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We leveraged real-world longitudinal data from the Stockholm CREAtinine Measurements (SCREAM) project to investigate trajectories linking PPI use with chronic kidney disease (CKD), CVAE, and all-cause mortality using a process mining approach. We identified 294,734 new users of PPIs or H2 blockers (H2Bs) with a baseline eGFR\u2009\u2265\u200960 mL\/min\/1.73\u00a0m\u00b2 and followed them for up to 15 years using a process-mining approach to discover disease trajectories. The association of PPI and CVAE is not significant after accounting for death as a competing event. However, PPI use is significantly associated with a higher subdistribution hazard of CKD and all-cause mortality compared to H2B. Our findings indicate that CKD may act as a mediator in the trajectory\n                    <jats:italic>PPI<\/jats:italic>\n                    \u2192\n                    <jats:italic>CKD<\/jats:italic>\n                    \u2192\n                    <jats:italic>CVAE<\/jats:italic>\n                    , underscore the importance of monitoring renal function in long-term PPI users, and emphasise the need for future prospective trials to clarify cardiovascular risks.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-23527-5","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T08:24:30Z","timestamp":1760343870000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Longitudinal trajectories unravel the complex interplay of medication, cardiovascular events, chronic kidney disease, and mortality"],"prefix":"10.1038","volume":"15","author":[{"given":"Kaile","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Abtahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Fernandez-Llatas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Seoane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"23527_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ejim.2019.11.017","volume":"72","author":"AA Manolis","year":"2020","unstructured":"Manolis, A. 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