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.

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 Nephritis
American College of Rheumatology (ACR) Guidelines for Lupus Nephritis and Systemic Lupus Erythematosus
Euro-Lupus Nephritis Trial and Protocol
NIH Lupus Nephritis Trial and Protocol
LUNAR Trial

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

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/

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.

In this episode, we talk with Dr. Felicitas Hengel, MD and Dr. Nicola Tomas, MD (both at the University Medical Center Hamburg-Eppendorf) about their groundbreaking anti-nephrin autoantibody research that was just presented at the 2024 ERA Congress and published in the New England Journal of Medicine. Is this a game-changer for minimal change? How could this new understanding change diagnosis and treatment in the future? Are anti-nephrin autoantibodies the next PLA2R? What are the next steps for follow-up studies? And how do you do a big international study like this, anyway?

References:

The study:

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.

More information on the research, including additional Q&A with the authors: https://www.is-gd.org/anti-nephrin-autoantibodies

Previous research by Astrid Weins:

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.

In this episode, Kenar and Koyal interview Dr. Astrid Weins, MD, PhD, about nephropathology, new approaches to solving the mysteries of nephrotic syndrome, and her research on anti-nephrin antibodies in minimal change disease. Dr. Weins is Chief of Integrated Renal Pathology at Mass General/Brigham and an Assistant Professor of Pathology at Harvard.

Interested in this topic? Stay tuned for additional new research on anti-nephrin antibodies that will be presented in a Late-Breaking Clinical Trials session on May 25 at the 2024 ERA Congress.

References:

2022 JASN paper proposing nephrin auti-antibodies in MCD:

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.

Examples of Julie Goodwin and Bill Smoyer’s work on the podocyte’s response to steroids:

Zhou H, Tian X, Tufro A, Moeckel G, Ishibe S, Goodwin J. Loss of the podocyte glucocorticoid receptor exacerbates proteinuria after injury. Sci Rep. 2017 Aug 29;7(1):9833. doi: 10.1038/s41598-017-10490-z. PMID: 28852159; PMCID: PMC5575043.

Bhayana S, Zhao Y, Merchant M, Cummins T, Dougherty JA, Kamigaki Y, Pathmasiri W, McRitchie S, Mariani LH, Sumner S, Klein JB, Li L, Smoyer WE; Pediatric Nephrology Research Consortium. Multiomics Analysis of Plasma Proteomics and Metabolomics of Steroid Resistance in Childhood Nephrotic Syndrome Using a "Patient-Specific" Approach. Kidney Int Rep. 2023 Mar 23;8(6):1239-1254. doi: 10.1016/j.ekir.2023.03.015. PMID: 37284673; PMCID: PMC10239920.

Pediatric cohort and rapid response to corticosteroids:

Circulating Nephrin Autoantibodies Are Present in Almost 2/3 of Steroid-Naïve Pediatric Idiopathic Nephrotic Syndrome. Presented at ASN Kidney Week 2023, abstract: SA-OR80. https://www.asn-online.org/education/kidneyweek/2023/program-abstract.aspx?controlId=3946457