{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:54:09Z","timestamp":1788497649424,"version":"build-2803163510"},"reference-count":63,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T00:00:00Z","timestamp":1686614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL-137004"],"award-info":[{"award-number":["HL-137004"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"David and Helen Boone Foundation Research Fund","award":["HL-137004"],"award-info":[{"award-number":["HL-137004"]}]},{"name":"University of Toledo Women and Philanthropy Genetic Analysis Instrumentation Center","award":["HL-137004"],"award-info":[{"award-number":["HL-137004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diet-induced models of chronic kidney disease (CKD) offer several advantages, including clinical relevance and animal welfare, compared with surgical models. Oxalate is a plant-based, terminal toxic metabolite that is eliminated by the kidneys through glomerular filtration and tubular secretion. An increased load of dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction, and eventually CKD. Dahl-Salt-Sensitive (SS) rats are a common strain used to study hypertensive renal disease; however, the characterization of other diet-induced models on this background would allow for comparative studies of CKD within the same strain. In the present study, we hypothesized that SS rats on a low-salt, oxalate rich diet would have increased renal injury and serve as novel, clinically relevant and reproducible CKD rat models. Ten-week-old male SS rats were fed either 0.2% salt normal chow (SS-NC) or a 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks.Real-time PCR demonstrated an increased expression of inflammatory marker interleukin-6 (IL-6) (p &lt; 0.0001) and fibrotic marker Timp-1 metalloproteinase (p &lt; 0.0001) in the renal cortex of SS-OX rat kidneys compared with SS-NC. The immunohistochemistry of kidney tissue demonstrated an increase in CD-68 levels, a marker of macrophage infiltration in SS-OX rats (p &lt; 0.001). In addition, SS-OX rats displayed increased 24 h urinary protein excretion (UPE) (p &lt; 0.01) as well as significant elevations in plasma Cystatin C (p &lt; 0.01). Furthermore, the oxalate diet induced hypertension (p &lt; 0.05). A renin\u2013angiotensin\u2013aldosterone system (RAAS) profiling (via liquid chromatography\u2013mass spectrometry; LC\u2013MS) in the SS-OX plasma showed significant (p &lt; 0.05) increases in multiple RAAS metabolites including angiotensin (1\u20135), angiotensin (1\u20137), and aldosterone. The oxalate diet induces significant renal inflammation, fibrosis, and renal dysfunction as well as RAAS activation and hypertension in SS rats compared with a normal chow diet. This study introduces a novel diet-induced model to study hypertension and CKD that is more clinically translatable and reproducible than the currently available models.<\/jats:p>","DOI":"10.3390\/ijms241210062","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T01:32:15Z","timestamp":1686706335000},"page":"10062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel Model of Oxalate Diet-Induced Chronic Kidney Disease in Dahl-Salt-Sensitive Rats"],"prefix":"10.3390","volume":"24","author":[{"given":"Prabhatchandra","family":"Dube","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishnavi","family":"Aradhyula","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo College of 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W.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8315-8338","authenticated-orcid":false,"given":"Jacob A.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia M.","family":"Soehnlen","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambika","family":"Sood","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43606, 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1110 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance D.","family":"Dworkin","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6919-6342","authenticated-orcid":false,"given":"Steven T.","family":"Haller","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5265-0142","authenticated-orcid":false,"given":"David 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