{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:28:25Z","timestamp":1753878505027,"version":"3.41.2"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"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\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Transplantation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Novel approaches to improve long\u2010term outcomes in kidney transplant recipients are required.\u00a0Here<jats:bold>,\u00a0<\/jats:bold>we present the 5\u2010year data from a multicenter, prospective, Phase 3b trial evaluating treatment outcomes with standard (STD) or low (LOW) dose prolonged\u2010release tacrolimus (TAC) combined with ACEi\/ARB or other antihypertensive therapy (OAHT) in Canadian kidney transplant recipients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult\u00a0<jats:italic>de novo<\/jats:italic>\u00a0kidney transplant recipients were randomized 2 \u00d7 2 to STD or LOW dose TAC and ACEi\/ARB or OAHT. Patients had received a first or second transplant from a living or deceased donor and had \u2265 1 human leukocyte antigen mismatch with their donor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were 281 patients from 13 sites across Canada. Overall patient survival was 95.7% and was comparable between groups. Graft survival at study end was 89.7% in the LOW+OAHT group and 94.4%\u201397.1% in the other groups and BPAR, and Class II\u00a0<jats:italic>de novo\u00a0<\/jats:italic>donor\u2010specific antibodies (<jats:italic>dn<\/jats:italic>DSA) were higher in the LOW+OAHT group than in the other groups. However, these differences were not statistically significant.\u00a0Graft function, blood pressure (BP), and proteinuria were similar between the groups; however,\u00a0between 2\u00a0and 5 years\u00a0there was a 2\u2010fold or greater increase in the use of ACEi\/ARB in patients randomized initially to OAHT, mostly because of hypertension and proteinuria. There were no unexpected safety findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients randomized to LOW TAC with renin\u2010angiotensin system (RAS) blockade had similar outcomes at 5 years as patients treated with STD TAC with or without RAS blockade, whereas those randomized to LOW TAC without RAS blockade showed a non\u2010significant trend towards more rejections and <jats:italic>dn<\/jats:italic>DSA<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration:<\/jats:title><jats:p>ClinicalTrials.gov\u00a0identifier: NCT00933231<\/jats:p><\/jats:sec>","DOI":"10.1111\/ctr.70067","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T11:30:52Z","timestamp":1735558252000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Five\u2010Year Prospective, Randomized, Open\u2010Label Study of Standard\u2010Dose Versus Low\u2010Dose Prolonged\u2010Release Tacrolimus With or Without Angiotensin\u2010Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Post Kidney Transplantation"],"prefix":"10.1111","volume":"39","author":[{"given":"Patricia M.","family":"Campbell","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Alberta Hospitals  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4766-3333","authenticated-orcid":false,"given":"Marcelo","family":"Cantarovich","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine McGill University Health Centre  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azim","family":"Gangji","sequence":"additional","affiliation":[{"name":"Department of Medicine St Joseph's Healthcare Hamilton  Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Houde","sequence":"additional","affiliation":[{"name":"Department of Medicine L'H\u00f4tel\u2010Dieu de Qu\u00e9bec  Qu\u00e9bec City Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony M.","family":"Jevnikar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine London Health Sciences Centre  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix\u2010Mauricio","family":"Monroy\u2010Cuadros","sequence":"additional","affiliation":[{"name":"Division of Transplant Surgery Foothills Medical Centre  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter W.","family":"Nickerson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Immunology Health Sciences Centre  Winnipeg Manitoba Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel R.","family":"P\u00e2quet","sequence":"additional","affiliation":[{"name":"Division of Nephrology H\u00f4pital Notre\u2010Dame du CHUM  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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