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This mechanistic trial aimed to evaluate the effects of finerenone on vascular stiffness, as assessed using the cardio-ankle vascular index (CAVI), and cardiorenal biomarkers in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eligible patients with T2D and CKD (estimated glomerular filtration rate [eGFR], 25 to\u2009&lt;\u200990\u00a0mL\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      ; urinary albumin-to-creatinine ratio [UACR], 30 to\u2009&lt;\u20093500\u00a0mg\/g\u00a0Cr) were randomly allocated to receive either dose-adjusted finerenone or matching placebo. The primary endpoint was the change in CAVI at week 24. The key secondary endpoint was the proportional change in UACR from baseline over 24\u00a0weeks. As an exploratory analysis, changes in circulating proteins were measured by using the Olink\u00ae Target 96 Cardiovascular III and Inflammation panels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This investigator-initiated, multicentre, prospective, two-arm parallel, placebo-controlled, double-blind, randomised clinical trial was conducted at 13 sites in Japan. Among 102 patients randomised, 101 (66.3% men; median age, 73\u00a0years; eGFR, 56.2\u00a0mL\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      ; and UACR, 193.8\u00a0mg\/g\u00a0Cr) were analysed. Changes in CAVI at week 24 were\u2009\u2212\u20090.023 (95% confidence interval [CI],\u2009\u2212\u20090.299 to 0.254) for finerenone and 0.011 (95% CI,\u2009\u2212\u20090.245 to 0.267) for placebo. The group difference was\u2009\u2212\u20090.057 (95% CI,\u2009\u2212\u20090.428 to 0.314;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.760). Compared with placebo, finerenone led to a 29% reduction in UACR levels at weeks 12 (group ratio 0.706 [95% CI, 0.504 to 0.989;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.043]) and 24 (0.709 [95% CI, 0.506 to 0.994;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.046]). Finerenone also resulted in an early and sustained eGFR decline over 24\u00a0weeks, without increasing levels of urinary biomarkers of acute tubular injury. Finerenone, compared with placebo, was associated with nominal changes in the expression of 11 proteins among the 181 circulating proteins tested.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Finerenone did not affect changes in vascular stiffness but led to a significant and sustained reduction in albuminuria in patients with T2D and CKD. The clinical benefits of finerenone may result from lowering intraglomerular pressure rather than from its effect on vascular stiffness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>ClinicalTrial.gov (NCT05887817) and Japan Registry of Clinical Trials (jRCTs021230011).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                    <jats:p>This mechanistic clinical trial involving patients with T2D and CKD found that 24-week finerenone therapy did not significantly reduce CAVI from baseline compared with placebo (\u22120.057; 95% CI, \u22120.428 to 0.314), led to a 29% reduction (group ratio [finerenone vs. placebo] of 0.71) in UACR levels, and was associated with nominal changes in 11 circulating proteins (six upregulated and five downregulated) over 24 weeks. CAVI, cardio-ankle vascular index; CI, confidence interval; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; T2D, type 2 diabetes; UACR, urinary albumin-to-creatinine ratio.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-025-03014-x","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T14:26:18Z","timestamp":1764944778000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Effects of finerenone on arterial stiffness and cardiorenal biomarkers in patients with type 2 diabetes and chronic kidney disease: a randomised placebo-controlled mechanistic trial 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F2023001), and the trial adhered to the principles of the Declaration of Helsinki and the Clinical Trial Act in Japan. Written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"A.T. has received honoraria from Boehringer Ingelheim Japan, Mochida, and Amgen and research funding from Bristol Myers Squibb; A.T. is an Editorial Board member of the journal and not involved in handling this manuscript during the submission and review processes. M.V. has received research grant support, served on advisory boards or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi and Tricog Health and participates on clinical trial committees for studies sponsored by Amgen, AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech and Impulse Dynamics. T.I. has received lecture fees from Kyowa Kirin and Eizai Pharmaceutical and has served as a statistician in the Organization for Clinical Medicine Promotion. S.Suwa. has received honoraria from Abbott Medical Japan and Daiichi Sankyo. H.T. has received honoraria from Abbott Medical Japan, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kowa, Medtronic, and Nihon Medi-Physics. M.Miyazono. has received honoraria from Chugai Pharmaceutical, Astellas, Kyowa Kirin, Mitsubishi Tanabe, Mochida Pharmaceutical, AstraZeneca, Bayer Yakuhin, Torii Pharmaceutical, Fuso Pharmaceutical Industries, Daiichi Sankyo Company, Limited, Teijin Pharma, Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd., and Kissei Pharmaceutical; research funding from Chugai Pharmaceutical and Kyowa Kirin; and scholarships from Kyowa Kirin, Torii Pharmaceutical, Fuso Pharmaceutical Industries, and Kissei Pharmaceutical. N.T. received honoraria from Daiichi Sankyo, Novartis Pharma, Bristol Myers Squibb, Pfizer, Otsuka Pharmaceutical, Medtronic, Toa Eiyo, and Nippon Boehringer-Ingelheim. M.S. has received honoraria from Bayer Yakuhin, Ltd. MMoroi has received honoraria from Sanofi, Amicus Therapeutics, Takeda, Otsuka, Kowa, Mitsubishi Tanabe Pharma, Daiichi Sankyo, Astra Zeneca, Nihon Medi-physics, and Bayer and research funding from Taisho Pharmaceutical. K.K. received honorariums from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bayer Yakuhin, Ltd., Otsuka Pharmaceutical Co., Ltd., and Novartis Pharmaceuticals Co., Ltd. D.F. received research funding from AMGEN Inc. and BIOTRONIK Japan, Inc.; honoraria from Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., and Kowa Company, Ltd. K.Tanabe. has received honoraria from Kowa, Boehringer-Ingelheim, Daiichi Sankyo, Toa Eiyo, Eli Lilly, Novartis, Novo Nordisk, Bayer, Pfizer, AstraZeneca, Ono pharma, Otsuka, and Takeda. Y.Horiuchi. has received honoraria from Bayer Pharmaceuticals and research funding from Asahi Intecc. H.Y. has received outsourcing fees from the organization for Clinical Medicine Promotion. T.M. has received honoraria from Kowa, Novartis Japan and AstraZeneca and research funding from Kowa. M.N. has received honoraria and advisory fees from Boehringer Ingelheim, Kyowa Kirin, Astellas, Astra Zeneca, GSK, Daiichi Sankyo, Tanabe-Mitsubishi, Chugai, Torii, JT, and Novo Nordisk and research funding from Kyowa-Kirin, Daiichi Sankyo, Astellas, Ono, Tanabe-Mitsubishi, JT, Chugai, Bayer, Torii, and Takeda. H.S. has received honoraria from Bayer and Daiichi Sankyo, Japan. K.N. has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim Japan, Daiichi Sankyo, Kowa, Mochida, MSD, Novartis, Novo Nordisk, and Otsuka; research grants from Astellas, Bayer, \u00f0Fujiyakuhin, Mochida, Novartis; scholarship from Abbott, Boehringer Ingelheim Japan, and Teijin. All other authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"454"}}