{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T14:19:32Z","timestamp":1768141172397,"version":"3.49.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>The aim of this study was to investigate whether the combination of low-dose sirolimus (SRL) and low-dose extended-release tacrolimus (TAC) compared to normal-dose extended-release TAC results in a difference in the renal function and comparable rates of rejection, graft and patient survival at 36 months after transplantation. This study was an open-label, multicenter randomized, controlled trial. Patients were randomized to once daily normal-dose extended-release TAC (control group) or once daily combination therapy of SRL and low-dose extended-release TAC (interventional group). The primary endpoint was the cumulative incidence of chronic kidney disease (CKD) defined as grade \u22653 (eGFR &lt;60\u00a0mL\/min\/1.73\u00a0m<jats:sup>2<\/jats:sup>) at 36 months after transplantation. In total, 196 patients were included. CKD at 36 months was not different between the control and interventional group (50.8%, 95% confidence interval (CI) 39.7% \u2013 59.9%) <jats:italic toggle=\"yes\">vs.<\/jats:italic> 43.7%, 95% CI: 32.8% - 52.8%). Only at six months after transplantation, the eGFR was higher in the interventional group compared to the control group (mean eGFR 73.1\u00b115 <jats:italic toggle=\"yes\">vs.<\/jats:italic> 67.6\u00b116\u00a0mL\/min\/1.73\u00a0m<jats:sup>2<\/jats:sup>, <jats:italic toggle=\"yes\">P<\/jats:italic>=0.02) in the intention to treat population. No differences in the secondary endpoints and the number of serious adverse events were found between the groups. Once-daily low-dose SRL combined with low-dose extended-release TAC does ultimately not provide less CKD grade \u22653 at 36 months compared to normal-dose extended-release TAC.<\/jats:p>","DOI":"10.1097\/lvt.0000000000000003","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T20:07:25Z","timestamp":1674245245000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Three-year results of renal function in liver transplant recipients on low-dose sirolimus and tacrolimus: a multicenter randomized, controlled trial"],"prefix":"10.1097","author":[{"given":"M.B.","family":"Mulder","sequence":"first","affiliation":[{"name":"Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"},{"name":"the Erasmus MC Transplant Institute, Rotterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"van Hoek","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, LUMC, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.P.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.G.","family":"Polak","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"},{"name":"the Erasmus MC Transplant Institute, Rotterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.P.J.","family":"Alwayn","sequence":"additional","affiliation":[{"name":"Department of Surgery, LUMC, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.P.","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.C.M.","family":"de Winter","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"},{"name":"the Erasmus MC Transplant Institute, Rotterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Verhey-Hart","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"},{"name":"the Erasmus MC Transplant Institute, Rotterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.S.","family":"Erler","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"},{"name":"Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.M.","family":"den Hoed","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"},{"name":"the Erasmus MC Transplant Institute, Rotterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.J.","family":"Metselaar","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands"},{"name":"the Erasmus MC Transplant Institute, Rotterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"R1-20230216","first-page":"CD005161","article-title":"Cyclosporin versus tacrolimus for liver transplanted patients","volume":"4","author":"Haddad","year":"2006","journal-title":"Cochrane Database Syst Rev"},{"key":"R2-20230216","doi-asserted-by":"crossref","first-page":"e0160421","DOI":"10.1371\/journal.pone.0160421","article-title":"Systematic review and meta-analysis of tacrolimus versus ciclosporin as primary immunosuppression after liver transplant","volume":"11","author":"Muduma","year":"2016","journal-title":"PLoS One"},{"key":"R3-20230216","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/00000658-199009000-00008","article-title":"Liver, kidney, and thoracic organ transplantation under FK 506","volume":"212","author":"Todo","year":"1990","journal-title":"Ann 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