{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:49:19Z","timestamp":1789080559282,"version":"build-2803163510"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"DOI":"10.13039\/100009012","name":"Veterans Affairs San Diego Healthcare System","doi-asserted-by":"publisher","award":["5IK2BX004986"],"award-info":[{"award-number":["5IK2BX004986"]}],"id":[{"id":"10.13039\/100009012","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K24DK110427"],"award-info":[{"award-number":["K24DK110427"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["5R01DK098234"],"award-info":[{"award-number":["5R01DK098234"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["14EIA18560026"],"award-info":[{"award-number":["14EIA18560026"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Kidney tubular secretion is an essential mechanism for clearing many common antihypertensive drugs and other metabolites and toxins. It is unknown whether novel measures of tubular secretion are associated with adverse events (AEs) during hypertension treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Among 2089 SPRINT (Systolic Blood Pressure Intervention Trial) participants with baseline eGFR &lt;60 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      , we created a summary secretion score by averaging across the standardized spot urine-to-plasma ratios of ten novel endogenous tubular secretion measures, with lower urine-to-plasma ratios reflecting worse tubular secretion. Multivariable Cox proportional hazards models were used to evaluate associations between the secretion score and risk of a composite of prespecified serious AEs (hypotension, syncope, bradycardia, AKI, electrolyte abnormalities, and injurious falls). The follow-up protocol for SPRINT routinely assessed two laboratory monitoring AEs (hyperkalemia and hypokalemia).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 30% of participants experienced at least one AE during a median follow-up of 3.0 years. In multivariable models adjusted for eGFR and albuminuria, lower (worse) secretion scores at baseline were associated with greater risk of the composite AE outcome (hazard ratio per 1-SD lower secretion score, 1.16; 95% confidence interval, 1.04 to 1.27). In analyses of the individual AEs, lower secretion score was associated with significantly greater risk of AKI, serious electrolyte abnormalities, and ambulatory hyperkalemia. Associations were similar across randomized treatment assignment groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Among SPRINT participants with CKD, worse tubular secretion was associated with greater risk of AEs, independent of eGFR and albuminuria.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2022010117","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T12:00:13Z","timestamp":1660651213000},"page":"1915-1926","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":16,"title":["Markers of Kidney Tubular Secretion and Risk of Adverse Events in SPRINT Participants with CKD"],"prefix":"10.1681","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6864-0336","authenticated-orcid":false,"given":"Alexander L.","family":"Bullen","sequence":"first","affiliation":[{"name":"Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California"},{"name":"Division of Nephrology-Hypertension, University of California, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9031-9327","authenticated-orcid":false,"given":"Simon B.","family":"Ascher","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, California"},{"name":"Division of Hospital Medicine, University of California Davis, Sacramento, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Scherzer","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, 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-Hypertension, University of California, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronit","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stein I.","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"}]},{"given":"Alfred K.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, University of Utah Health, Salt Lake City, Utah"},{"name":"Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1378-2609","authenticated-orcid":false,"given":"Kalani L.","family":"Raphael","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University and VA Portland Health Care System, Portland, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"Estrella","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasantha K.","family":"Jotwani","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4352-2103","authenticated-orcid":false,"given":"Rakesh","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, University of California, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse C.","family":"Seegmiller","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Shlipak","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim H.","family":"Ix","sequence":"additional","affiliation":[{"name":"Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California"},{"name":"Division of Nephrology-Hypertension, University of California, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,10]]},"reference":[{"key":"B1-20250823","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1001\/jama.2016.19043","article-title":"Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 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