{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T07:56:59Z","timestamp":1776412619904,"version":"3.51.2"},"reference-count":28,"publisher":"S. Karger AG","issue":"12","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"published-print":{"date-parts":[[2021]]},"abstract":"<jats:p>Introduction: Worsening kidney function (WKF) is frequent among patients with type 2 diabetes (T2D) and a recent acute coronary syndrome (ACS) and is associated with a poor prognosis. An accurate prediction of WKF is clinically important. Aims: Using data from the Cardiovascular Outcomes Study of Alogliptin in Patients with Type 2 Diabetes and Acute Coronary Syndrome trial including patients with T2D and a recent ACS, and a large biomarker panel incorporating proteins measured both in blood and urine, we aim to determine those with best performance for WKF prediction. Methods: WKF was defined as a \u226540% estimated glomerular filtration rate (eGFR) drop from baseline, eGFR &lt;15 mL\/min, or dialysis. Mixed-effects and time-updated Cox models were used. Results: 5,131 patients were included from whom 222 (4.3%) developed at least one WKF episode over a median follow-up of 18 months. Patients who developed WKF were more frequently women, had longer diabetes duration, a more frequent heart failure history, higher anemia prevalence, and impaired kidney function. In multivariable models including all variables (clinical and biomarkers) independently associated with WKF with a p value \u22640.0001, blood kidney injury molecule 1 (KIM-1) was (by far) the variable with strongest WKF association, followed by anemia. KIM-1 alone provided good discrimination for WKF prediction (area under the curve = 0.73). Patients in the high KIM-1-derived risk tertile had a 6.7-fold higher risk of any WKF than patients classified as low risk. In time-updated Cox models, the occurrence of WKF was independently associated with a higher risk of death: adjusted hazard ratio = 4.93 (3.06\u20137.96), p value &lt;0.0001. Conclusion: Blood KIM-1 was the biomarker with the strongest association with WKF. The occurrence of WKF was independently associated with a higher risk of subsequent cardiovascular events and mortality. <\/jats:p>","DOI":"10.1159\/000519436","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T22:00:45Z","timestamp":1638828045000},"page":"969-976","source":"Crossref","is-referenced-by-count":7,"title":["Blood and Urine Biomarkers Predicting Worsening Kidney Function in Patients with Type 2 Diabetes Post-Acute Coronary Syndrome: An Analysis from the EXAMINE Trial"],"prefix":"10.1159","volume":"52","author":[{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[]},{"given":"George","family":"Bakris","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0724-3104","authenticated-orcid":false,"given":"Cyrus","family":"Mehta","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8936-967X","authenticated-orcid":false,"given":"William B.","family":"White","sequence":"additional","affiliation":[]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[]}],"member":"127","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199910073411506"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-2209"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1916393"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013070758"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.7326\/M18-1037"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32563-2"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03520807"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2018.10.035"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.19209"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32590-X"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305889"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2011.08.004"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0731-2"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3389-3"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.201"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.2"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23056"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.02.003"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.10971012"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1186\/cc12503"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.7.4135"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00631.x"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.314"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfy382"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.426"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05280517"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfz294"}],"container-title":["American Journal of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/ajn\/article-pdf\/52\/12\/969\/3909490\/000519436.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/ajn\/article-pdf\/52\/12\/969\/3909490\/000519436.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:25:32Z","timestamp":1745421932000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000519436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"references-count":28,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,1,13]]},"published-print":{"date-parts":[[2022,1,18]]}},"URL":"https:\/\/doi.org\/10.1159\/000519436","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.17128805","asserted-by":"subject"}]},"ISSN":["0250-8095","1421-9670"],"issn-type":[{"value":"0250-8095","type":"print"},{"value":"1421-9670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021]]}}}