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. R