GN in Ten

International Society of Glomerular Disease
  • 5.0 (4)
  • MEDICINE
  • UPDATED MONTHLY

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.

  1. Episode 12: NephMadness Special! IgAN (Again?!): New B-Cell Targets vs. Complement Inhibitors

    20H AGO

    Episode 12: NephMadness Special! IgAN (Again?!): New B-Cell Targets vs. Complement Inhibitors

    It’s the "New England Journal of IgA" these days, and we’re just living in it! In this special NephMadness edition of GN in Ten, hosts Dr. Kenar Jhaveri and Dr. Koyal Jain are joined by NephMadness co-creator Dr. Matt Sparks and Duke Fellow Dr. Ale Tomasi to break down the heavy hitters in the IgA Nephropathy bracket. Matt’s dog also joins us for a special, possibly biased cameo. We’re moving past "ACE first, think later" and diving into the upstream battle: B-cell modulators (BAFF/APRIL inhibitors) versus Complement inhibitors. Whether you’re team "Hit Zero" or team "Alternative Pathway," this episode covers the latest trial data from ORIGIN, VISIONARY, and APPLAUSE to help you fill out your bracket.  The "Hit Zero" Hypothesis While we all know the classic four-hit hypothesis of IgAN, new therapies are targeting even further upstream—what some are calling "Hit Zero."  Pathophysiology Recap: IgAN starts with galactose-deficient IgA1 (Hit 1), leading to autoantibody production (Hit 2), immune complex formation (Hit 3), and mesangial deposition/damage (Hit 4). B-Cell Modulators: These drugs target BAFF (B-cell activating factor) and/or APRIL (a proliferation-inducing ligand) to reduce the production of those pesky autoantibodies right at the source.  The B-Cell Contenders: Sibeprenlimab & Atacicept Sibeprenlimab ("Sibi"): A monoclonal antibody directed at APRIL. The Data: Showed a 50% reduction in proteinuria at interim analysis and a nearly 98% reduction in APRIL levels. Status: Currently has conditional FDA approval. Atacicept: A fusion protein that dual-blocks both BAFF and APRIL. The Data (ORIGIN trials): Demonstrated a 45.7% proteinuria reduction at 36 weeks and, notably, stabilization of eGFR slope in long-term follow-up. Pronunciation Debate: Is it "Attack-a-cept" or "A-tassi-cept"? The investigators say "Attack," because it’s out for blood.  The Complement Contender: Iptacopan Mechanism: A factor B inhibitor that specifically targets the alternative complement pathway, which is increasingly recognized as a key driver of IgAN damage. The APPLAUSE Study: This oral, twice-daily pill showed a 38% reduction in proteinuria at nine months. Safety First: Because complement blockade increases the risk of infections from encapsulated bacteria, patients must be up to date with vaccinations for meningitis, streptococcal and pneumococcal infections.  The Verdict: Who Wins the Bracket? Tune in to find out what our experts think… then fill out your own bracket! References Atacicept Lafayette R, Barbour SJ, Brenner RM, Campbell KN, Doan T, Eren N, Floege J, Jha V, Kim BS, Liew A, Maes B, Pal A, Pecoits-Filho R, Phoon RKS, Rizk DV, Suzuki H, Tesař V, Trimarchi H, Wei X, Zhang H, Barratt J; ORIGIN Phase 3 Trial Investigators. A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy. N Engl J Med. 2026 Feb 12;394(7):647-657. doi: 10.1056/NEJMoa2510198. Epub 2025 Nov 6. PMID: 41196369. Lafayette R, Barbour S, Israni R, Wei X, Eren N, Floege J, Jha V, Kim SG, Maes B, Phoon RKS, Singh H, Tesař V, Lin CJF, Barratt J. A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy. Kidney Int. 2024 Jun;105(6):1306-1315. doi: 10.1016/j.kint.2024.03.012. Epub 2024 Mar 27. PMID: 38552841. Sibeprenlimab Perkovic V, Trimarchi H, Tesar V, Lafayette R, Wong MG, Barratt J, Suzuki Y, Liew A, Zhang H, Carroll K, Jha V, Quevedo A, Han SH, Praga M, Chacko B, Sahay M, Cheung CK, Kooienga L, Walsh M, Xia J, Fajardo C, Shah L, Hafkin J, Rizk DV; VISIONARY Trial Investigators Group. Sibeprenlimab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial. N Engl J Med. 2026 Feb 12;394(7):635-646. doi: 10.1056/NEJMoa2512133. Epub 2025 Nov 8. PMID: 41211929. Mathur M, Barratt J, Chacko B, Chan TM, Kooienga L, Oh KH, Sahay M, Suzuki Y, Wong MG, Yarbrough J, Xia J, Pereira BJG; ENVISION Trial Investigators Group. A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy. N Engl J Med. 2024 Jan 4;390(1):20-31. doi: 10.1056/NEJMoa2305635. Epub 2023 Nov 2. PMID: 37916620; PMCID: PMC7615905. Iptacopan Perkovic V, Barratt J, Rovin B, Kashihara N, Maes B, Zhang H, Trimarchi H, Kollins D, Papachristofi O, Jacinto-Sanders S, Merkel T, Guerard N, Renfurm R, Hach T, Rizk DV; APPLAUSE-IgAN Investigators. Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy. N Engl J Med. 2025 Feb 6;392(6):531-543. doi: 10.1056/NEJMoa2410316. Epub 2024 Oct 25. PMID: 39453772. Zhang H, Rizk DV, Perkovic V, Maes B, Kashihara N, Rovin B, Trimarchi H, Sprangers B, Meier M, Kollins D, Papachristofi O, Milojevic J, Junge G, Nidamarthy PK, Charney A, Barratt J. Results of a randomized double-blind placebo-controlled Phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy. Kidney Int. 2024 Jan;105(1):189-199. doi: 10.1016/j.kint.2023.09.027. Epub 2023 Oct 31. PMID: 37914086.  The hosts and guests of this GN in 10 episode do not have any disclosures to make relevant to the content of this episode.

