{"type":"rich","version":"1.0","provider_name":"Transistor","provider_url":"https://transistor.fm","author_name":"GN in Ten","title":"Episode 11: Nephmadness Special! Matt Sparks and Aarushi Varshney on C3G","html":"","width":"100%","height":180,"duration":1409,"description":"In this episode, hosts Dr. Kenar Jhaveri and Dr. Koyal Jain are joined by Dr. Matt Sparks (co-creator of NephMadness) and Dr. Aarushi Varshney to discuss the evolving landscape of C3 Glomerulopathy (C3G). The conversation highlights the shift from traditional electron microscopy-based classifications to modern immunofluorescence-based diagnosis, as well as the groundbreaking arrival of two new FDA-approved targeted therapies.The NephMadness MatchupThis episode focuses on the C3G bracket pitting two critical aspects of C3G against each other:Team Diagnosis: Focusing on the challenges of distinguishing C3G from infection-related GN or monoclonal gammopathy.Team Treatment: Highlighting the new era of factor B and C3 inhibitors that are revolutionizing patient outcomes.Key Takeaways1. Challenges in DiagnosisThe \"Two Orders of Magnitude\" Rule: Modern diagnosis is based on immunofluorescence (IF) showing C3 deposition that is at least two orders of magnitude greater than any other immunoglobulin.C3G vs. PIGN: It can be difficult to distinguish C3G from Post-Infectious Glomerulonephritis (PIGN). Clinical clues include patient age, the persistence of low C3 levels after infection resolution, and the presence (or absence) of sub-epithelial humps on pathology.The Role of Monoclonal Gammopathy: In older patients, it is critical to rule out monoclonal gammopathy (using SPEP and free light chain assays) as a driver of complement activation.2. The New Therapeutic EraThe panel discussed two landmark drugs that have recently shifted the C3G treatment paradigm:Iptacopan: An oral factor B inhibitor that showed a 30% reduction in proteinuria at six months in the APPEAR trial.Pegcetacoplan: A subcutaneous infusion (twice weekly) C3 inhibitor that demonstrated a nearly 70% reduction in proteinuria and stabilization of eGFR in the VALIANT trial.A \"Hammer\" Approach: Pegcetacoplan is described as a \"larger hammer\" because it acts at the crux of all three complement pathways (Classical,...","thumbnail_url":"https://img.transistorcdn.com/kA5i5pDNY48C1bT4aTakysX4M1kpvKsFppYIkQ0Hgfo/rs:fill:0:0:1/w:400/h:400/q:60/mb:500000/aHR0cHM6Ly9pbWct/dXBsb2FkLXByb2R1/Y3Rpb24udHJhbnNp/c3Rvci5mbS9zaG93/LzQ0NjQyLzE2OTM2/ODM5MzItYXJ0d29y/ay5qcGc.webp","thumbnail_width":300,"thumbnail_height":300}