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It is silent in the early stages and gradually progresses, inducing renal physiological and structural alterations. Moreover, CKD is associated with impaired life quality, increased risk for cardiovascular diseases, and reduced life expectancy. Different CKD animal models differ in underlying etiology, time of onset, and associated diseases. The 0.25% adenine diet induces progressive kidney damage, constituting an adequate model mimicking human CKD. Vasopressin (VP) was postulated as a mediator of CKD, mainly acting through its V2 receptors. However, the molecular mechanisms involved in the pathogenesis of this condition and its progression still are not entirely understood. This study aimed to evaluate if AQP2 expression is altered in an adenine-induced model of CKD in rats at early stages of development (two weeks) and to assess a potential beneficial effect of Tolvaptan (a V2 receptor antagonist) treatment. We showed an increased renal medullary AQP2 expression at two weeks of adenine administration. This increase was mainly cytoplasmic, explaining the increased urinary volume of CKD rats and suggesting a possible non-canonical role for AQP2. In addition, Tolvaptan effectively inhibited the V2 receptor in both control and CKD rats, decreasing AQP2 expression and increasing diuresis. Moreover, Tolvaptan slightly reduced BUN and plasma creatinine. On the other hand, the renal alterations induced by adenine in CKD rats were not prevented by Tolvaptan.<\/jats:p>","DOI":"10.1371\/journal.pone.0314827","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T18:25:21Z","timestamp":1738261521000},"page":"e0314827","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Aquaporin-2 in the early stages of the adenine-induced chronic kidney disease model"],"prefix":"10.1371","volume":"20","author":[{"given":"Lucas H.","family":"Oronel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ortiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Yarza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sof\u00eda","family":"Gayone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Davio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Majowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8090-2458","authenticated-orcid":true,"given":"Maria Florencia","family":"Albertoni Borghese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"issue":"10302","key":"pone.0314827.ref001","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/S0140-6736(21)00519-5","article-title":"Chronic kidney disease","volume":"398","author":"K Kalantar-Zadeh","year":"2021","journal-title":"Lancet (London, England)"},{"issue":"10105","key":"pone.0314827.ref002","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/S0140-6736(17)30788-2","article-title":"Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy","volume":"390","author":"A Levin","year":"2017","journal-title":"Lancet (London, England)"},{"key":"pone.0314827.ref003","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-981-13-8871-2_1","article-title":"Prevalence and Disease Burden of Chronic Kidney Disease","volume":"1165","author":"JC Lv","year":"2019","journal-title":"Adv Exp Med Biol"},{"issue":"7","key":"pone.0314827.ref004","doi-asserted-by":"crossref","first-page":"e0158765","DOI":"10.1371\/journal.pone.0158765","article-title":"Global Prevalence of Chronic Kidney Disease\u2014A Systematic Review and Meta-Analysis","volume":"11","author":"NR Hill","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"pone.0314827.ref005","doi-asserted-by":"crossref","first-page":"e13641","DOI":"10.1111\/apha.13641","article-title":"Local cyclic adenosine monophosphate signalling cascades-Roles and targets in chronic kidney disease","volume":"232","author":"A Sholokh","year":"2021","journal-title":"Acta Physiol (Oxf)"},{"key":"pone.0314827.ref006","first-page":"415","volume-title":"Nature reviews. 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