    21 min
  2. Episode 11: Nephmadness Special! Matt Sparks and Aarushi Varshney on C3G

    20H AGO

    Episode 11: Nephmadness Special! Matt Sparks and Aarushi Varshney on C3G

    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 Matchup This 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 Takeaways 1. Challenges in Diagnosis The "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 Era The 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 & Monitoring Vaccination: 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 Mentioned NephMadness: 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.

    23 min
  3. Board Review Basics #4: ANCA Vasculitis

    FEB 4 · BONUS

    Board Review Basics #4: ANCA Vasculitis

    In this episode of GN in Ten, hosts Dr. Kenar Jhaveri and Dr. Koyal Jain break down the essential "must-knows" for ANCA-associated vasculitis (AAV). Geared toward board preparation and clinical practice, this bite-sized session covers everything from the initial diagnosis and the role of kidney biopsy to the latest advancements in induction and maintenance therapy. Key Discussion Points Diagnosis & Biopsy Strategy: Why checking specific MPO and PR3 titers is more reliable than general C/P-ANCA. The hosts also discuss the value of biopsy in older patients to assess chronicity and guide treatment duration.Induction Therapy: Comparing the "three pillars" of induction: Rituximab, Cyclophosphamide (IV vs. oral), and the increasingly popular combination therapy for organ-threatening disease.The Steroid Taper: A shift toward "less is more." Following the PEXIVAS protocol, the hosts explain how to aggressively taper steroids to minimize toxicity, especially when using adjunctive therapies.Plasma Exchange (PLEX): Does it still have a role? A nuanced look at the PEXIVAS trial results and why PLEX is now largely reserved for severe pulmonary hemorrhage or rapidly worsening AKI.Avacopan (C5a Receptor Inhibitor): Insights from the ADVOCATE trial on how this steroid-sparing agent is changing the landscape of AAV treatment.Maintenance: Long-term strategies using Rituximab (typically up to 18 months) or Azathioprine, and when to consider switching agents for refractory cases. Essential Reading & Resources To master ANCA vasculitis, the hosts recommend reviewing these landmark studies: PEXIVAS: Plasma Exchange and Glucocorticoids in ANCA-Associated Vasculitis — Evaluated PLEX and reduced-dose steroids.ADVOCATE: Avacopan for the Treatment of ANCA-Associated Vasculitis — The landmark trial for C5a receptor inhibition.RAVE: Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis — Established rituximab as a standard for induction.MAINRITSAN: Rituximab versus Azathioprine for Maintenance in ANCA-Associated Vasculitis — Compared maintenance strategies.RITUXVAS: Rituximab versus Cyclophosphamide in ANCA-Associated Renal Vasculitis — Induction in patients with severe renal involvement.RITAZAREM: Rituximab as Maintenance Therapy in Relapsing ANCA-Associated Vasculitis — Focus on maintenance for relapsing disease.

