 |
GN in TenA bite-size podcast brought to you by the International Society of Glomerular Disease. Author: International Society of Glomerular Disease
A bite-size podcast brought to you by the International Society of Glomerular Disease. Nephrologists and glomerular disease experts Dr. Kenar Jhaveri (Northwell Health/Hofstra University) and Dr. Koyal Jain (UNC Chapel Hill) take a lighthearted look at the latest research, discuss clinical practice, and interview leaders in glomerular medicine all in a short enough time to listen on your coffee break. Language: en Genres: Health & Fitness, Life Sciences, Medicine, Science Contact email: Get it Feed URL: Get it iTunes ID: Get it Trailer: |
Listen Now...
Episode 11: Nephmadness Special! Matt Sparks and Aarushi Varshney on C3G
Episode 11
Wednesday, 11 March, 2026
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, Lectin, and Alternative).3. Safety & MonitoringVaccination: Because these drugs inhibit the complement cascade, patients MUST be vaccinated against Neisseria meningitidis and Streptococcus pneumoniae at least two weeks before starting therapy.Prophylaxis: If urgent treatment is required, patients should start prophylactic antibiotics (such as Penicillin, Augmentin, or Ciprofloxacin).Resources & Studies MentionedNephMadness: The annual educational "tournament" in nephrology that inspired this discussion.The APPEAR Trial (Iptacopan): Investigated the efficacy of the oral factor B inhibitor in patients with C3G.The VALIANT Trial (Pegcetacoplan): Evaluated the C3 inhibitor in patients with C3G and primary immune complex MPGN, including post-transplant patients.The hosts and guests of this GN in 10 episode do not have any disclosures to make relevant to the content of this episode.
