{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:14:39Z","timestamp":1790100879379,"version":"4.0.1"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":398,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["SBP 2020 006001"],"award-info":[{"award-number":["SBP 2020 006001"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007229","name":"Bijzonder Onderzoeksfonds UGent","doi-asserted-by":"publisher","award":["DOC 2020 004701"],"award-info":[{"award-number":["DOC 2020 004701"]}],"id":[{"id":"10.13039\/501100007229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018065","name":"EveryCat Health Foundation","doi-asserted-by":"publisher","award":["CaPK22-002"],"award-info":[{"award-number":["CaPK22-002"]}],"id":[{"id":"10.13039\/100018065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["SBP 2020 006001"],"award-info":[{"award-number":["SBP 2020 006001"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007229","name":"Bijzonder Onderzoeksfonds UGent","doi-asserted-by":"publisher","award":["DOC 2020 004701"],"award-info":[{"award-number":["DOC 2020 004701"]}],"id":[{"id":"10.13039\/501100007229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018065","name":"EveryCat Health Foundation","doi-asserted-by":"publisher","award":["CaPK22\u2010002"],"award-info":[{"award-number":["CaPK22\u2010002"]}],"id":[{"id":"10.13039\/100018065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although gut-derived uremic toxins are increased in azotemic chronic kidney disease (CKD) in cats and implicated in disease progression, it remains unclear if augmented formation or retention of these toxins is associated with the development of renal azotemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Assess the association between gut-derived toxins (ie, indoxyl-sulfate, p-cresyl-sulfate, and trimethylamine-N-oxide [TMAO]) and the onset of azotemic CKD in cats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Forty-eight client-owned cats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Nested case-control study, comparing serum and urine gut-derived uremic toxin abundance at 6-month intervals between initially healthy cats that developed azotemic CKD (n\u2009=\u200922) and a control group (n\u2009=\u200926) that remained healthy, using a targeted metabolomic approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cats in the CKD group had significantly higher serum indoxyl-sulfate (mean [SD], 1.44 [1.06] vs 0.83 [0.46]; P\u2009=\u2009.02) and TMAO (mean [SD], 1.82 [1.80] vs 1.60 [0.62]; P\u2009=\u2009.01) abundance 6\u2009months before the detection of azotemic CKD. Furthermore, logistic regression analysis indicated that indoxyl-sulfate (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.2-9.0; P\u2009=\u2009.04) and TMAO (OR: 3.9; 95% CI: 1.4-11; P\u2009=\u2009.03) were predictors for the onset of azotemia 6\u2009months before diagnosis. However, renal function biomarkers creatinine, symmetric dimethylarginine, and urinary specific gravity were significantly correlated with indoxyl-sulfate and TMAO abundance, causing a loss in predictive significance after correction for these factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Impaired gut-derived uremic toxin handling is apparent at least 6\u2009months before the diagnosis of azotemia, likely reflecting an already ongoing decrease in GFR, tubular function, or both. A direct causal relationship between gut-derived uremic toxicity and the initiation of CKD in cats is still lacking.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.17289","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T04:39:57Z","timestamp":1735533597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Alterations in gut-derived uremic toxins before the onset of azotemic chronic kidney disease in cats"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6612-5936","authenticated-orcid":false,"given":"Laurens","family":"Van Mulders","sequence":"first","affiliation":[{"name":"Ghent University Faculty of Veterinary Medicine, Department of Small Animals, , Merelbeke,","place":["Belgium"]},{"name":"Infectiology and Public Health, Laboratory of Integrative Metabolomics, Ghent University Faculty of Veterinary Medicine, Department 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Merelbeke,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-2561","authenticated-orcid":false,"given":"Femke","family":"Mortier","sequence":"additional","affiliation":[{"name":"Ghent University Faculty of Veterinary Medicine, Department of Small Animals, , Merelbeke,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Vanhaecke","sequence":"additional","affiliation":[{"name":"Infectiology and Public Health, Laboratory of Integrative Metabolomics, Ghent University Faculty of Veterinary Medicine, Department of Translational Physiology, , Merelbeke,","place":["Belgium"]},{"name":"Queen's University Belfast, School of Biological Sciences, Institute for Global Food Security , 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