{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T09:40:36Z","timestamp":1792402836129,"version":"4.4.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Urinary TIMP-2 (tissue inhibitor of metalloproteinases-2) and IGFBP7 (insulin-like growth factor\u2013binding protein 7) can predict acute kidney injury (AKI) in patients with sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To address critical questions about whether biomarkers can inform the response to treatment and whether they might be used to guide therapy, as most sepsis patients present with AKI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured [TIMP-2]\u2009\u00b7\u2009[IGFBP7] before and after a 6-hour resuscitation in 688 patients with septic shock enrolled in the ProCESS (Protocol-based Care for Early Septic Shock) trial. Our primary endpoint was stage 3 AKI, renal replacement therapy, or death within 7 days.<\/jats:p>\n                    <jats:p>Measurements and Main Results: The endpoint was reached in 113 patients (16.4%). In patients with negative [TIMP-2]\u2009\u00b7\u2009[IGFBP7] at baseline, those who became positive (&amp;gt;0.3 U) after resuscitation had three-times higher risk compared with those who remained negative (21.8% vs. 8.5%; P\u2009=\u20090.01; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.31\u20136.87). Conversely, compared with patients with a positive biomarker at baseline that were still positive at Hour 6, risk was reduced for patients who became negative (23.8% vs. 9.8%; P\u2009=\u20090.01; OR, 2.15; 95% CI, 1.17\u20133.95). A positive [TIMP-2]\u2009\u00b7\u2009[IGFBP7] after resuscitation was associated with worse outcomes in both patients with and without AKI at that time point. The clinical response to resuscitation, as judged by the Acute Physiology and Chronic Health Evaluation II score, was weakly predictive of the endpoint (area under the curve, 0.68; 95% CI, 0.62\u20130.73) and improved with addition of [TIMP-2]\u2009\u00b7\u2009[IGFBP7] (0.72; 95% CI, 0.66\u20130.77; P\u2009=\u20090.03). Different resuscitation protocols did not alter biomarker trajectories, nor did they alter outcomes in biomarker-positive or biomarker-negative patients. However, biomarker trajectories were associated with outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Changes in urinary [TIMP-2]\u2009\u00b7\u2009[IGFBP7] after initial fluid resuscitation identify patients with sepsis who have differing risk for progression of AKI.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT 00510835).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201906-1197oc","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T13:37:41Z","timestamp":1593092261000},"page":"1262-1270","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":72,"title":["Serial Measurement of Cell-Cycle Arrest Biomarkers [TIMP-2]\u2009\u00b7\u2009[IGFBP7] and Risk for Progression to Death, Dialysis, or Severe Acute Kidney Injury in Patients with Septic Shock"],"prefix":"10.1093","volume":"202","author":[{"given":"Marco","family":"Fiorentino","sequence":"first","affiliation":[{"name":"Center for Critical Care Nephrology and"},{"name":"Clinical Research, Investigation and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongying","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Critical Care Nephrology and"},{"name":"Graduate School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Critical Care Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Singbartl","sequence":"additional","affiliation":[{"name":"Center for Critical Care Nephrology and"},{"name":"Renal-Electrolyte Division, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Palevsky","sequence":"additional","affiliation":[{"name":"Center for Critical Care Nephrology and"},{"name":"Department of Emergency Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakhmir S.","family":"Chawla","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Mayo Clinic, Phoenix, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Huang","sequence":"additional","affiliation":[{"name":"Renal Section, Medical Service, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; 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