{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:29:20Z","timestamp":1793395760197,"version":"4.5.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Hyperkalemia is common after treatment with a mineralocorticoid receptor antagonist (MRA). In the FIDELIO-DKD randomized trial, the nonsteroidal MRA finerenone improved cardiorenal outcomes, but was associated with a twofold higher risk of hyperkalemia versus placebo, consistent across patient subgroups. Short-term increases in serum potassium and decreases in eGFR with finerenone or placebo were associated with subsequent hyperkalemia; at month 4, the magnitude of the increased hyperkalemia risk for any given change from baseline was smaller with finerenone than with placebo. Routine potassium monitoring, with temporary treatment interruption and dose reduction in the event of hyperkalemia, is necessary for the safe use of finerenone to protect the kidneys and cardiovascular system of patients with CKD and T2D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Finerenone reduced risk of cardiorenal outcomes in patients with CKD and type 2 diabetes in the FIDELIO-DKD trial. We report incidences and risk factors for hyperkalemia with finerenone and placebo in FIDELIO-DKD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This\n                      <jats:italic toggle=\"yes\">post hoc<\/jats:italic>\n                      safety analysis defined hyperkalemia as \u2265mild or \u2265moderate based on serum potassium concentrations of &gt;5.5 or &gt;6.0 mmol\/L, respectively, assessed at all regular visits. Cumulative incidences of hyperkalemia were based on the Aalen\u2013Johansen estimator using death as competing risk. A multivariate Cox proportional hazards model identified significant independent predictors of hyperkalemia. Restricted cubic splines assessed relationships between short-term post-baseline changes in serum potassium or eGFR and subsequent hyperkalemia risk. During the study, serum potassium levels guided drug dosing. Patients in either group who experienced \u2265mild hyperkalemia had the study drug withheld until serum potassium was \u22645.0 mmol\/L; then the drug was restarted at the 10 mg daily dose. Placebo-treated patients underwent sham treatment interruption and downtitration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Over 2.6 years\u2019 median follow-up, 597 of 2785 (21.4%) and 256 of 2775 (9.2%) patients treated with finerenone and placebo, respectively, experienced treatment-emergent \u2265mild hyperkalemia; 126 of 2802 (4.5%) and 38 of 2796 (1.4%) patients, respectively, experienced moderate hyperkalemia. Independent risk factors for \u2265mild hyperkalemia were higher serum potassium, lower eGFR, increased urine albumin-creatinine ratio, younger age, female sex,\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -blocker use, and finerenone assignment. Diuretic or sodium-glucose cotransporter\u20132 inhibitor use reduced risk. In both groups, short-term increases in serum potassium and decreases in eGFR were associated with subsequent hyperkalemia. At month 4, the magnitude of increased hyperkalemia risk for any change from baseline was smaller with finerenone than with placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Finerenone was independently associated with hyperkalemia. However, routine potassium monitoring and hyperkalemia management strategies employed in FIDELIO-DKD minimized the impact of hyperkalemia, providing a basis for clinical use of finerenone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2021070942","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T13:55:21Z","timestamp":1635947721000},"page":"225-237","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":262,"title":["Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial"],"prefix":"10.1681","volume":"33","clinical-trial-number":[{"clinical-trial-number":"nct02540993","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-7100","authenticated-orcid":false,"given":"Rajiv","family":"Agarwal","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Richard L. Roudebush Veterans Affairs Medical Center and Indiana University, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer","family":"Joseph","sequence":"additional","affiliation":[{"name":"Cardiology and Nephrology Clinical Development, Bayer AG, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (Campus Virchow-Klinikum) and Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research Partner Site Berlin, Charit\u00e9 Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens, School of Medicine, Department of Cardiology, Attikon University Hospital, Athens, Greece"}],"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, Gentofte, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6278-7951","authenticated-orcid":false,"given":"Luis M.","family":"Ruilope","sequence":"additional","affiliation":[{"name":"Cardiorenal Translational Laboratory and Hypertension Unit, Institute of Research imas12, Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dia en Red Enfermedades Cardiovasculares (CIBER-CV), Hospital Universitario 12 de Octubre, Madrid, Spain"},{"name":"Faculty of Sport Sciences, European University of Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kolkhof","sequence":"additional","affiliation":[{"name":"Research and Development, Preclinical Research Cardiovascular, Bayer AG, Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Scott","sequence":"additional","affiliation":[{"name":"Data Science and Analytics, Bayer PLC, Reading, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lawatscheck","sequence":"additional","affiliation":[{"name":"Medical Affairs & Pharmacovigilance, Pharmaceuticals, Bayer AG, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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