{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:53:22Z","timestamp":1785549202499,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["DT15S\/00166, PI10-00624, PI15\/01055, PI18\/00996 and Retic RD016\/0009\/0025"],"award-info":[{"award-number":["DT15S\/00166, PI10-00624, PI15\/01055, PI18\/00996 and Retic RD016\/0009\/0025"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008431","name":"Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["IES160P20"],"award-info":[{"award-number":["IES160P20"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FEDER"],"award-info":[{"award-number":["FEDER"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nephrotoxicity is a major cause of intrinsic acute kidney injury (AKI). Because renal tissue damage may occur independently of a reduction in glomerular filtration rate and of elevations in plasma creatinine concentration, so-called injury biomarkers have been proposed to form part of diagnostic criteria as reflective of tubular damage independently of renal function status. We studied whether the urinary level of NGAL, KIM-1, GM2AP, t-gelsolin, and REGIIIb informed on the extent of tubular damage in rat models of nephrotoxicity, regardless of the etiology, moment of observation, and underlying pathophysiology. At a time of overt AKI, urinary biomarkers were measured by Western blot or ELISA, and tubular necrosis was scored from histological specimens stained with hematoxylin and eosin. Correlation and regression studies revealed that only weak relations existed between biomarkers and tubular damage. Due to high interindividual variability in the extent of damage for any given biomarker level, urinary injury biomarkers did not necessarily reflect the extent of the underlying tissue injury in individual rats. We contended, in this work, that further pathophysiological contextualization is necessary to understand the diagnostic significance of injury biomarkers before they can be used for renal tubular damage severity stratification in the context of nephrotoxic and, in general, intrinsic AKI.<\/jats:p>","DOI":"10.3390\/ijms23073494","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T12:20:25Z","timestamp":1648038025000},"page":"3494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Urinary Level of Injury Biomarkers Is Not Univocally Reflective of the Extent of Toxic Renal Tubular Injury in Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"Sandra M.","family":"Sancho-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Universidad de Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain"},{"name":"National Network for Kidney Research REDINREN, RD016\/0009\/0025, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8719-7165","authenticated-orcid":false,"given":"Mar\u00eda","family":"Herrero","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Universidad de Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1232-3221","authenticated-orcid":false,"given":"Miguel","family":"Fontecha-Barriuso","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Universidad de Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4241-2559","authenticated-orcid":false,"given":"Joana","family":"Mercado-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Universidad de Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7778-7495","authenticated-orcid":false,"given":"Francisco J.","family":"L\u00f3pez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Universidad de Salamanca (USAL), 37007 Salamanca, Spain"},{"name":"Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain"},{"name":"National Network for Kidney Research REDINREN, RD016\/0009\/0025, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Fundaci\u00f3n Instituto de Estudios de Ciencias de la Salud de Castilla y Le\u00f3n (IECSCYL), 42002 Soria, Spain"},{"name":"Group of Biomedical Research on Critical Care (BioCritic), 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/ki.2014.328","article-title":"The definition of acute kidney injury and its use in practice","volume":"87","author":"Thomas","year":"2015","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0272-6386(12)81128-0","article-title":"Community-Acquired Acute Renal Failure","volume":"17","author":"Kaufman","year":"1991","journal-title":"Am. 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