{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:42:09Z","timestamp":1792291329632,"version":"4.4.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2020,10]]},"abstract":"\n Background and objectives<\/jats:title>\n In the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG Outcome), empagliflozin, in addition to standard of care, significantly reduced risk of cardiovascular death by 38%, hospitalization for heart failure by 35%, and incident or worsening nephropathy by 39% compared with placebo in patients with type 2 diabetes and established cardiovascular disease. Using EMPA-REG Outcome data, we assessed whether the Kidney Disease Improving Global Outcomes (KDIGO) CKD classification had an influence on the treatment effect of empagliflozin.<\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n Patients with type 2 diabetes, established atherosclerotic cardiovascular disease, and eGFR\u226530 ml\/min per 1.73 m\n 2<\/jats:sup>\n at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care.\n Post hoc<\/jats:italic>\n , we analyzed cardiovascular and kidney outcomes, and safety, using the two-dimensional KDIGO classification framework.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 6952 patients with baseline eGFR and urinary albumin-creatinine ratio values, 47%, 29%, 15%, and 8% were classified into low, moderately increased, high, and very high KDIGO risk categories, respectively. Empagliflozin showed consistent risk reductions across KDIGO categories for cardiovascular outcomes (\n P<\/jats:italic>\n values for treatment by subgroup interactions ranged from 0.26 to 0.85) and kidney outcomes (\n P<\/jats:italic>\n values for treatment by subgroup interactions ranged from 0.16 to 0.60). In all KDIGO risk categories, placebo and empagliflozin had similar adverse event rates, the notable exception being genital infection events, which were more common with empagliflozin for each category.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The observed effects of empagliflozin versus placebo on cardiovascular and kidney outcomes were consistent across the KDIGO risk categories, indicating that the effect of treatment benefit of empagliflozin was unaffected by baseline CKD status.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n EMPA-REG OUTCOME, NCT01131676<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.14901219","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T19:55:39Z","timestamp":1601409339000},"page":"1433-1444","source":"Crossref","is-referenced-by-count":75,"title":["Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories"],"prefix":"10.2215","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct01131676","registry":"10.18810\/clinical-trials-gov","type":"results"},{"clinical-trial-number":"nct01131676","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03036150","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03594110","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Adeera","family":"Levin","sequence":"first","affiliation":[{"name":"Division of Nephrology, University of British Columbia, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlado","family":"Perkovic","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, Australia"},{"name":"Centre for Nephrology, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hantel","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyothis T.","family":"George","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH, Ingelheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"von Eynatten","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH, Ingelheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Koitka-Weber","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH, Ingelheim, Germany"},{"name":"Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia"},{"name":"Department of Medicine, W\u00fcrzburg University Clinic, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-5301","authenticated-orcid":false,"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"Department of Medicine, W\u00fcrzburg University Clinic, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the EMPA-REG OUTCOME Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"issue":"Suppl 1","key":"B1-20230813","first-page":"S14","article-title":"Standards of medical care in diabetes\u20142014","volume":"37","year":"2014","journal-title":"Diabetes Care"},{"key":"B2-20230813","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1001\/jama.2011.861","article-title":"Temporal trends in the prevalence of diabetic kidney disease in the United 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