    21 min
  4. Episode 10: Louise Oni and Jun Oh

    12/27/2025

    Episode 10: Louise Oni and Jun Oh

    In this episode of GN in Ten, hosted by Dr. Kenar Jhaveri and Dr. Koyal Jain, takes a deep dive into the specialized world of pediatric glomerular disease. Joining the show are world-renowned pediatric nephrologists Dr. Louise Oni (Great Ormond Street Hospital, London) and Dr. Jun Oh (University of Hamburg, Germany) to discuss the "pediatric lag" in drug development and the massive global efforts currently underway to bring targeted therapies to children. Key Highlights The C3G Breakthrough: Discussion on the "wave of excitement" following adult trials for iptacopan and pegcetacoplan, and how these results are paving the way for pediatric use.SGLT2 Inhibitors in Children: Insights into the collaborative global effort that overcame initial industry waivers to launch a landmark clinical trial for SGLT2 inhibitors in children aged 2–17.Challenges in Rare Disease: Why international collaboration and registries are vital for treating ultra-rare conditions like Anti-GBM disease and C3G in small pediatric populations.The Future of Genetics: A look toward the next 15 years, where genetic screening may shift the focus from treating active disease to early prevention.Managing Long-term Immunosuppression: The delicate balance of using B-cell depletion (Rituximab) in developing immune systems to preserve "childhood" and avoid dialysis.Featured Guests Dr. Louise Oni: Professor of Pediatric Nephrology at Great Ormond Street and Chair of the ESPN Glomerular Disease Working Group.Dr. Jun Oh: Professor of Pediatrics at the University of Hamburg and a leader in the ISGD Pediatric Committee.Resources & Mentioned Studies International Society of Glomerular Disease (ISGD): Learn more about the society’s mission and join for free!ESPN Glomerular Disease Working Group: Clinical research and educational resources for pediatric nephrologists.NephCure: A key partner in driving global pediatric clinical trials and supporting families affected by rare kidney disease.APPEAR-C3G Trial (Iptacopan): Phase 3 study evaluating the first approved treatment for C3G.VALIANT Trial (Pegcetacoplan):  Recent Phase 3 results showing success in both adult and adolescent patients (12+), published in the New England Journal of Medicine.

    26 min
  5. Board Review Bonus #3: Lupus Nephritis

    10/23/2025 · BONUS

    Board Review Bonus #3: Lupus Nephritis

    In this Board Review Bonus episode of GN in Ten, hosts Dr. Kenar Jhaveri (Northwell Health/Hofstra University) and Dr. Koyal Jain (UNC Chapel Hill) dive into the crucial topic of Lupus Nephritis. Special guest, Northwell fellow Dr. Mahmoud Abdelaziz, asks Kenar and Koyal the tough questions about key topics in diagnosing and managing LN. Tune in to learn about diagnosis and initial suspicion of kidney involvement in Systemic Lupus Erythematosus (SLE), the six histological classifications (Class I-VI) of lupus nephritis, and an overview of induction and maintenance treatment algorithms for Class III and IV (proliferative) and Class V (membranous) lupus nephritis, including the use of reduced-dose glucocorticoids, MMF, cyclophosphamide (Euro-lupus vs. NIH protocols), and newer agents like voclosporin and belimumab. The GN in Ten hosts also discuss essential supportive care, like pneumocystic pneumonia prophylaxis (and the associated controversy with sulfamethoxazole/trimethoprim), multidisciplinary management, and management of special situations like pregnancy and Thrombotic Microangiopathy (TMA). Referenced Resources and Studies:KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisAmerican College of Rheumatology (ACR) Guidelines for Lupus Nephritis and Systemic Lupus Erythematosus Euro-Lupus Nephritis Trial and ProtocolNIH Lupus Nephritis Trial and ProtocolLUNAR Trial

    25 min

  6. 07/14/2025

    Episode 9: Carla Nester on C3 Glomerulopathy and Complement-Mediated Diseases

    In this episode, world-renowned complement expert Carla Nester (University of Iowa) joins Koyal and Kenar to discuss the state of the art in C3 glomerulopathy and other complement-mediated kidney diseases, the opportunities and unknowns of targeted treatments, the recent advances in understanding of all things complement, and how her med/peds specialization brings additional superpowers to her clinical practice. Dr. Nester is an adult and pediatric nephrologist, currently serving as Professor of Pediatrics and Internal Medicine in the Carver College of Medicine at the University of Iowa, where she also directs or co-directs the Molecular Otolaryngology and Renal Research Laboratory, Pediatric Glomerular Disease Clinic, Rare Renal Disease Clinic, and nephrology fellowship program. She specializes in the diagnosis, clinical management, and transplantation of complement-mediated kidney diseases, including C3 Glomerulopathy (C3G) and Atypical Hemolytic Uremic Syndrome (aHUS), and is a leading authority on the successful renal transplant protocol for aHUS patients. Her basic science research focuses on using unique complement functional assays to define complement dysregulation in patients with complement-mediated renal disease. Dr. Nester is co-chair of the SEISMIC Cross-Stakeholder Summit (AddreSsing accEss Issues in diagnoSis and treatMent of C3G nephropathy and IC-MPGN, July 17-19 2025), hosted by ISGD, NephCure and CompCure. To stay informed of the meeting results, sign up for the ISGD mailing list. Disclosures: Dr. Nester has disclosed the following relationships: Novartis: Research Grant Site Principal Investigator, Novartis: Consultant, Apellis: Research Grant Site Principal Investigator, Apellis: Consultant, Biocryst: Research Grant Site Principal Investigator, Biocryst: Consultant, Vertex: Scientific/Medical Advisory Board Member, Retrophin/Travere: Research Grant Site Principal Investigator, AstraZeneca: Consultant

