{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:05:45Z","timestamp":1787313945027,"version":"build-2736575974"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The CONFIDENCE (COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with CKD and type 2 diabetes using a UACR Endpoint) trial investigated the safety and efficacy of simultaneously initiating finerenone and empagliflozin for patients with chronic kidney disease (CKD) and type 2 diabetes. This prespecified analysis aimed to determine if the predicted risk of kidney disease progression, based on KDIGO risk categories, influenced the benefits and safety of this combination therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The double-blind, double-dummy trial randomized 818 adults with CKD and type 2 diabetes [urine albumin\u2013creatinine ratio (UACR) \u2265100 to &amp;lt;5000\u00a0mg\/g] to receive once-daily finerenone plus empagliflozin, finerenone alone or empagliflozin alone, all in addition to a renin\u2013angiotensin system inhibitor. The relative change in UACR from baseline to day 180 (primary endpoint) and a &amp;gt;30% reduction in UACR (secondary endpoint) across KDIGO risk categories was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At baseline, among 781 with available data, 11.3% of participants were classified as low\/moderate risk, 29.6% as high risk and 59.2% as very high risk. At 180 days, combination therapy significantly reduced UACR levels across all KDIGO risk categories (low\/moderate: \u201361.7%; high: \u201360.7%; very high: \u201352.4%). This reduction was consistently greater than that achieved with either monotherapy alone. More than half of patients on combination therapy experienced UACR reductions of &amp;gt;30% (low\/moderate: 58.1%; high: 74.2%; very high: 70.6%), again outperforming monotherapies across all risk groups. While hyperkalemia was more common with combination therapy, early eGFR declines (&amp;gt;30% within 30 days) were less frequent in individuals with higher KDIGO risk compared with lower risk. Overall, the safety profile of combination therapy remained consistent across all KDIGO risk categories, with no unexpected safety signals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The CONFIDENCE trial demonstrates that the relative efficacy and safety of simultaneous finerenone and empagliflozin combination therapy are consistent across a wide spectrum of predicted kidney disease risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>NCT05254002; EudraCT 2021-003037-11<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfaf160","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T11:50:09Z","timestamp":1755085809000},"page":"161-170","source":"Crossref","is-referenced-by-count":7,"title":["Simultaneous initiation of finerenone and empagliflozin across the spectrum of kidney risk in the CONFIDENCE trial"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0885-1953","authenticated-orcid":false,"given":"Muthiah","family":"Vaduganathan","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer B","family":"Green","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine Division of Endocrinology, Department of Medicine and Duke Clinical Research Institute, , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J L","family":"Heerspink","sequence":"additional","affiliation":[{"name":"University of Groningen and University Medical Center Groningen Department Clinical Pharmacy and Pharmacology, , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Gyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Hallym University Sacred Heart Hospital , Anyang ,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes F E","family":"Mann","sequence":"additional","affiliation":[{"name":"KfH (Kuratorium f\u00fcr Dialyse und Nierentransplantation) Kidney Center , Munich ,","place":["Germany"]},{"name":"Friedrich Alexander University Department of Nephrology and Hypertension, , Erlangen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet B","family":"McGill","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Lipid Research, Washington University in St Louis , St Louis, MO ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Mottl","sequence":"additional","affiliation":[{"name":"University of North Carolina (UNC) Kidney Center, UNC School of Medicine , Chapel Hill, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7401-2934","authenticated-orcid":false,"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8324-3275","authenticated-orcid":false,"given":"Julio","family":"Rosenstock","sequence":"additional","affiliation":[{"name":"Velocity Clinical Research at Medical City , Dallas, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-4294","authenticated-orcid":false,"given":"Peter","family":"Rossing","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen and University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Bayer AG , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Bayer Healthcare , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Rohwedder","sequence":"additional","affiliation":[{"name":"Bayer AG , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Scott","sequence":"additional","affiliation":[{"name":"Bayer Healthcare Inc. , Whippany, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-7100","authenticated-orcid":false,"given":"Rajiv","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Richard L. Roudebush VA Medical Center, Indianapolis Indiana University School of Medicine , Indianapolis ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"2025122223464940200_bib1","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/j.kint.2019.07.012","article-title":"A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases","volume":"96","author":"Jager","year":"2019","journal-title":"Kidney Int"},{"key":"2025122223464940200_bib2","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/S0140-6736(13)60687-X","article-title":"Chronic kidney disease: global dimension and perspectives","volume":"382","author":"Jha","year":"2013","journal-title":"Lancet"},{"key":"2025122223464940200_bib3","doi-asserted-by":"publisher","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","year":"2024","journal-title":"Kidney