{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:04:42Z","timestamp":1791201882486,"version":"4.2.0"},"reference-count":36,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Intensive Care Med"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Positive fluid balance is associated with worse outcomes in sepsis-associated acute kidney injury (SA-AKI), but the optimal timing for active fluid removal (de-resuscitation) is unknown. We examined whether earlier loop-diuretic therapy is associated with lower mortality than later initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using MIMIC-IV v3.1, we performed a landmark-anchored cohort analysis informed by the target trial framework, with the 48-h landmark as time zero. Adults with Sepsis-3, Kidney Disease: Improving Global Outcomes (KDIGO) acute kidney injury within 48\u2005h, a positive 48-h fluid balance and no pre-landmark continuous renal replacement therapy were classified by the timing of the first loop diuretic as early (\u226424\u2005h after the landmark) or late (&gt;24\u2005h to 7 days). Outcomes were 28-day (primary), in-hospital and 90-day mortality. Stabilized inverse-probability-of-treatment weighting balanced nine covariates, and odds ratios (ORs) were estimated by weighted logistic regression, with sensitivity analyses,\n                      <jats:italic toggle=\"yes\">E<\/jats:italic>\n                      -values, subgroups and internal validation. External validation used the eICU Collaborative Research Database, with in-hospital mortality as the primary endpoint.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In MIMIC-IV (1419 early, 1924 late), early de-resuscitation was associated after weighting with lower 28-day mortality (19.9% vs 25.3%; OR, 0.731; 95% CI, 0.619-0.863;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.0002), in-hospital mortality (OR, 0.680; 95% CI, 0.570-0.811), and 90-day mortality (OR, 0.743; 95% CI, 0.640-0.862). In eICU (537 early, 1057 late), it was associated with lower in-hospital mortality (13.7% vs 18.3%; OR, 0.708; 95% CI, 0.541-0.928;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.013) and ICU mortality (OR, 0.663; 95% CI, 0.449-0.980). The association was directionally consistent across thresholds, complete-case and continuous-exposure analyses, subgroups, and bootstrap validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this observational analysis with external validation, earlier loop-diuretic de-resuscitation was associated with lower short-term mortality in SA-AKI with fluid accumulation. The findings are hypothesis-generating: a pragmatic randomized trial using the computable phenotype defined here is required to determine whether the association is causal.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/08850666261493365","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:51:47Z","timestamp":1790826707000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Timing of Loop Diuretic Initiation for De-Resuscitation in Sepsis-Associated Acute Kidney Injury: A Landmark Analysis with External Validation"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3546-0525","authenticated-orcid":false,"given":"Lujun","family":"Shao","sequence":"first","affiliation":[{"name":"The Affiliated Taizhou People's Hospital of Nanjing Medical University"},{"name":"Hirosaki University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0483-4789","authenticated-orcid":false,"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Taizhou People's Hospital of Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6005-1606","authenticated-orcid":false,"given":"Cheng","family":"Xu","sequence":"additional","affiliation":[{"name":"The Affiliated Taizhou People's Hospital of Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1275-1536","authenticated-orcid":false,"given":"Huiyu","family":"Tai","sequence":"additional","affiliation":[{"name":"The Affiliated Taizhou People's Hospital of Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0491-8731","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Taizhou People's Hospital of Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3143-565X","authenticated-orcid":false,"given":"Jinyu","family":"Shi","sequence":"additional","affiliation":[{"name":"The Affiliated Taizhou People's Hospital of Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-015-3934-7"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32563-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-024-05167-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.05.026"},{"key":"e_1_3_3_7_2","article-title":"Sepsis associated acute kidney injury","volume":"364","author":"Poston JT","year":"2019","unstructured":"Poston JT, Koyner JL. 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