{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:45:24Z","timestamp":1791251124503,"version":"4.1.0"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novartis"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,9]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n Patients with IgA nephropathy and proteinuria are at risk of kidney failure despite use of guideline-recommended renin-angiotensin system and sodium-glucose cotransporter 2 (SGLT2) inhibition.<\/jats:p>\n <\/jats:list-item>\n \n Atrasentan reduces proteinuria in IgA nephropathy, but its efficacy as adjunct to renin-angiotensin system and SGLT2 inhibition has not been rigorously tested.<\/jats:p>\n <\/jats:list-item>\n \n Atrasentan provided a clinically meaningful reduction in proteinuria in adults with IgA nephropathy treated with renin-angiotensin system and SGLT2 inhibitors.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Atrasentan, a highly selective endothelin-A receptor antagonist, is approved for proteinuria reduction in adults with IgA nephropathy. Renin-angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are guideline recommended, yet the additional benefit of atrasentan has not been rigorously determined.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We performed a randomized, double-blind, placebo-controlled crossover study of atrasentan in adults with IgA nephropathy, eGFR \u226530 ml\/min per 1.73 m\n 2<\/jats:sup>\n , and urinary protein >0.5 g\/d while on maximal, stable RASi and SGLT2i. Participants were randomized 1:1 to either sequence AB or sequence BA (0.75 mg atrasentan [A] once daily during period 1 and matching placebo [B] during period 2, or vice versa), with a 12-week washout period in between. The primary end point was the change in urinary protein-to-creatinine ratio (UPCR) to week 12. The secondary end point was the change in UPCR to week 24. Safety end points included the type, incidence, severity, seriousness, and relatedness of adverse events (AEs).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We recruited 54 participants with mean age 48 years (SD 12), 43% female, mean (SD) eGFR 63 (22) ml\/min per 1.73 m\n 2<\/jats:sup>\n , and median UPCR 1.0 g\/g (Q1\u2013Q3, 0.7\u20131.4). Treatment with atrasentan versus placebo resulted in a difference in geometric mean percentage change in UPCR at week 12 of \u221225.3% (95% confidence interval, \u221236.8 to \u221211.7;\n P <<\/jats:italic>\n 0.001). The treatment difference in UPCR between atrasentan versus placebo during treatment period 2 at week 24 was \u221226.4% (95% confidence interval, \u221245.8 to \u22120.0). There was one unrelated serious adverse event. Fluid retention events were uncommon, and none required hospitalization. There were no study drug discontinuations due to treatment-related adverse events and no deaths.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Atrasentan provided a clinically meaningful reduction in proteinuria in adults with IgA nephropathy and proteinuria \u22650.5 g\/d treated with RASi and SGLT2i therapy. Atrasentan was well tolerated, and no new safety signals emerged.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n NCT05834738.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001076","type":"journal-article","created":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T06:00:09Z","timestamp":1774764009000},"page":"2004-2015","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy and Safety of Atrasentan in Patients with IgA Nephropathy Receiving Sodium-Glucose Cotransporter 2 Inhibitors"],"prefix":"10.1681","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J.L.","family":"Heerspink","sequence":"first","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3208-4435","authenticated-orcid":false,"given":"Irene L.","family":"Noronha","sequence":"additional","affiliation":[{"name":"Renal Division, University of S\u00e3o Paulo Medical School, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1134-9051","authenticated-orcid":false,"given":"Jose Luis","family":"G\u00f3rriz","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico Universitario, INCLIVA Biomedical Research Institute, Valencia, Spain"},{"name":"Universidad de Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7589-5150","authenticated-orcid":false,"given":"Soo Kun","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3294-4087","authenticated-orcid":false,"given":"Sradha S.","family":"Kotwal","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Nephrology, Prince of Wales Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1317-4109","authenticated-orcid":false,"given":"Gianna M.","family":"Kirsztajn","sequence":"additional","affiliation":[{"name":"Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2197-6809","authenticated-orcid":false,"given":"Jos\u00e9","family":"Barros Neto","sequence":"additional","affiliation":[{"name":"Clinical Nephrology Department of the Brazilian Society of Nephrology, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2007-6021","authenticated-orcid":false,"given":"Jessica","family":"Ryan","sequence":"additional","affiliation":[{"name":"Monash Health, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Sian","family":"Fu","sequence":"additional","affiliation":[{"name":"Hospital Sultanah Aminah, Johor Bahru, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5034-0527","authenticated-orcid":false,"given":"Sung-Gyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Hallym University Sacred Heart Hospital, Anyang, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9063-7229","authenticated-orcid":false,"given":"Jonathan","family":"Barratt","sequence":"additional","affiliation":[{"name":"The Mayer IgA Nephropathy Laboratories, University of Leicester, Leicester, United Kingdom"},{"name":"The John Walls Renal Unit, Leicester General Hospital, Leicester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Brahmbhatt","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1151-7166","authenticated-orcid":false,"given":"Greggory J.","family":"Housler","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Jiao","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1360-6382","authenticated-orcid":false,"given":"Marion","family":"Dahlke","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Lodha","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4258-1726","authenticated-orcid":false,"given":"Amy K.","family":"Mottl","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Atrasentan and Sodium Glucose Cotransporter-2 Inhibitor Efficacy and Safety Trial (ASSIST) Investigator Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"issue":"6","key":"B1-20260901","doi-asserted-by":"crossref","first-page":"e38904","DOI":"10.1371\/journal.pone.0038904","article-title":"Predicting progression of IgA nephropathy: new clinical progression risk score","volume":"7","author":"Xie","year":"2012","journal-title":"PLoS One."},{"issue":"6","key":"B2-20260901","doi-asserted-by":"crossref","first-page":"727","DOI":"10.2215\/CJN.0000000000000135","article-title":"Long-term outcomes in IgA nephropathy","volume":"18","author":"Pitcher","year":"2023","journal-title":"Clin J Am Soc Nephrol."},{"issue":"4S","key":"B3-20260901","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.kint.2025.04.004","article-title":"KDIGO 2025 clinical practice guideline for the management of immunoglobulin A nephropathy (IgAN) and immunoglobulin A vasculitis (IgAV)","volume":"108","author":"Rovin","year":"2025","journal-title":"Kidney Int"},{"issue":"4","key":"B4-20260901","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1097\/MNH.0000000000000716","article-title":"Endothelin receptor antagonists for the treatment of diabetic and nondiabetic chronic kidney disease","volume":"30","author":"Smeijer","year":"2021","journal-title":"Curr Opin Nephrol Hypertens."},{"issue":"3","key":"B5-20260901","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41581-024-00908-z","article-title":"Endothelin receptor antagonists in chronic kidney disease","volume":"21","author":"Smeijer","year":"2025","journal-title":"Nat Rev 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nephropathy","volume":"14","author":"Thompson","year":"2019","journal-title":"Clin J Am Soc Nephrol."},{"issue":"3","key":"B15-20260901","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1053\/j.ajkd.2021.03.007","article-title":"Association of treatment effects on early change in urine protein and treatment effects on GFR slope in IgA nephropathy: an individual participant meta-analysis","volume":"78","author":"Inker","year":"2021","journal-title":"Am J Kidney Dis."}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001076","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:00:36Z","timestamp":1788282036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001076"}},"subtitle":["Placebo-Controlled, Crossover Trial"],"short-title":[],"issued":{"date-parts":[[2026,3,29]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.0000001076","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,29]]},"assertion":[{"value":"2026-02-06","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-10","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}