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Normal healthy volunteers provided three morning spot urine collections over 4\u2009weeks. Patients undergoing surgical resection and intrathoracic cisplatin for malignant pleural mesothelioma provided urine samples pre\u2010 and postoperatively at 4, 8, and 12\u2009hours and daily for 6\u2009days. Using receiver\u2010operating characteristics curves, \u201cstatistically significant thresholds\u201d established peak longitudinal changes for 8 biomarkers to differentiate mesothelioma patients who developed acute kidney injury (AKI) from normal healthy volunteers. We also assessed \u201cmedically significant thresholds\u201d to differentiate mesothelioma patients who did vs. did not develop AKI. Statistically and medically significant thresholds for a fold\u2010change from baseline of urine creatinine (UCr)\u2010normalized values were established for 6 biomarkers: clusterin (2.2, 5.1); osteopontin (3.1, 7.1); <jats:italic>N<\/jats:italic>\u2010acetyl\u2010<jats:italic>\u00df<\/jats:italic>\u2010<jats:italic>D<\/jats:italic>\u2010glucosaminidase (2.7, 8.1); kidney injury molecule\u20101 (4.3, 7.5); cystatin C (1.8, 4.5); neutrophil gelatinase\u2010associated lipocalin (2.9, 7.8). For urine albumin and total protein, thresholds were established based on UCr\u2010normalized absolute values: (&gt;\u2009upper limit normal, &gt;\u200910\u00d7 upper limit normal). Statistically significant thresholds for all biomarkers outperformed eGFR at discriminating mesothelioma subjects exposed to cisplatin from healthy volunteers, demonstrating their utility for enhancing safe drug development. Medically significant thresholds provide perspective on when patients begin to exhibit AKI. These studies have established guideposts for confirmatory studies with additional cohorts and nephrotoxicants to formally qualify the selected biomarkers with worldwide regulatory authorities.<\/jats:p>","DOI":"10.1002\/cpt.3531","type":"journal-article","created":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T10:09:10Z","timestamp":1735985350000},"page":"1272-1283","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Urinary Kidney Injury Biomarker Profiles in Healthy Individuals and After Nephrotoxic and Ischemic Injury"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4004-326X","authenticated-orcid":false,"given":"Sushrut S.","family":"Waikar","sequence":"first","affiliation":[{"name":"Department of Medicine and Section of Nephrology Boston University Chobanian &amp; Avedisian School of Medicine and Boston Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5850-9083","authenticated-orcid":false,"given":"Robin","family":"Mogg","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  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