{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:47:01Z","timestamp":1782107221509,"version":"3.54.5"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Drug\u2010induced kidney injury should be monitored throughout the drug development process to ensure patient safety. Standard kidney injury biomarkers may not always correlate with subtle microscopic histopathological kidney injury. Standard biomarkers are insufficiently sensitive for detection of early\u2010phase kidney injury. The need for more sensitive novel kidney injury biomarkers drove quantitative assessment of a panel of urine biomarkers, leading to US FDA qualification of a panel of six novel urine biomarkers for use in phase 1 clinical drug trials in healthy subjects. To qualify these biomarkers for use in the Japanese population, a multistep bridging strategy was developed to extrapolate US\u2010based evidence to Japan. We report the results of the Japanese healthy volunteer study, which was the first step of the clinical phase of the program in Japan. This was a nonintervention study designed to collect blood and urine samples from healthy Japanese subjects. The study design emulated the counterpart US study to facilitate comparisons. Forty subjects completed the Japan study. Geometric means of baseline values were within a twofold difference between the Japan and US studies for nearly all biomarkers. Intra\u2010subject variation was generally similar between the two studies. Application of the US\u2010based abnormality criteria to the Japan study gave satisfactory results with specificity above 0.85 for all biomarkers. This study generated well\u2010annotated biomarker samples in Japanese subjects, offering sufficient evidence to advance the project to the next stage of PMDA biomarker qualification.<\/jats:p>","DOI":"10.1111\/cts.70629","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:15:12Z","timestamp":1781090112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Urinary Kidney Injury Biomarker Profiles in Healthy Japanese Subjects With Reference to a Counterpart\n                    <scp>US<\/scp>\n                    Study"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6730-7873","authenticated-orcid":false,"given":"Takehiko","family":"Sambe","sequence":"first","affiliation":[{"name":"Showa Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1086-8746","authenticated-orcid":false,"given":"Takuya","family":"Mizukami","sequence":"additional","affiliation":[{"name":"Showa Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0063-2617","authenticated-orcid":false,"given":"Nicholas M. P.","family":"King","sequence":"additional","affiliation":[{"name":"Critical Path Institute  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1858-2655","authenticated-orcid":false,"given":"Gary","family":"Friedman","sequence":"additional","affiliation":[{"name":"Critical Path Institute  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9767-1481","authenticated-orcid":false,"given":"Stefan","family":"Sultana","sequence":"additional","affiliation":[{"name":"AstraZeneca Ltd.  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4285-4958","authenticated-orcid":false,"given":"Chieko","family":"Muto","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7210-8051","authenticated-orcid":false,"given":"Masanori","family":"Hizue","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6418-0547","authenticated-orcid":false,"given":"Yoichi","family":"Ii","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"US Food and Drug Administration (FDA) \u201cDDT\u2010BMQ\u2010000002 Safety Biomarker to be Used With Traditional Indicators to Indicate Renal Injury in Rat as Measured by Assay \u201dApplicant: Critical Path Institute Predictive Safety Testing Consortium 2008 https:\/\/force\u2010dsc.my.site.com\/ddt\/s\/ddt\u2010project?ddtprojectid=72."},{"key":"e_1_2_11_3_1","unstructured":"European Medicines Agency (EMA) \u201cFinal Conclusions on the Pilot Joint EMEA\/FDA VXDS Experience on Qualification of Nephrotoxicity Biomarkers \u201d2009 https:\/\/www.ema.europa.eu\/en\/documents\/regulatory\u2010procedural\u2010guideline\/final\u2010conclusions\u2010pilot\u2010joint\u2010european\u2010medicines\u2010agency\u2010food\u2010and\u2010drug\u2010administration\u2010vxds\u2010experience\u2010qualification\u2010nephrotoxicity\u2010biomarkers_en.pdf."},{"key":"e_1_2_11_4_1","unstructured":"Pharmaceutical and Medical Devices Agency (PMDA) \u201cRecord of the Consultation on Pharmacogenomics\/Biomarkers \u201dApplicant: Critical Path Institute Predictive Safety Testing Consortium 2010 https:\/\/www.pmda.go.jp\/files\/000160006.pdf."},{"key":"e_1_2_11_5_1","unstructured":"US Food and Drug Administration (FDA) \u201cSafety Biomarker Panel to Aid in the Detection of Kidney Tubular Injury in Phase 1 Trials in Healthy Volunteers \u201dApplicant: C\u2010Path Predictive Safety Testing Consortium 2018 https:\/\/force\u2010dsc.my.site.com\/ddt\/s\/ddt\u2010project?ddtprojectid=81."},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3531"},{"key":"e_1_2_11_7_1","unstructured":"Critical Path Institute PSTC Nephrotoxicity Working Group \u201cKidney Safety Biomarker Project Briefing Book for PMDA Consultation \u201dunpublished document 2018."},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.7143\/jhep.43.518"},{"key":"e_1_2_11_9_1","author":"Takahashi T.","year":"2015","journal-title":"Japan Health Insurance Association Annual Report"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.12.034"},{"key":"e_1_2_11_11_1","unstructured":"Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium Kidney Safety Biomarker Project Team Critical Path Institute's (C\u2010Path) Predictive Safety Testing Consortium Nephrotoxicity Working Group (FNIH BC\/PSTC NWG) \u201cUser's Guide: Kidney Safety Composite Measure Biomarker for Use in Clinical Development (Version 1.1) \u201d2019 https:\/\/c\u2010path.org\/wp\u2010content\/uploads\/2019\/05\/ksp\u2010compositecou\u2010userguide\u2010v1.1_20190515.pdf."},{"key":"e_1_2_11_12_1","unstructured":"Foundation for the National Institute of Health (FNIH) Biomarkers Consortium Kidney Safety Biomarkers Project Team and Critical Path Institute PSTC Nephrotoxicity Working Group \u201cKidney Safety Project Briefing Book: Project Update and Regulatory Agency Alignment \u201dunpublished document 2013."},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/26.4.404"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/1.2.124"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70629","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70629","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70629","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:48:32Z","timestamp":1782103712000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":13,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/cts.70629"],"URL":"https:\/\/doi.org\/10.1111\/cts.70629","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2026-01-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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