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While CnIs have significantly increased graft survival and transformed the patient standard of care, their use has been overshadowed by a number of undesired side effects. For instance, CnI\u2010associated nephrotoxicity has been reported since early studies and remains a major therapeutic concern. The occurrence of several ion imbalances alongside hypertension was also noted early on, indicating the involvement of the renin\u2013angiotensin\u2013aldosterone system (RAAS) in CnI\u2010mediated toxicity. However, the literature in this field is crowded with conflicting reports from clinical trials as well as studies using animal and invitro models. With this review, we aim to provide a structured and updated overview of the physiological and pathophysiological evidence supporting the involvement of the classical RAAS in CnI\u2010associated toxicity.<\/jats:p>","DOI":"10.1111\/apha.14248","type":"journal-article","created":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T06:51:12Z","timestamp":1729925472000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Calcineurin inhibitors and the renin\u2013angiotensin\u2013aldosterone system"],"prefix":"10.1111","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-2158","authenticated-orcid":false,"given":"Mesut","family":"Berber","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Harvard Medical School and Division of Endocrinology Boston Children's Hospital  Boston Massachusetts 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