{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:11:46Z","timestamp":1773195106880,"version":"3.50.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>Acute kidney injury (AKI) is associated with increased morbidity and mortality and may develop secondary to systemic inflammatory conditions. Conventional biomarkers, such as serum creatinine and urinary gamma-glutamyl transferase (GGT), often fail to detect early renal injury. Cell cycle arrest biomarkers, including tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), have shown potential for early AKI detection in critically ill human patients; however, evidence in veterinary medicine remains limited. This prospective cross-sectional blinded study evaluated whether urinary TIMP-2 and IGFBP7 reflect histopathological renal injury severity in 27 clinically non-azotemic female dogs with pyometra and systemic inflammatory response syndrome (SIRS). Renal tissue samples were collected during ovariohysterectomy and graded according to tubular, glomerular and interstitial lesions. Animals were categorized as having discrete, moderate or severe injury based on cumulative lesion scores. Urinary TIMP-2 and IGFBP7, either alone or normalized to urinary creatinine, were compared with serum creatinine, symmetric dimethylarginine (SDMA) and protein-to-creatinine ratio (UPC). All dogs were non-azotemic at presentation. Tubular injury was the most prevalent histopathological finding. Conventional biomarkers did not differentiate lesion severity, whereas urinary TIMP-2 and IGFBP7 showed a significant association with increasing renal injury grade. Principal component analysis supported these findings. These results suggest that urinary TIMP-2 and IGFBP7 can detect renal lesions before azotemia and may serve as promising biomarkers for the identification of pre-azotemic renal injury in dogs with pyometra.<\/jats:p>","DOI":"10.3389\/fvets.2026.1788906","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:31:05Z","timestamp":1773120665000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Urinary cell cycle arrest biomarkers TIMP-2 and IGFBP7 for the assessment of acute kidney injury in dogs with pyometra"],"prefix":"10.3389","volume":"13","author":[{"given":"Larissa A. do N.","family":"Braz","sequence":"first","affiliation":[{"name":"Department of Clinical and Veterinary Surgery, School of Agricultural and Veterinary Sciences, S\u00e3o Paulo State University (Unesp)","place":["Jaboticabal, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suellen R.","family":"Maia","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (Unesp)","place":["Botucatu, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Gasser","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Agr\u00e1rias, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM)","place":["Una\u00ed, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan da R. N.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Mestrado e Doutorado Profissional em Produ\u00e7\u00e3o e Sanidade Animal (PGPSA) \u2013 Instituto Federal Catarinense","place":["Santa Rosa do Sul, SC, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alef Winter Oliveira","family":"Alvarenga","sequence":"additional","affiliation":[{"name":"Graduate Program in Animal Science, Veterinary Teaching Hospital, University of Franca (Unifran)","place":["Franca, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara Vilela","family":"Soares","sequence":"additional","affiliation":[{"name":"Graduate Program in Veterinary Science (PPGCV), College of Veterinary Medicine and Animal Science (FMVZ), Universidade Federal de Uberl\u00e2ndia (UFU)","place":["Uberl\u00e2ndia, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo A. R.","family":"Uscategui","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Medicina Veterinaria y Zootecnia, Universidad del Tolima","place":["Ibagu\u00e9, Colombia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrigo B.","family":"de Nardi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Veterinary Surgery, School of Agricultural and Veterinary Sciences, S\u00e3o Paulo State University (Unesp)","place":["Jaboticabal, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandro Z.","family":"Crivellenti","sequence":"additional","affiliation":[{"name":"Graduate Program in Veterinary Science (PPGCV), College of Veterinary Medicine and Animal Science (FMVZ), Universidade Federal de Uberl\u00e2ndia (UFU)","place":["Uberl\u00e2ndia, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref1","first-page":"171","article-title":"Perioperative urinary TIMP-2*IGFBP7 and acute kidney injury: a systematic review","volume":"90","author":"Ciuca","year":"2022","journal-title":"AANA J"},{"key":"ref2","year":"2016"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.2215\/CJN.00850122","article-title":"The pathophysiology of sepsis-associated AKI","volume":"17","author":"Kuwabara","year":"2022","journal-title":"Clin J Am Soc Nephrol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1016\/j.kint.2019.01.020","article-title":"Tissue inhibitor metalloproteinase-2 (TIMP-2) \u2022 IGF-binding protein-7 (IGFBP7) levels are associated with adverse outcomes in patients in the intensive care unit with acute kidney injury","volume":"95","author":"Xie","year":"2019","journal-title":"Kidney 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