{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:38:43Z","timestamp":1790829523859,"version":"4.1.0"},"reference-count":13,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"National Research Agency (ANR)","doi-asserted-by":"publisher","award":["ANR-16-RHUS-0003"],"award-info":[{"award-number":["ANR-16-RHUS-0003"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"GCS G4 (FHU CARNAVAL)","award":["ANR-16-RHUS-0003"],"award-info":[{"award-number":["ANR-16-RHUS-0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction. This study addressed the hypothesis that subtotal nephrectomy associated with a high-phosphorus diet (5\/6Nx + P) in rats represents a suitable animal model to mimic the cardiovascular consequences of chronic kidney disease (CKD) including calcified aortic valve disease (CAVD). Indeed, the latter contributes to the high morbidity and mortality of CKD patients and sorely lacks preclinical models for pathophysiological and pharmacological studies. Methods. Renal and cardiovascular function and structure were compared between sham-operated and 5\/6 Nx rats + P 10 to 12 weeks after surgery. Results. As expected, 11 weeks after surgery, 5\/6Nx + P rats developed CKD as demonstrated by their increase in plasma creatinine and urea nitrogen and decrease in glomerular filtration rate, estimated by using fluorescein-isothiocyanate-labelled sinistrin, anemia, polyuria, and polydipsia compared to sham-operated animals on a normal-phosphorus diet. At the vascular level, 5\/6Nx + P rats had an increase in the calcium content of the aorta; a decrease in mesenteric artery dilatation in response to a stepwise increase in flow, illustrating the vascular dysfunction; and an increase in blood pressure. Moreover, immunohistology showed a marked deposition of hydroxyapatite crystals in the aortic valve of 5\/6Nx + P rats. Echocardiography demonstrated that this was associated with a decrease in aortic valve cusp separation and an increase in aortic valve mean pressure gradient and in peak aortic valve velocity. Left-ventricular diastolic and systolic dysfunction as well as fibrosis were also present in 5\/6Nx + P rats. Conclusion. This study demonstrates that 5\/6Nx + P recapitulates the cardiovascular consequences observed in humans with CKD. In particular, the initiation of CAVD was shown, highlighting the interest of this animal model to study the mechanisms involved in the development of aortic stenosis and test new therapeutic strategies at an early stage of the disease.<\/jats:p>","DOI":"10.3390\/jcm12041539","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T01:36:52Z","timestamp":1676511412000},"page":"1539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure"],"prefix":"10.3390","volume":"12","author":[{"given":"Hind","family":"Messaoudi","sequence":"first","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Levesque","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"},{"name":"Department of Cardiology, CHU Rouen, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0854-1931","authenticated-orcid":false,"given":"Nicolas","family":"Perzo","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Berg","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"},{"name":"Department of Thoracic Surgery, CHU Rouen, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Feugray","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"},{"name":"Department of General Biochemistry, CHU Rouen, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Dumesnil","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3069-6208","authenticated-orcid":false,"given":"Val\u00e9ry","family":"Brunel","sequence":"additional","affiliation":[{"name":"Department of General Biochemistry, CHU Rouen, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5953-5785","authenticated-orcid":false,"given":"Dominique","family":"Guerrot","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"},{"name":"Department of Nephrology, CHU Rouen, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Eltchaninoff","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"},{"name":"Department of Cardiology, CHU Rouen, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Richard","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"},{"name":"Department of Pharmacology, CHU Rouen, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00efd","family":"Kamel","sequence":"additional","affiliation":[{"name":"UR UPJV 7517, M\u00e9canismes Physiopathologiques et Cons\u00e9quences des Calcifications Cardiovasculaires (MP3CV), Centre de Recherche Universitaire en Sant\u00e9, Universit\u00e9 de Picardie Jules Verne, F-80054 Amiens, France"},{"name":"Department of Biochemistry, Amiens-Picardie University Hospital, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Durand","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"},{"name":"Department of Cardiology, CHU