{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:00:21Z","timestamp":1784761221491,"version":"3.55.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2015,11,2]],"date-time":"2015-11-02T00:00:00Z","timestamp":1446422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg\u22121, i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-\u03b1 (GST-\u03b1), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/c5mb00492f","type":"journal-article","created":{"date-parts":[[2015,11,2]],"date-time":"2015-11-02T09:03:29Z","timestamp":1446455009000},"page":"133-144","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury"],"prefix":"10.1093","volume":"12","author":[{"given":"A Jin","family":"Won","sequence":"first","affiliation":[{"name":"College of Pharmacy, Pusan National University a , Busan, 609-735, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University b , Busan, 609-735, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Gyoon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Dankook University c , 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam, 330-714, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Bong","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Dankook University c , 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam, 330-714, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahn Soo","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Medicine, Konkuk University d , Chungju 380-701, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Kacew","sequence":"additional","affiliation":[{"name":"McLaughlin Centre for Population Health Risk Assessment, University of Ottawa e , Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University f , Suwon, 440-746, Republic of Korea \u00a0 hkims@skku.edu \u00a0 +82-31-292-8800 \u00a0 +82-31-290-7789"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee H","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Pusan National University a , Busan, 609-735, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Mu","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University f , Suwon, 440-746, Republic of Korea \u00a0 hkims@skku.edu \u00a0 +82-31-292-8800 \u00a0 +82-31-290-7789"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhkmann","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University b , Busan, 609-735, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Sik","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University f , Suwon, 440-746, Republic of Korea \u00a0 hkims@skku.edu \u00a0 +82-31-292-8800 \u00a0 +82-31-290-7789"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,11,2]]},"reference":[{"key":"2026010815191119700_cit1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.amjmed.2005.01.069","article-title":"Has mortality from acute renal failure decreased? 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