{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:53:31Z","timestamp":1792788811030,"version":"4.5.0"},"reference-count":20,"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":"Bayer AG"}],"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 We investigated the effect of empagliflozin, finerenone, and their combination on eGFR decline in people with type 2 diabetes and albuminuria.<\/jats:p>\n <\/jats:list-item>\n \n Acute declines in eGFR occurred more in those on combination therapy, on diuretics, and with higher eGFR; eGFR changes were reversible.<\/jats:p>\n <\/jats:list-item>\n \n Finerenone's additive effect to empagliflozin on urinary albumin-to-creatinine ratio lowering was nonhemodynamic; empagliflozin lowered urinary albumin-to-creatinine ratio in part driven by eGFR change.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n eGFR decline is common with sodium-glucose cotransporter 2 inhibitors and renin\u2013angiotensin system inhibitors, often prompting treatment interruption or cessation, limiting cardiorenal benefits. This mostly prespecified COmbinatioN effect of FInerenone anD EmpaglifloziN in Participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint (CONFIDENCE) trial analysis investigated the effect of empagliflozin, finerenone, and their combination on change from baseline in eGFR and its determinants and the relationship of change in eGFR with albuminuria reduction in people with type 2 diabetes and CKD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Evaluable participants (\n N<\/jats:italic>\n =790) with type 2 diabetes, CKD, and albuminuria, receiving stable doses of renin\u2013angiotensin system inhibitors, were randomized 1:1:1 to empagliflozin, finerenone, or both. The primary outcome was urinary albumin-to-creatinine ratio (UACR) change from baseline to day 180. We assessed mean eGFR change from baseline at day 14 (acute), determinants of acute eGFR decline, and acute eGFR change from baseline as a mediator of UACR reduction at day 180.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The mean acute eGFR decline was greater with combination therapy (\u22126.6 ml\/min per 1.73 m\n 2<\/jats:sup>\n ) than with finerenone (\u22122.1 ml\/min per 1.73 m\n 2<\/jats:sup>\n ) or empagliflozin (\u22124.8 ml\/min per 1.73 m\n 2<\/jats:sup>\n ) monotherapy;\n P<\/jats:italic>\n < 0.001. Acute decline in eGFR was significantly more pronounced among participants with higher baseline eGFR and in those receiving diuretics at baseline (\n P<\/jats:italic>\n < 0.001 for both factors). Baseline values for systolic BP and UACR had no statistically significant effect on acute eGFR decline. Exploratory analysis showed that acute eGFR change mediated 28% of the effect of adding empagliflozin to finerenone on UACR reduction at day 180 but only 5.2% of the effect when adding finerenone to empagliflozin. AKI was uncommon in all treatment groups.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Acute eGFR decline was significantly associated with combination therapy, higher baseline eGFR, and diuretic use at baseline.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n ClinicalTrials.gov, NCT05254002.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001071","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T02:00:06Z","timestamp":1774836006000},"page":"1969-1978","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Acute eGFR Changes and Their Mediation of Albuminuria Reduction with Empagliflozin and Finerenone"],"prefix":"10.1681","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-7100","authenticated-orcid":false,"given":"Rajiv","family":"Agarwal","sequence":"first","affiliation":[{"name":"Division of Nephrology, Richard L. Roudebush VA Medical Center, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Correa-Rotter","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Mineral Metabolism, National Medical Science and Nutrition Institute Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sankar D.","family":"Navaneethan","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Fukami","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan"}],"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":"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\/0000-0002-3154-5332","authenticated-orcid":false,"given":"Johannes F.E.","family":"Mann","sequence":"additional","affiliation":[{"name":"KfH Kidney Centre, Munich, Germany"},{"name":"Department of Nephrology and Hypertension, Friedrich Alexander University, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6228-6521","authenticated-orcid":false,"given":"Janet B.","family":"McGill","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Lipid Research, School of Medicine, Washington University in St. Louis, St. Louis, Missouri"}],"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 Kidney Center, UNC School of Medicine, Chapel Hill, North Carolina"}],"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, 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":"University of Texas Southwestern Medical Center, Dallas, Texas"}],"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, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0885-1953","authenticated-orcid":false,"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2816-4889","authenticated-orcid":false,"given":"Charlie","family":"Scott","sequence":"additional","affiliation":[{"name":"Clinical Statistics and Analytics, Bayer US