    22 min

  7. 03/07/2025

    Episode 8: NephMadness 2025 Genetics Region

    In this special NephMadness 2025 episode, Koyal and Kenar do a deep dive into the Genetics region with NephMadness executive team member Elena Cervantes (Johns Hopkins), genetics expert Jordan Nestor (Columbia) and region writer Matt Gross (Johns Hopkins). Genetics in FSGS faces off vs. Genetic Counseling! What’s new in our ever-expanding knowledge of FSGS genetics? Where does APOL1 fit in? How should we be counseling patients before and after genetic testing, and are we actually getting the training we need to do so? And the big question: Which topic will change practice the most in the next five years? Tune in and then cast your NephMadness vote! https://ajkdblog.org/2025/03/01/welcome-to-nephmadness-2025/

    25 min

  8. 09/15/2024 · BONUS

    Board Review Bonus #2: Minimal Change Disease

    In this special bonus episode of the podcast, Koyal and Kenar provide a maximally useful review of minimal change disease, from diagnosis (including secondary causes to screen for) to treatment options, including how to decide which patients may do better with which therapies.  Can’t get enough minimal change? Check out Episode 6 (with Astrid Weins) and Episode 7 (with Felicitas Hengel and Nicola Tomas) for more on the potential role of anti-nephrin autoantibodies in MCD. References KDIGO guidelines: https://kdigo.org/wp-content/uploads/2017/02/KDIGO-GD-Guideline-Key-Takeaways-for-Clinicians-Minimal-Change-Disease.pdf Anti-nephrin autoantibodies: Kronbichler A, Barnini C, Matyjek A, Gauckler P, Bruchfeld A, Caravaca-Fontan F, Floege J, Frangou E, Mirioglu S, Moran SM, Stevens KI, Teng YKO, Steiger S. Antibody-mediated podocytopathies: a disease entity that implies immunotherapy. Nephrol Dial Transplant. 2024 Jul 17:gfae166. doi: 10.1093/ndt/gfae166. Epub ahead of print. PMID: 39020250. Hengel FE, Dehde S, Lassé M, Zahner G, Seifert L, Schnarre A, Kretz O, Demir F, Pinnschmidt HO, Grahammer F, Lucas R, Mehner LM, Zimmermann T, Billing AM, Oh J, Mitrotti A, Pontrelli P, Debiec H, Dossier C, Colucci M, Emma F, Smoyer WE, Weins A, Schaefer F, Alachkar N, Diemert A, Hogan J, Hoxha E, Wiech T, Rinschen MM, Ronco P, Vivarelli M, Gesualdo L, Tomas NM, Huber TB; International Society of Glomerular Disease. Autoantibodies Targeting Nephrin in Podocytopathies. N Engl J Med. 2024 May 25. doi: 10.1056/NEJMoa2314471. Epub ahead of print. PMID: 38804512.   Watts AJB, Keller KH, Lerner G, Rosales I, Collins AB, Sekulic M, Waikar SS, Chandraker A, Riella LV, Alexander MP, Troost JP, Chen J, Fermin D, Yee JL, Sampson MG, Beck LH Jr, Henderson JM, Greka A, Rennke HG, Weins A. Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology. J Am Soc Nephrol. 2022 Jan;33(1):238-252. doi: 10.1681/ASN.2021060794. Epub 2021 Nov 3. PMID: 34732507; PMCID: PMC8763186.

    25 min
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About

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.

Information

  • Creator
    International Society of Glomerular Disease
  • Years Active
    2023 - 2026
  • Episodes
    17
  • Rating
    Clean
  • Copyright
    © 2023 International Society of Glomerular Disease. All rights reserved.
  • Show Website
    GN in Ten

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