Episode 6: Astrid Weins on Anti-Nephrin Antibodies and Nephropathology

05/17/24 • 17 min

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

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:

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

Pediatric cohort and rapid response to corticosteroids:

Previous Episode

undefined - Episode 5: Industry Perspective with Jula Inrig: Endothelin Antagonism, IgAN, FSGS, Clinical Trial Career Paths, and the New Era of Nephrology Trials

Episode 5: Industry Perspective with Jula Inrig: Endothelin Antagonism, IgAN, FSGS, Clinical Trial Career Paths, and the New Era of Nephrology Trials

In this episode, Kenar and Koyal talk with Dr. Jula Inrig about endothelin physiology and different approaches to endothelin antagonism, trials of sparsentan in IgAN and FSGS, the art and science of clinical trial design, career paths in clinical research outside academia, and how we got to our current era of plentiful nephrology clinical trials.

Disclosure: Jula Inrig is the Chief Medical Officer of Travere Therapeutics, which is one of multiple corporate partners that provide financial support to ISGD. Dr. Inrig also serves independently on the ISGD Steering Committee as a representative of industry. Travere had no role in developing the interview questions, editing the episode, or otherwise determining the content of this podcast.

References

SONAR trial and effects of endothelin-A antagonism on heart failure:

Waijer SW, Gansevoort RT, Bakris GL, Correa-Rotter R, Hou FF, Kohan DE, Kitzman DW, Makino H, McMurray JJV, Perkovic V, Tobe S, Parving HH, de Zeeuw D, Heerspink HJL. The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function: A Post Hoc Analysis of the SONAR Randomized Trial. Clin J Am Soc Nephrol. 2021 Dec;16(12):1824-1832. doi: 10.2215/CJN.07340521. Epub 2021 Dec 1. PMID: 34853062; PMCID: PMC8729501.

PROTECT trial:

Rovin BH, Barratt J, Heerspink HJL, Alpers CE, Bieler S, Chae DW, Diva UA, Floege J, Gesualdo L, Inrig JK, Kohan DE, Komers R, Kooienga LA, Lafayette R, Maes B, Małecki R, Mercer A, Noronha IL, Oh SW, Peh CA, Praga M, Preciado P, Radhakrishnan J, Rheault MN, Rote WE, Tang SCW, Tesar V, Trachtman H, Trimarchi H, Tumlin JA, Wong MG, Perkovic V; DUPRO steering committee and PROTECT Investigators. Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial. Lancet. 2023 Dec 2;402(10417):2077-2090. doi: 10.1016/S0140-6736(23)02302-4. Epub 2023 Nov 3. PMID: 37931634.

DUPLEX trial:

Rheault MN, Alpers CE, Barratt J, Bieler S, Canetta P, Chae DW, Coppock G, Diva U, Gesualdo L, Heerspink HJL, Inrig JK, Kirsztajn GM, Kohan D, Komers R, Kooienga LA, Lieberman K, Mercer A, Noronha IL, Perkovic V, Radhakrishnan J, Rote W, Rovin B, Tesar V, Trimarchi H, Tumlin J, Wong MG, Trachtman H; DUPRO Steering Committee and DUPLEX Investigators. Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. N Engl J Med. 2023 Dec 28;389(26):2436-2445. doi: 10.1056/NEJMoa2308550. Epub 2023 Nov 3. PMID: 37921461.

Using sparsentan in treatment-naive early IgA patients (SPARTAN trial):

Sparsentan as First-Line Treatment of Incident Patients with IgA Nephropathy: Preliminary Findings from the SPARTAN Trial (ASN Kidney Week 2023 session, abstract SA-PO901) https://www.asn-online.org/education/kidneyweek/2023/program-abstract.aspx?controlId=3940774

KHI project defining the relationship between proteinuria, GFR, and kidney failure in IgAN:

Thompson A, Carroll K, A Inker L, Floege J, Perkovic V, Boyer-Suavet S, W Major R, I Schimpf J, Barratt J, Cattran DC, S Gillespie B, Kausz A, W Mercer A, Reich HN, H Rovin B, West M, Nachman PH. Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy. Clin J Am Soc Nephrol. 2019 Mar 7;14(3):469-481. doi: 10.2215/CJN.08600718. Epub 2019 Jan 11. PMID: 30635299; PMCID: PMC6419287.

KHI project for FSGS endpoints:

https://khi.asn-online.org/projects/project.aspx?ID=74

PARASOL Project: https://www.is-gd.org/parasol

FLOW trial:

Rossing P, Baeres FMM, Bakris G, Bosch-Traberg H, Gislum M, Gough SCL, Idorn T, Lawson J, Mahaffey KW, Mann JFE, Mersebach H, Perkovic V, Tuttle K, Pratley R. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease. Nephrol Dial Transplant. 2023 Aug 31;38(9):2041-2051. doi: 10.1093/ndt/gfad009. Erratum in: Nephrol Dial Transplant. 2024 Mar 27;39(4):724. PMID: 36651820; PMCID: PMC10469096.

RaDaR: https://ukkidney.org/rare-renal/radar

Clinical trials in nephrology compared to other specialties:

Inrig JK, Califf RM, Tasneem A, Vegunta RK, Molina C, Stanifer JW, Chiswell K, Patel UD. The landscape of clinical trials in nephrology: a systematic review of Clinicaltrials.gov. Am J Kidney Dis. 2014 May;63(5):771-80. doi: 10.1053/j.ajkd.2013.10.043. Epub 2013 Dec 6. PMID: 24315119; PMCID: PMC3988265.

Clinical Trials in Nephrology: An Updated Systematic Review of ClinicalTrials.gov (ASN Kidney Week 2019 session, abstract FR-PO1199)

Next Episode

Episode 7: Felicitas Hengel and Nicola Tomas on a New Chapter in Anti-Nephrin Autoantibodies

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:

GN in Ten - Episode 6: Astrid Weins on Anti-Nephrin Antibodies and Nephropathology

Transcript

Laurel Damashek00:00:01.000

Welcome to GN in Ten, a bite sized podcast brought to you by the International Society of Glomerular Disease. Our hosts are nephrologists and glomerular disease experts Dr. Kenar Jhaveri of Northwell Health and Hofstra University on Long Island, New York, and Dr. Koyal Jain from the University of North Carolina Chapel Hill.

Koyal Jain00:00:24.410

Welcome everybody. We are so excited. These are your favorite h