LLC, Whippany, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Global Medical Evidence, Bayer AG, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8334-4311","authenticated-orcid":false,"given":"Carolina","family":"Aldworth","sequence":"additional","affiliation":[{"name":"US Medical Affairs, Bayer US LLC, Whippany, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9967-5352","authenticated-orcid":false,"given":"Jennifer B.","family":"Green","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8820-5702","authenticated-orcid":false,"given":"Matthew R.","family":"Weir","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"issue":"24","key":"B1-20261023","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N Engl J Med"},{"issue":"15","key":"B2-20261023","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1056\/NEJMoa2024816","article-title":"Dapagliflozin in patients with chronic kidney disease","volume":"383","author":"Heerspink","year":"2020","journal-title":"N Engl J Med"},{"issue":"2","key":"B3-20261023","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa2204233","article-title":"Empagliflozin in patients with chronic kidney disease","volume":"388","author":"Herrington","year":"2023","journal-title":"N Engl J Med"},{"issue":"23","key":"B4-20261023","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1056\/NEJMoa2025845","article-title":"Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes","volume":"383","author":"Bakris","year":"2020","journal-title":"N Engl J Med"},{"issue":"24","key":"B5-20261023","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1056\/NEJMoa2110956","article-title":"Cardiovascular events with finerenone in kidney disease and type 2 diabetes","volume":"385","author":"Pitt","year":"2021","journal-title":"N Engl J Med"},{"issue":"2","key":"B6-20261023","doi-asserted-by":"crossref","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"},{"issue":"6","key":"B7-20261023","doi-asserted-by":"crossref","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"},{"issue":"4S","key":"B8-20261023","first-page":"S117","article-title":"KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","year":"2024","journal-title":"Kidney Int"},{"issue":"5","key":"B9-20261023","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1001\/jamainternmed.2020.0193","article-title":"Association between renin-angiotensin system blockade discontinuation and all-cause mortality among persons with low estimated glomerular filtration rate","volume":"180","author":"Qiao","year":"2020","journal-title":"JAMA Intern Med"},{"issue":"4","key":"B10-20261023","doi-asserted-by":"crossref","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"},{"issue":"8","key":"B11-20261023","doi-asserted-by":"crossref","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"},{"issue":"5","key":"B12-20261023","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1159\/000131102","article-title":"Analyzing change: a primer on multilevel models with applications to nephrology","volume":"28","author":"Holden","year":"2008","journal-title":"Am J Nephrol"},{"issue":"11","key":"B13-20261023","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1001\/jama.2021.14075","article-title":"A guideline for reporting mediation analyses of randomized trials and observational studies: the AGReMA statement","volume":"326","author":"Lee","year":"2021","journal-title":"JAMA"},{"issue":"2","key":"B14-20261023","doi-asserted-by":"crossref","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"},{"issue":"6","key":"B16-20261023","doi-asserted-by":"crossref","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"},{"issue":"1","key":"B17-20261023","doi-asserted-by":"crossref","first-page":"R75","DOI":"10.1152\/ajpregu.00357.2011","article-title":"Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat","volume":"302","author":"Thomson","year":"2012","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"2","key":"B18-20261023","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1053\/j.ajkd.2024.08.003","article-title":"KDOQI US commentary on the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD","volume":"85","author":"Navaneethan","year":"2025","journal-title":"Am J Kidney Dis"},{"issue":"18","key":"B19-20261023","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.jacc.2025.05.007","article-title":"2025 AHA\/ACC\/AANP\/AAPA\/ABC\/ACCP\/ACPM\/AGS\/AMA\/ASPC\/NMA\/PCNA\/SGIM guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"86","author":"Jones","year":"2025","journal-title":"J Am Coll Cardiol"},{"issue":"10523","key":"B20-20261023","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/S0140-6736(25)01942-7","article-title":"Chronic kidney disease","volume":"407","author":"Herrington","year":"2026","journal-title":"Lancet"},{"issue":"2","key":"B21-20261023","doi-asserted-by":"crossref","first-page":"F156","DOI":"10.1152\/ajprenal.00409.2012","article-title":"Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus","volume":"304","author":"Vallon","year":"2013","journal-title":"Am J Physiol Renal Physiol"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:01:16Z","timestamp":1792771276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,29]]},"references-count":20,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.0000001071","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":"2026-01-14","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-03","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}