Anti Phospholipase A2 Receptor 1 Antibodies and Membranous Nephropathy Recurrence After Kidney Transplantation.

Introduction: Membranous nephropathy can lead to end-stage kidney disease, for which kidney transplantation is the preferred therapy. However, the disease often relapses, which can impact allograft survival.

Methods: We conducted a prospective multicenter study in France involving 72 patients with membranous nephropathy who were awaiting and then underwent kidney transplantation.

Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody-Positive Primary Membranous Nephropathy.

Introduction: Primary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN.

Methods: Patients with newly diagnosed or relapsed PMN (cohort 1 [C1];  = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2];  = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up.

Ectodomain shedding of PLA2R1 is mediated by the metalloproteases ADAM10 and ADAM17.

Phospholipase A2 receptor 1 (PLA2R1) is a 180-kDa transmembrane protein that plays a role in inflammation and cancer and is the major autoantigen in membranous nephropathy, a rare but severe autoimmune kidney disease. A soluble form of PLA2R1 has been detected in mouse and human serum. It is likely produced by proteolytic shedding of membrane-bound PLA2R1 but the mechanism is unknown.

Autoantibodies Targeting Nephrin in Podocytopathies.

Background: Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear.

Methods: We conducted a multicenter study to analyze antinephrin autoantibodies in adults with glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, antineutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis, as well as in children with idiopathic nephrotic syndrome and in controls.

Electrifying Friedel-Crafts Intramolecular Alkylation toward 1,1-Disubstituted Tetrahydronaphthalenes.

In this work, we successfully employed electrochemical conditions to promote a Hofer-Moest, intramolecular Friedel-Crafts alkylation sequence. The reaction proceeds under mild conditions, employing carboxylic acids as starting materials. Notably, the electrochemical process performed in batch was adapted to a continuous flow electrolysis apparatus to provide a significant improvement.

Mayo Clinic Consensus Report on Membranous Nephropathy: Proposal for a Novel Classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

A child with semaphorin 3b-associated membranous nephropathy effectively treated with obinutuzumab after rituximab resistance.

Background: Membranous nephropathy is a glomerular disease characterized by the presence of immune-complexes deposited in the subepithelial space of the glomerular basement membrane. It is the main cause of nephrotic syndrome in adults, while in children it is very infrequent. Anti-CD20 monoclonal antibodies, mainly rituximab, represent a specific treatment for this disease.

Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome.

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown.

Proprotein convertase subtilisin/kexin type 6 (PCSK6) is a likely antigenic target in membranous nephropathy and nonsteroidal anti-inflammatory drug use.

Drugs are an important secondary cause of membranous nephropathy (MN) with the most common drugs associated with MN being nonsteroidal anti-inflammatory drugs (NSAIDs). Since the target antigen in NSAID-associated MN is not known, we performed laser microdissection of glomeruli followed by mass spectrometry (MS/MS) in 250 cases of PLA2R-negative MN to identify novel antigenic targets. This was followed by immunohistochemistry to localize the target antigen along the glomerular basement membrane and western blot analyses of eluates of frozen biopsy tissue to detect binding of IgG to the novel antigenic target.

Network-Based Assessment of Minimal Change Disease Identifies Glomerular Response to IL-7 and IL-12 Pathways Activation as Innovative Treatment Target.

Minimal change disease (MCD), a major cause of nephrotic syndrome, is usually treated by corticosteroid administration. MCD unresponsiveness to therapy and recurrences are nonetheless frequently observed, particularly in adults. To explore MCD-related pathogenetic mechanisms and to identify novel drug targets ultimately contributing to novel therapeutic avenues with a certain specificity for MCD, we compared glomerular transcriptomes from MCD with membranous nephropathy (MN) patients and healthy controls.

Glomerular diseases in pregnancy: pragmatic recommendations for clinical management.

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage.

Predictive Models for Recurrent Membranous Nephropathy After Kidney Transplantation.

Unlabelled: Recurrent membranous nephropathy (MN) posttransplantation affects 35% to 50% of kidney transplant recipients (KTRs) and accounts for 50% allograft loss 5 y after diagnosis. Predictive factors for recurrent MN may include HLA-D risk alleles, but other factors have not been explored with certainty.

Methods: The Australian and New Zealand Dialysis and Transplant registry was used to develop 3 prediction models for recurrent MN (Group Least Absolute Shrinkage and Selection Operator [LASSO], penalized Cox regression, and random forest), which were tuned using tenfold cross-validation in a derivation cohort with complete HLA data.

Incremental and Personalized Hemodialysis Start: A New Standard of Care.

Introduction: Incremental hemodialysis (iHD) may attenuate "dialysis shock" and reduce costs, preserving quality of life. It is considered difficult to reconcile with HD wards' routine; fear of underdialysis and increasing mortality are additional concerns. The aim of this study was to evaluate mortality, morbidity, and costs in a large HD ward where iHD is the standard of HD start.