{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:47:34Z","timestamp":1786373254946,"version":"build-2736575974"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2021,12]]},"abstract":"\n Background and objectives<\/jats:title>\n \n Atrasentan reduces the risk of kidney failure but increases the risk of edema and, possibly, heart failure. Patients with severe CKD may obtain greater absolute kidney benefits from atrasentan but may also be at higher risk of heart failure. We assessed relative and absolute effects of atrasentan on kidney and heart failure events according to baseline eGFR and urinary albumin-creatinine ratio (UACR) in a\n post hoc<\/jats:italic>\n analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial.\n <\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n The effect of atrasentan versus placebo in 3668 patients with type 2 diabetes and CKD with elevated albuminuria was examined in the SONAR trial. We used Cox proportional hazards regression analysis to study effects on the primary kidney outcome (composite of doubling of serum creatinine, kidney failure, or kidney death) and heart failure hospitalization across subgroups of eGFR (<30, \u226530\u201345, and \u226545 ml\/min per 1.73 m\n 2<\/jats:sup>\n ) and UACR (<1000, \u22651000\u20133000, and \u22653000 mg\/g).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Atrasentan reduced the relative risk of the primary kidney outcome (hazard ratio, 0.71; 95% confidence interval, 0.58 to 0.88) consistently across all subgroups of baseline eGFR and UACR (all\n P<\/jats:italic>\n interaction >0.21). Patients in the highest UACR and lowest eGFR subgroups, in whom rates of the primary kidney outcome were highest, showed the largest absolute benefit (all\n P<\/jats:italic>\n interaction <0.01). The risk of heart failure hospitalization was higher in the atrasentan group (hazard ratio, 1.39; 95% confidence interval, 0.97 to 1.99) and was consistent across subgroups, with no evidence that relative or absolute risks differed across eGFR or UACR subgroups (all\n P<\/jats:italic>\n interaction >0.09).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Atrasentan reduced the relative risk of the primary kidney outcome consistently across baseline UACR and eGFR subgroups. The absolute risk reduction was greater among patients in the lowest eGFR and highest albuminuria category who were at highest baseline risk. Conversely, the relative and absolute risks of heart failure hospitalization were similar across baseline UACR and eGFR subgroups.<\/jats:p>\n \n Clinical Trial registry name and registration number:<\/jats:bold>\n Study of Diabetic Nephropathy with Atrasentan (SONAR), NCT01858532\n <\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.07340521","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T16:05:13Z","timestamp":1638374713000},"page":"1824-1832","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":22,"title":["The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function"],"prefix":"10.2215","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct01858532","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04724837","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04573920","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1717-0463","authenticated-orcid":false,"given":"Simke W.","family":"Waijer","sequence":"first","affiliation":[{"name":"Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron T.","family":"Gansevoort","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George L.","family":"Bakris","sequence":"additional","affiliation":[{"name":"American Society of Hypertension Comprehensive Hypertension Center, University of Chicago Medicine and Biological Sciences, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Correa-Rotter","sequence":"additional","affiliation":[{"name":"National Medical Science and Nutrition Institute Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan-Fan","family":"Hou","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald E.","family":"Kohan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Utah School of Medicine, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalane W.","family":"Kitzman","sequence":"additional","affiliation":[{"name":"Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Makino","sequence":"additional","affiliation":[{"name":"Okayama University, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlado","family":"Perkovic","sequence":"additional","affiliation":[{"name":"George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheldon","family":"Tobe","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Sunnybrook Health Sciences Centre, University of Toronto and the Northern Ontario School of Medicine, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Henrik","family":"Parving","sequence":"additional","affiliation":[{"name":"Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark"},{"name":"Faculty of Health Science, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick","family":"de Zeeuw","sequence":"additional","affiliation":[{"name":"Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiddo J.L.","family":"Heerspink","sequence":"additional","affiliation":[{"name":"Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"},{"name":"George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,12]]},"reference":[{"key":"B1-20241015","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1056\/NEJMoa011303","article-title":"Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes","volume":"345","author":"Lewis","year":"2001","journal-title":"N Engl J Med"},{"key":"B2-20241015","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1056\/NEJMoa011161","article-title":"Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and 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Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.2215\/CJN.07340521","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:44:04Z","timestamp":1786369444000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.2215\/CJN.07340521"}},"subtitle":["A Post Hoc Analysis of the SONAR Randomized Trial"],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":19,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.2215\/cjn.07340521","relation":{},"ISSN":["1555-9041","1555-905X"],"issn-type":[{"value":"1555-9041","type":"print"},{"value":"1555-905X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"2021-05-24","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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