Episodit
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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.
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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
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Puuttuva jakso?
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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)
https://www.asn-online.org/education/kidneyweek/2019/program-abstract.aspx?controlId=3237149
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It's March, and that means it's time for NephMadness! Every year, our friends at AJKDBlog pit 16 unique regions of nephrology against each other in a basketball-style tournament. Prepare for the Preeclampsia region by listening to this special episode, where Anna Burgner from Vanderbilt University joins Kenar and Koyal to discuss recent discoveries in preeclampsia (the world's most common glomerulopathy).
Will the victor be Diagnosis and Treatment of Preeclampsia, or Risk Factors, Prevention, and Long-Term Sequelae in Preeclampsia? Learn more at ajkdblog.org and submit your picks at nephmadness.com by March 31!
References:
1. de Jesús GR, Lacerda MI, Rodrigues BC, Dos Santos FC, do Nascimento AP, Cristóvão Porto L, de Jesús NR, Levy RA, Klumb EM. Soluble Flt-1, Placental Growth Factor, and Vascular Endothelial Growth Factor Serum Levels to Differentiate Between Active Lupus Nephritis During Pregnancy and Preeclampsia. Arthritis Care Res (Hoboken). 2021 May;73(5):717-721. doi: 10.1002/acr.24360. Epub 2021 Apr 3. PMID: 32583963.
2. Cross SN, Ratner E, Rutherford TJ, Schwartz PE, Norwitz ER. Bevacizumab-mediated interference with VEGF signaling is sufficient to induce a preeclampsia-like syndrome in nonpregnant women. Rev Obstet Gynecol. 2012;5(1):2-8. PMID: 22582121; PMCID: PMC3349918.
3. Wiles K, Bramham K, Seed PT, Brockbank A, Nelson-Piercy C, Karumanchi SA, Lightstone L, Chappell LC. Placental and endothelial biomarkers for the prediction of superimposed pre-eclampsia in chronic kidney disease. Pregnancy Hypertens. 2021 Jun;24:58-64. doi: 10.1016/j.preghy.2021.02.010. Epub 2021 Feb 23. PMID: 33677420.
4. Tita AT, Szychowski JM, Boggess K, Dugoff L, Sibai B, Lawrence K, Hughes BL, Bell J, Aagaard K, Edwards RK, Gibson K, Haas DM, Plante L, Metz T, Casey B, Esplin S, Longo S, Hoffman M, Saade GR, Hoppe KK, Foroutan J, Tuuli M, Owens MY, Simhan HN, Frey H, Rosen T, Palatnik A, Baker S, August P, Reddy UM, Kinzler W, Su E, Krishna I, Nguyen N, Norton ME, Skupski D, El-Sayed YY, Ogunyemi D, Galis ZS, Harper L, Ambalavanan N, Geller NL, Oparil S, Cutter GR, Andrews WW; Chronic Hypertension and Pregnancy (CHAP) Trial Consortium. Treatment for Mild Chronic Hypertension during Pregnancy. N Engl J Med. 2022 May 12;386(19):1781-1792. doi: 10.1056/NEJMoa2201295. Epub 2022 Apr 2. PMID: 35363951; PMCID: PMC9575330.
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We talk with Dr. Opeyemi Olabisi, MD, PhD, about the history and future of APOL1-mediated FSGS, the role of clinical researchers in building trust with patients, his innovative CARE and JUSTICE programs to bring kidney health screenings and research opportunities to the underrepresented African American community, and why his expertise as an MD/PhD in molecular biology led him to also become a leader in community engagement. The JAK-STAT pathway gets some love as well!
Dr. Olabisi's research and publications: https://medicine.duke.edu/profile/opeyemi-olabisi
More information on the CARE and JUSTICE studies: https://kidneycareandjustice.com/Disclosures: Dr. Olabisi reports receiving research funding from NIH and Icagen, and consulting for Maze Therapeutics and Podium Bio.
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In this episode of GN in Ten, Koyal and Kenar take the show on the road to Kidney Week to ask attendees about their favorite glomerular diseases. Listen closely for a surprise Shakespearean crossover!
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International Society of Glomerular Disease President Prof. Dr. Tobias B. Huber of the University Medical Center Hamburg-Eppendorf discusses the mission of the society and his vision for the future of glomerular disease.
More information on the Hamburg Center for Kidney HealthCreators & Guests
Kenar Jhaveri - Host Koyal Jain - Host Tobias B. Huber - Guest Laurel Damashek - Producer -
Welcome to GN in Ten from the International Society of Glomerular Disease! In this trailer, our hosts Dr. Kenar Jhaveri and Dr. Koyal Jain introduce themselves and the podcast.
Learn more about the International Society of Glomerular Disease (ISGD) at is-gd.org.
