3b:I[281230,["/_next/static/immutable/chunks/0l5c-zsrs2aic.js","/_next/static/immutable/chunks/3_n0rk2989-8h.js","/_next/static/immutable/chunks/3ofw495lt1gr1.js","/_next/static/immutable/chunks/3tofdpg99uc12.js","/_next/static/immutable/chunks/2rzojj6zgb9d9.js","/_next/static/immutable/chunks/42jxjvozn2thc.js","/_next/static/immutable/chunks/1jp6nkbajpbfs.js","/_next/static/immutable/chunks/3jn_lf7v27x-6.js","/_next/static/immutable/chunks/33qq2-hg37d0b.js","/_next/static/immutable/chunks/15isb0svrppbz.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/0asz50g5_lfq9.js","/_next/static/immutable/chunks/30ia-cxa0yoyc.js","/_next/static/immutable/chunks/3ghibkczd0agr.js","/_next/static/immutable/chunks/20mjl75wrar8n.js","/_next/static/immutable/chunks/3nxreg9fiyt2y.js","/_next/static/immutable/chunks/0c04lgvo3p78i.js","/_next/static/immutable/chunks/1u78gf_avpn77.js"],"PaperListPageClient"] 3e:I[70339,["/_next/static/immutable/chunks/355lxm8rh3fxr.js"],"IconMark"] 3c:T76a,Focal segmental glomerulosclerosis (FSGS) is a podocytopathy that is diagnosed based on characteristic histopathological lesions. Certain forms of FSGS with underlying genetic variants associated with the disease, including variants in podocyte proteins, as well as apolipoprotein L1 (APOL1) risk alleles, and variants in collagen type IV (COL4) α3, α4, and α5 (COL4A3-5) proteins, are typically resistant to current treatments. The DUPLEX clinical trial assessed the efficacy and safety of sparsentan, a dual endothelin angiotensin receptor antagonist (DEARA), in patients with biopsy-proven or genetic FSGS and demonstrated a greater antiproteinuric effect over 108 weeks compared to the active control irbesartan. This post hoc, exploratory analysis assessed the efficacy of sparsentan in the subset of patients enrolled in DUPLEX who had pathogenic variants in genes coding for podocyte proteins, COL4A3-5 variants, and APOL1 high-risk genotypes, altogether referred to as genetic FSGS (gFSGS). Next-generation sequencing identified 31 patients with podocyte gene variants, 25 with COL4A3-5 gene variants, and 14 with APOL1 high-risk genotypes. Baseline characteristics varied between genetic subgroups, with slightly younger patients, on average, in the podocyte gene variant group, and more African American patients in the APOL1 high-risk genotype group. In this exploratory analysis, sparsentan treatment resulted in substantial and sustained proteinuria reductions and numerically more frequent complete remission of proteinuria compared with irbesartan, consistent with observations in the full DUPLEX study population. Moreover, a lower proportion of sparsentan- vs irbesartan-treated patients reached composite kidney endpoints. These findings support sparsentan's antiproteinuric benefit in patients with gFSGS, a subgroup that is often resistant to other therapeutic interventions.3d:Tc8d, Background: Focal segmental glomerulosclerosis (FSGS) is a podocytopathy that is diagnosed based on characteristic histopathological lesions. Certain forms of FSGS with underlying genetic variants associated with the disease, including variants in podocyte proteins, as well as apolipoprotein L1 ( APOL1 ) risk alleles, and variants in collagen type IV (COL4) α3, α4, and α5 ( COL4A3-5 ) proteins, are typically resistant to current treatments. Methods: The DUPLEX clinical trial assessed the efficacy and safety of sparsentan, a dual endothelin angiotensin receptor antagonist (DEARA), in patients with biopsy-proven or genetic FSGS and demonstrated a greater antiproteinuric effect over 108 weeks compared to the active control irbesartan. This post hoc, exploratory analysis assessed the efficacy of sparsentan in the subset of patients enrolled in DUPLEX who had pathogenic variants in genes coding for podocyte proteins, COL4A3-5 variants, and APOL1 high-risk genotypes, altogether referred to as genetic FSGS (gFSGS). Results: Next-generation sequencing identified 31 patients with podocyte gene variants, 25 with COL4A3-5 gene variants, and 14 with APOL1 high-risk genotypes. Baseline characteristics varied between genetic subgroups, with slightly younger patients, on average, in the podocyte gene variant group, and more African American patients in the APOL1 high-risk genotype group. In this exploratory analysis, sparsentan treatment resulted in substantial and sustained proteinuria reductions and numerically more frequent complete remission of proteinuria compared with irbesartan, consistent with observations in the full DUPLEX study population. Moreover, a lower proportion of sparsentan- vs irbesartan-treated patients reached composite kidney endpoints. Conclusions: These findings support sparsentan’s antiproteinuric benefit in patients with gFSGS, a subgroup that is often resistant to other therapeutic interventions. 28:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Dual Endothelin Angiotensin Receptor Antagonist: Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Dual Endothelin Angiotensin Receptor Antagonist (modality). Clinician-written summaries and actionable practice insights. 