{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:55:26Z","timestamp":1792788926194,"version":"4.5.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","funder":[{"name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","award":["R01DK098234"],"award-info":[{"award-number":["R01DK098234"]}]},{"name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","award":["R01DK098234"],"award-info":[{"award-number":["R01DK098234"]}]},{"name":"U.S. Department of Veterans Affairs","award":["IK2 BX004986"],"award-info":[{"award-number":["IK2 BX004986"]}],"id":[{"id":"https:\/\/ror.org\/05rsv9s98","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","award":["2R01DK098234"],"award-info":[{"award-number":["2R01DK098234"]}]},{"name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","award":["2R01DK098234"],"award-info":[{"award-number":["2R01DK098234"]}]},{"name":"Norwegian Research Council","award":["295814"],"award-info":[{"award-number":["295814"]}]},{"name":"Norwegian Research Council","award":["295814"],"award-info":[{"award-number":["295814"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"abstract":"\n Key Points<\/jats:title>\n \n \n \n For the first time, we evaluated the association between kidney secretion and cardiovascular mortality in community-dwelling individuals.<\/jats:p>\n <\/jats:list-item>\n \n Worse tubular secretion was associated with a greater mortality risk, independent of eGFR, albuminuria, and other traditional risk factors.<\/jats:p>\n <\/jats:list-item>\n \n The association between worse tubular secretion and cardiovascular disease mortality was similar across major demographic categories.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Kidney tubular secretion is a critical mechanism for the clearance of numerous metabolites, toxins, and drugs. In populations with advanced CKD, low (worse) tubular secretion has been associated with an increased risk of cardiovascular disease (CVD). However, it remains unknown whether this relationship is also present in the general population.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this case\u2013cohort study, we selected a 10% random subcohort (\n n<\/jats:italic>\n =1246) from the Nord-Tr\u00f8ndelag Health Study-3 (a Norwegian community-dwelling population cohort) and we also sampled 141 CVD death cases that occurred outside of the subcohort. We developed a summary secretion score by averaging urine-to-plasma ratios of 12 endogenous secreted solutes, with lower ratios indicating worse tubular secretion. Weighted Cox proportional hazards models were used to assess the relationship between the summary secretion score and the risk of CVD mortality.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The mean (SD) age was 51 (14) years, 54.4% were female, 6% had prevalent CVD, and median (interquartile range) eGFR was 99 (90\u2013110) ml\/min per 1.73 m\n 2<\/jats:sup>\n at baseline. In multivariable models adjusted for demographics, CVD risk factors, eGFR, and albuminuria, each SD lower summary secretion score was associated with 27% higher risk of CVD mortality (95% confidence interval, 1.03 to 1.56). The results were similar across major demographic categories and among those with or without eGFR <60 ml\/min per 1.73 m\n 2<\/jats:sup>\n or albuminuria >30 mg\/g at baseline.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Among community-dwelling participants, lower tubular secretion is associated with increased CVD mortality independent of eGFR, albuminuria, and other CKD risk factors.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.0000001183","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:03:06Z","timestamp":1787241786000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Kidney Tubular Secretion Capacity and Risk of Cardiovascular Mortality in the General Population"],"prefix":"10.2215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6864-0336","authenticated-orcid":false,"given":"Alexander L.","family":"Bullen","sequence":"first","affiliation":[{"name":"Department of Medicine, Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California"},{"name":"Division of Nephrology and Hypertension, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-7469","authenticated-orcid":false,"given":"Ronit","family":"Katz","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-4208","authenticated-orcid":false,"given":"Simon B.","family":"Ascher","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kidney Health Research Collaborative, University of California, San Francisco, California"},{"name":"Division of Hospital Medicine, University of California Davis, Sacramento, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6016-4715","authenticated-orcid":false,"given":"Pranav S.","family":"Garimella","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0341-1190","authenticated-orcid":false,"given":"Yngvar","family":"Haaskjold","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway"},{"name":"Department of Nephrology, St Olav University Hospital, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius Altern","family":"\u00d8vrehus","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway"},{"name":"Department of Nephrology, St Olav University Hospital, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-204X","authenticated-orcid":false,"given":"Michael G.","family":"Shlipak","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kidney Health Research Collaborative, University of California, San Francisco, California"},{"name":"Department of Medicine, University of California San Francisco, San Francisco, California"},{"name":"San Francisco Veterans Affairs Health Care System, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-9869","authenticated-orcid":false,"given":"Joachim H.","family":"Ix","sequence":"additional","affiliation":[{"name":"Department of Medicine, Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California"},{"name":"Division of Nephrology and Hypertension, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9045-3569","authenticated-orcid":false,"given":"Stein Ivar","family":"Hallan","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway"},{"name":"Department of Nephrology, St Olav University Hospital, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"issue":"11","key":"B1-20261016","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.2215\/CJN.02440314","article-title":"Handling of drugs, metabolites, and uremic toxins by kidney proximal tubule drug transporters","volume":"10","author":"Nigam","year":"2015","journal-title":"Clin J Am Soc 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