2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30: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.31: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. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Dual Endothelin Angiotensin Receptor Antagonist: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Dual Endothelin Angiotensin Receptor Antagonist (modality). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/modality/Dual%20Endothelin%20Angiotensin%20Receptor%20Antagonist\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Modalities\",\"item\":\"https://www.reachrx.ai/hub/tag/modality\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Dual Endothelin Angiotensin Receptor Antagonist\",\"item\":\"https://www.reachrx.ai/hub/tag/modality/Dual%20Endothelin%20Angiotensin%20Receptor%20Antagonist\"}]}}"}}]],["$","$L2f",null,{"title":"Dual Endothelin Angiotensin Receptor Antagonist: Research & Clinical Takeaways","description":"Review evidence by treatment modality: Dual Endothelin Angiotensin Receptor Antagonist — concise summaries and practical next steps.","papers":[{"doi":"10.1093/ndt/gfag211","pmid":"42726023","title":"Sparsentan - SGLT2 inhibitor combination therapy in trials of IgA nephropathy","journal_title":"Nephrology Dialysis Transplantation","journal_issn":"0931-0509","published_at":"2026-09-11T00:00:00.000Z","url":"https://doi.org/10.1093/ndt/gfag211","source_score":10,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-16T06:22:56.700Z","updated_at":"2026-09-16T06:22:56.700Z","tags":[{"paper_doi":"10.1093/ndt/gfag211","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"brand","value":"Filspari","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"condition","value":"IgA Nephropathy","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"generic","value":"sparsentan","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"modality","value":"Dual Endothelin Angiotensin Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"modality","value":"SGLT2 Inhibitor","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"sample_size","value":"n=111","value_numeric":111},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"study_design","value":"Phase 2 Open-Label Trial with Randomized Substudy","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"warning","value":"Proteinuria surrogates are used as endpoints; long-term renal outcomes (eGFR trajectories, ESKD) are not reported.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"warning","value":"SPARTACUS is a single-arm study (no RASi-continuation comparator), limiting causal attribution of proteinuria reduction to the sparsentan switch alone.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"warning","value":"The brand name 'Filspari' is inferred for sparsentan based on known approvals; it is not explicitly stated in the abstract.","value_numeric":null},{"paper_doi":"10.1093/ndt/gfag211","tag_type":"warning","value":"The total sample size of n=111 is derived by combining SPARTACUS (n=48) and PROTECT OLE substudy (n=63); these are separate trial populations and should not be pooled clinically.","value_numeric":null}],"summaries":{"what_studied":"Two trials evaluated sparsentan + SGLT2 inhibitor combination in IgA nephropathy: SPARTACUS (phase 2, open-label; RASi replaced by sparsentan while continuing SGLT2i, 24 weeks, n=48) and a PROTECT OLE substudy (randomized 12-week addition of SGLT2i vs. sparsentan alone, followed by 24-week open combination phase, n=63).","key_result":"In SPARTACUS, switching from RASi to sparsentan on background SGLT2i cut urine albumin-to-creatinine ratio by 56% at 24 weeks. 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. Moreover, a lower proportion of sparsentan- vs irbesartan-treated patients reached composite kidney endpoints.","abstract":"$30","keywords":[],"pubmed_id":"41433094","conclusions":"","publication_date":"2025-12-23T00:00:00"},"crossref":{"DOI":"10.2215/cjn.0000000948","URL":"https://doi.org/10.2215/cjn.0000000948","ISSN":["1555-9041","1555-905X"],"link":[{"URL":"https://journals.lww.com/10.2215/CJN.0000000948","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated Focal Segmental Glomerulosclerosis Enrolled in the DUPLEX Trial"],"author":[{"given":"Jennifer","family":"Yee","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA"}]},{"given":"Wu","family":"Gong","sequence":"additional","affiliation":[{"name":"Travere 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":"$31","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 History"},"label":"Accepted","value":"2025-12-18"}],"deposited":{"date-time":"2025-12-23T17:00:44Z","timestamp":1766509244000,"date-parts":[[2025,12,23]]},"issn-type":[{"type":"print","value":"1555-9041"},{"type":"electronic","value":"1555-905X"}],"published":{"date-parts":[[2025,12,23]]},"publisher":"Ovid Technologies (Wolters Kluwer Health)","reference":null,"short-title":[],"update-policy":"https://doi.org/10.1097/lww.0000000000001000","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Clinical Journal of the American Society of Nephrology"],"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,12,23]]},"references-count":0,"short-container-title":["CJASN"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.2215/cjn.0000000948","is_oa":true,"title":"Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated Focal Segmental Glomerulosclerosis Enrolled in the DUPLEX Trial","updated":"2025-12-24T00:55:44+00:00","published_date":"2025-12-23","best_oa_location":{"url":"https://doi.org/10.2215/cjn.0000000948","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.2215/cjn.0000000948"}}},"created_at":"2026-01-11T11:19:33.869Z","updated_at":"2026-01-21T12:05:26.220Z","tags":[{"paper_doi":"10.2215/cjn.0000000948","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"condition","value":"Focal Segmental Glomerulosclerosis","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"generic","value":"irbesartan","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"generic","value":"sparsentan","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"modality","value":"Angiotensin Receptor Blocker","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"modality","value":"Dual Endothelin Angiotensin Receptor Antagonist","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"study_design","value":"Post Hoc Analysis","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"warning","value":"No numeric effect sizes or event counts were provided in the abstract.","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"warning","value":"Results are from an exploratory post hoc subgroup analysis of an RCT.","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"warning","value":"Subgroup counts may overlap; total N for genetic FSGS was not specified.","value_numeric":null},{"paper_doi":"10.2215/cjn.0000000948","tag_type":"warning","value":"Timeframe for subgroup outcomes was not explicitly stated.","value_numeric":null}],"summaries":{"what_studied":"Post hoc, exploratory analysis of DUPLEX 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 Antagonist"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Dual Endothelin Angiotensin Receptor Antagonist"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Dual Endothelin Angiotensin Receptor Antagonist"}}}]]

Papers