Int"},{"key":"2025122223464940200_bib4","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1001\/jama.2023.17002","article-title":"Estimated glomerular filtration rate, albuminuria, and adverse outcomes: an individual-participant data meta-analysis","volume":"330","author":"Writing Group for the CKD Prognosis Consortium","year":"2023","journal-title":"JAMA"},{"key":"2025122223464940200_bib5","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1016\/S0140-6736(22)02074-8","article-title":"Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials","volume":"400","author":"Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists\u2019 Consortium","year":"2022","journal-title":"Lancet"},{"key":"2025122223464940200_bib6","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1093\/eurheartj\/ehab777","article-title":"Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis","volume":"43","author":"Agarwal","year":"2022","journal-title":"Eur Heart J"},{"key":"2025122223464940200_bib7","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1056\/NEJMoa2403347","article-title":"Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes","volume":"391","author":"Perkovic","year":"2024","journal-title":"N Engl J Med"},{"key":"2025122223464940200_bib8","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1161\/CIRCULATIONAHA.123.068524","article-title":"Accelerated risk-based implementation of guideline-directed medical therapy for type 2 diabetes and chronic kidney disease","volume":"149","author":"Neuen","year":"2024","journal-title":"Circulation"},{"key":"2025122223464940200_bib9","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1056\/NEJMoa2410659","article-title":"Finerenone with empagliflozin in chronic kidney disease and type 2 diabetes","volume":"393","author":"Agarwal","year":"2025","journal-title":"N Engl J Med"},{"key":"2025122223464940200_bib10","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1093\/ndt\/gfac198","article-title":"Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE)","volume":"38","author":"Green","year":"2023","journal-title":"Nephrol Dial Transplant"},{"key":"2025122223464940200_bib11","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1093\/ndt\/gfaf022","article-title":"COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint (CONFIDENCE) trial: baseline clinical characteristics","volume":"40","author":"Agarwal","year":"2025","journal-title":"Nephrol Dial Transplant"},{"key":"2025122223464940200_bib12","doi-asserted-by":"publisher","first-page":"S239","DOI":"10.2337\/dc25-S011","article-title":"11. Chronic kidney disease and risk management: standards of care in diabetes-2025","volume":"48","author":"American Diabetes Association Professional Practice Committee","year":"2025","journal-title":"Diabetes Care"},{"key":"2025122223464940200_bib13","doi-asserted-by":"publisher","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"2025122223464940200_bib14","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1053\/j.ajkd.2010.02.344","article-title":"Modification of the CKD Epidemiology Collaboration (CKD-EPI) equation for Japanese: accuracy and use for population estimates","volume":"56","author":"Horio","year":"2010","journal-title":"Am J Kidney Dis"},{"key":"2025122223464940200_bib15","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/S2213-8587(18)30314-0","article-title":"Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials","volume":"7","author":"Heerspink","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2025122223464940200_bib16","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S2213-8587(18)30313-9","article-title":"Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies","volume":"7","author":"Coresh","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2025122223464940200_bib17","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1161\/CIRCULATIONAHA.121.057736","article-title":"Sodium-glucose cotransporter 2 inhibitors and risk of hyperkalemia in people with type 2 diabetes: a meta-analysis of individual participant data from randomized, controlled trials","volume":"145","author":"Neuen","year":"2022","journal-title":"Circulation"},{"key":"2025122223464940200_bib18","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1681\/ASN.2021070948","article-title":"Acute treatment effects on GFR in randomized clinical trials of kidney disease progression","volume":"33","author":"Neuen","year":"2022","journal-title":"J Am Soc Nephrol"},{"key":"2025122223464940200_bib19","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1001\/jama.2011.451","article-title":"A predictive model for progression of chronic kidney disease to kidney failure","volume":"305","author":"Tangri","year":"2011","journal-title":"JAMA"},{"key":"2025122223464940200_bib20","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.2337\/dc22-0698","article-title":"Development and validation of prediction models of adverse kidney outcomes in the population with and without diabetes","volume":"45","author":"Grams","year":"2022","journal-title":"Diabetes Care"},{"key":"2025122223464940200_bib21","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1016\/j.kint.2018.01.009","article-title":"Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate","volume":"93","author":"Grams","year":"2018","journal-title":"Kidney Int"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfaf160\/64167336\/gfaf160.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/41\/1\/161\/64167336\/gfaf160.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/41\/1\/161\/64167336\/gfaf160.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T04:46:51Z","timestamp":1766465211000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/41\/1\/161\/8244622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,31]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,8,31]]},"published-print":{"date-parts":[[2025,12,23]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfaf160","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,8,31]]}}}