Rouen, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0186-4797","authenticated-orcid":false,"given":"Youssef","family":"Bennis","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"},{"name":"UR UPJV 7517, M\u00e9canismes Physiopathologiques et Cons\u00e9quences des Calcifications Cardiovasculaires (MP3CV), Centre de Recherche Universitaire en Sant\u00e9, Universit\u00e9 de Picardie Jules Verne, F-80054 Amiens, France"},{"name":"Department of Pharmacology, Amiens-Picardie University Hospital, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0383-2342","authenticated-orcid":false,"given":"J\u00e9r\u00e9my","family":"Bellien","sequence":"additional","affiliation":[{"name":"INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France"},{"name":"Department of Pharmacology, CHU Rouen, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1161\/CIRCULATIONAHA.120.050686","article-title":"Cardiovascular Disease in Chronic Kidney Disease: Pathophysiological Insights and Therapeutic Options","volume":"143","author":"Jankowski","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lim, Y.J., Sidor, N.A., Tonial, N.C., Che, A., and Urquhart, B.L. (2021). Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets. Toxins, 13.","DOI":"10.3390\/toxins13020142"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.kint.2019.06.025","article-title":"Chronic kidney disease and valvular heart disease: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference","volume":"96","author":"Marwick","year":"2019","journal-title":"Kidney Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1088","DOI":"10.1161\/CIR.0000000000000979","article-title":"American Heart Association Council on the Kidney in Cardiovascular Disease and Stroke Council. Evaluation and Management of Aortic Stenosis in Chronic Kidney Disease: A Scientific Statement from the American Heart Association","volume":"143","author":"Shroff","year":"2021","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1161\/CIRCRESAHA.110.234138","article-title":"Calcific aortic valve stenosis: Methods, models, and mechanisms","volume":"108","author":"Miller","year":"2011","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.joim.2019.01.010","article-title":"Impact of high-fat diet and vitamin D3 supplementation on aortic stenosis establishment in waved-2 epidermal growth factor receptor mutant mice","volume":"17","author":"Colleville","year":"2019","journal-title":"J. Integr. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1159\/000506013","article-title":"A Rat Model with Multivalve Calcification Induced by Subtotal Nephrectomy and High-Phosphorus Diet","volume":"6","author":"Wang","year":"2020","journal-title":"Kidney Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"122234","DOI":"10.1016\/j.jchromb.2020.122234","article-title":"Two rapid, accurate liquid chromatography tandem mass spectrometry methods for the quantification of seven uremic toxins: An application for describing their accumulation kinetic profile in a context of acute kidney injury","volume":"1152","author":"Bennis","year":"2020","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1093\/ndt\/gfp225","article-title":"Transcutaneous measurement of glomerular filtration rate using FITC-sinistrin in rats","volume":"24","author":"Sadick","year":"2009","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.yjmcc.2011.11.015","article-title":"Soluble epoxide hydrolase inhibition improves myocardial perfusion and function in experimental heart failure","volume":"52","author":"Merabet","year":"2012","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Varennes, O., Mentaverri, R., Duflot, T., Kauffenstein, G., Objois, T., Lenglet, G., Avondo, C., Morisseau, C., Brazier, M., and Kamel, S. (2020). The Metabolism of Epoxyeicosatrienoic Acids by Soluble Epoxide Hydrolase Is Protective against the Development of Vascular Calcification. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124313"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.kint.2021.01.026","article-title":"Decreased monocyte calcium sensing receptor expression in patients with chronic kidney disease is associated with impaired monocyte ability to reduce vascular calcification","volume":"99","author":"Mary","year":"2021","journal-title":"Kidney Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1159\/000435838","article-title":"Left Ventricular Hypertrophy in Chronic Kidney Disease Patients: From Pathophysiology to Treatment","volume":"5","author":"Gorini","year":"2015","journal-title":"Cardiorenal. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1539\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:36:43Z","timestamp":1760121403000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,15]]},"references-count":13,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jcm12041539"],"URL":"https:\/\/doi.org\/10.3390\/jcm12041539","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,15]]}}}