variables and antibody levels over 3 or 6 months of treatment were predictors of remission at 1 year. Prediction models at 3 and 6 months had similar performance predicting remission, with the 3-month model allowing for earlier assessment of response. The 3-month and 6-month prediction models could be applied in those treated with supportive therapy, rituximab, calcineurin inhibitors, or cyclophosphamide.

Lupus nephritis: redefining the treatment goals.

The course of proliferative lupus nephritis is characterized by flares of activity alternating with periods of quiescence against a background of chronic immune dysregulation. An accurate assessment of disease activity is of unassailable importance to tailor therapy. In the present communication, we discuss the available clinical, serologic, and histologic tools to evaluate disease activity and how they may be applied to redefine the treatment goals in lupus nephritis.

Updated diagnostic and therapeutic management for membranous nephropathy.

Purpose Of Review: Pioneering contributions in membranous nephropathy over the last decade have greatly enhanced our comprehension of its pathogenesis, diagnosis, and treatments, igniting renewed interest in this entity. This review provides an updated perspective on the diagnosis and therapeutic management of membranous nephropathy.

Recent Findings: The identification of antiphospholipase A2 receptor (PLA2R) antibodies in 50-80% of membranous nephropathy patients was a key breakthrough.

Antimalarials in Lupus Nephritis: How Strong Is the Evidence?

SLE is a chronic multisystem autoimmune disease that affects the kidneys in approximately 50% of patients, with the prevalence rising to as high as 70% in certain populations, such as African American and Asian people. Antimalarials-and particularly hydroxychloroquine (HCQ)-are currently considered a mainstay of therapy, together with immunosuppressants. Over the past decades, several studies have extensively investigated the mechanisms of action of antimalarial agents and their potential beneficial properties in patients with SLE in general.

A reliable clinical test for detection of membranous nephropathy antigens using laser microdissection and mass spectrometry.

Membranous nephropathy (MN) results from accumulation of antigen-antibody immune complexes along the subepithelial region of the glomerular basement membranes. Over the last years, 13 target antigens have been discovered and include PLA2R, THSD7A, EXT1 and EXT2, NELL1, SEMA3B, NCAM1, CNTN1, HTRA1, FAT1, PCDH7, NTNG1, PCSK6 and NDNF, accounting for 80-90% of MN antigens. MN associated with many of these antigens have distinctive clinicopathologic findings.

Treatment of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Diffuse Alveolar Hemorrhage With Avacopan.

Objective: Avacopan, an activated complement factor 5 receptor antagonist, has been approved as adjunct therapy for severe active antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Current evidence supports the management of AAV presenting with diffuse alveolar hemorrhage (DAH) by administering glucocorticoids combined with either rituximab or cyclophosphamide in addition to supportive care. The role of avacopan in patients with DAH as a primary severe disease manifestation of AAV has not been well established.

Granulomatosis with polyangiitis with and without antineutrophil cytoplasmic antibodies: a case-control study.

Objective: ANCA-negative granulomatosis with polyangiitis (GPA) remains a diagnosis of exclusion. Clinical differences between patients with ANCA-negative vs ANCA-positive GPA have not been analysed in sizable case-control studies, and the effects of ANCA-seroconversion from negative to positive are not well documented.

Methods: A single-centre, sex and age matched case-control study evaluated ANCA-negative vs ANCA-positive GPA from 1 January 1996 to 31 December 2015.

Diagnostic yield of exome and genome sequencing after non-diagnostic multi-gene panels in patients with single-system diseases.

Background: Though next-generation sequencing (NGS) tests like exome sequencing (ES), genome sequencing (GS), and panels derived from exome and genome data (EGBP) are effective for rare diseases, the ideal diagnostic approach is debated. Limited research has explored reanalyzing raw ES and GS data post-negative EGBP results for diagnostics.

Results: We analyzed complete ES/GS raw sequencing data from Mayo Clinic's Program for Rare and Undiagnosed Diseases (PRaUD) patients to assess whether supplementary findings could augment diagnostic yield.