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In the PROTECT OLE substudy, adding SGLT2i to sparsentan gave a modest but significant further reduction in urine protein-to-creatinine ratio vs. sparsentan alone at 12 weeks (ratio 0.75 [95% CI 0.58–0.98]; P<0.05). The combination was well tolerated with no unexpected safety signals.","limitations":"Both studies are short-term (12–24 weeks) with no hard renal endpoints (e.g., GFR decline or ESKD); SPARTACUS is single-arm with no direct comparator; PROTECT OLE substudy is relatively small (n=63).","practice_takeaway":"For IgAN patients already on an SGLT2 inhibitor, switching background RASi to sparsentan may offer substantially greater proteinuria reduction. Adding an SGLT2 inhibitor on top of stable sparsentan provides a modest, statistically significant additional antiproteinuric benefit with an acceptable safety profile."}},{"doi":"10.2215/cjn.0000000948","pmid":"41433094","title":"Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated Focal Segmental Glomerulosclerosis Enrolled in the DUPLEX Trial","journal_title":"Clinical Journal of the American Society of Nephrology","journal_issn":"1555-9041","published_at":"2025-12-23T00:00:00.000Z","url":"https://doi.org/10.2215/cjn.0000000948","source_score":31,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-12-24","doi":"10.2215/cjn.0000000948","days":"30","issn":"1555-9041","rank":"5","field":"Clinical Medicine","score":"31","category":"Urology & Nephrology","categories":["Urology & Nephrology"],"_categories":["Urology & Nephrology"]},"pubmed":{"doi":"10.2215/CJN.0000000948","title":"Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated Focal Segmental Glomerulosclerosis Enrolled in the DUPLEX Trial.","journal":"Clinical journal of the American Society of Nephrology : CJASN","methods":"","results":"Next-generation sequencing identified 31 patients with podocyte gene variants, 25 with COL4A3-5 gene variants, and 14 with APOL1 high-risk genotypes. Baseline characteristics varied between genetic subgroups, with slightly younger patients, on average, in the podocyte gene variant group, and more African American patients in the APOL1 high-risk genotype group. In this exploratory analysis, sparsentan treatment resulted in substantial and sustained proteinuria reductions and numerically more frequent complete remission of proteinuria compared with irbesartan, consistent with observations in the full DUPLEX study population. 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Therapeutics, Inc., San Diego, CA, USA"}]},{"given":"Jula","family":"Inrig","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, CA, USA"}]},{"given":"Michelle N","family":"Rheault","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA"}]},{"given":"Angela J","family":"Gruber","sequence":"additional","affiliation":[{"name":"PreventionGenetics, Marshfield, WI, USA"}]},{"given":"Patricia W","family":"Bedard","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, CA, USA"}]},{"given":"Radko","family":"Komers","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc., San Diego, CA, USA"}]},{"given":"Howard","family":"Trachtman","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA"}]}],"issued":{"date-parts":[[2025,12,23]]},"member":"276","prefix":"10.2215","source":"Crossref","volume":null,"created":{"date-time":"2025-12-23T17:00:44Z","timestamp":1766509244000,"date-parts":[[2025,12,23]]},"indexed":{"date-time":"2025-12-23T17:18:17Z","timestamp":1766510297847,"date-parts":[[2025,12,23]]},"license":[{"URL":"http://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000,"date-parts":[[2025,12,23]]},"delay-in-days":0,"content-version":"unspecified"}],"subject":[],"abstract":"$3d","language":"en","relation":{},"resource":{"primary":{"URL":"https://journals.lww.com/10.2215/CJN.0000000948"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","value":"2025-06-26"},{"name":"accepted","group":{"name":"publication_history","label":"Publication 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evaluated sparsentan versus irbesartan in participants with genetic-associated FSGS, including podocyte gene variants (n=31), COL4A3-5 variants (n=25), and APOL1 high-risk genotypes (n=14).","key_result":"Sparsentan produced substantial, sustained reductions in proteinuria, with numerically more complete remissions versus irbesartan, and a lower proportion reached composite kidney endpoints; no effect sizes were reported.","limitations":"Post hoc exploratory design with small genetic subgroups; baseline differences between groups (younger in the podocyte-variant group; more African American participants in the APOL1 group) may confound results.","practice_takeaway":"Findings support an antiproteinuric benefit of sparsentan in genetic FSGS, consistent with DUPLEX overall, but conclusions should be cautious due to exploratory subgroup analysis and small numbers."}}],"initialOffset":2,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Dual Endothelin Angiotensin Receptor 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