{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T14:53:14Z","timestamp":1786719194210,"version":"build-2736575974"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ZonMw","award":["848042001"],"award-info":[{"award-number":["848042001"]}]},{"DOI":"10.13039\/100007560","name":"Chiesi Farmaceutici","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007560","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,4]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n Low-dose tacrolimus, everolimus, and prednisolone did not result in a higher rate of successful transplantation in older kidney transplant recipients.<\/jats:p>\n <\/jats:list-item>\n \n Low-dose tacrolimus, everolimus, and prednisolone did not result in better kidney function or fewer infections in older kidney transplant recipients.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n We hypothesized that older kidney transplant recipients receiving low-dose tacrolimus, everolimus, and prednisolone (TEP) have better outcomes than patients receiving standard-dose tacrolimus, mycophenolate mofetil, and prednisolone (TMP).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The OPTIMIZE study was a randomized clinical trial in kidney transplant recipients age \u226565 years. Patients receiving a kidney from a deceased donor older than 65 years (stratum A) or a kidney from a deceased donor younger than 65 years or a living donor (stratum B) were included. Patients were randomized to TEP or TMP groups. Tacrolimus target trough levels in the TEP group were 5\u20137 ng\/ml until 3 months, 2\u20134 ng\/ml from 3 to 6 months, and 1.5\u20134 ng\/ml from 6 months onwards. Tacrolimus target trough levels in the TMP group were 8\u201312, 6\u201310, and 5\u20138 ng\/ml. Everolimus target trough levels were 3\u20136\n \u00b5<\/jats:italic>\n g\/L. The primary end point of successful transplantation was defined as being alive with a functioning graft with an eGFR above a predefined threshold at 2 years after transplantation. Predefined eGFR thresholds were 30 (stratum A) or 45 ml\/min per 1.73 m\n 2<\/jats:sup>\n (stratum B).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 379 patients were randomized, of whom 198 were in stratum A (TEP 97, TMP 101) and 181 in stratum B (TEP 90, TMP 91). The median trough levels for everolimus and tacrolimus were within the target range throughout the study. There was no statistically significant difference in successful transplantation at 2 years between the groups (TEP 94 [50%], TMP 110 [57%]; difference 7% [95% confidence interval, \u221217 to 3]\n P<\/jats:italic>\n = 0.91). Regarding the predefined secondary outcomes, patient survival (TEP 167 [89%], TMP 171 [89%];\n P<\/jats:italic>\n = 0.95) and graft survival (TEP 155 [83%], TMP 162 [84%];\n P<\/jats:italic>\n = 0.65) did not differ significantly. Within strata A and B, there were no significant differences in the end points.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Immunosuppression with low-dose tacrolimus, everolimus, and prednisolone did not result in a higher rate of successful transplantation in\n de novo<\/jats:italic>\n older kidney transplant recipients compared with immunosuppression with standard-dose TMP.\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n ClinicalTrials.gov, NCT03797196.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000000924","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T17:00:08Z","timestamp":1762534808000},"page":"814-824","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Immunosuppression in Older Kidney Transplant Recipients"],"prefix":"10.1681","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0904-3969","authenticated-orcid":false,"given":"Jan-Stephan F.","family":"Sanders","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7812-8221","authenticated-orcid":false,"given":"Silke E.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9548-4985","authenticated-orcid":false,"given":"Jip","family":"Jonker","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-6270","authenticated-orcid":false,"given":"Frederike J.","family":"Bemelman","sequence":"additional","affiliation":[{"name":"Renal Transplant Unit, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9435-6208","authenticated-orcid":false,"given":"Michiel G.H.","family":"Betjes","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC Transplant Institute, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9284-3595","authenticated-orcid":false,"given":"Aiko P.J.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Leiden Transplant Center, Leiden University Medical Center, Leiden University, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4935-9765","authenticated-orcid":false,"given":"Luuk","family":"Hilbrands","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3712-7171","authenticated-orcid":false,"given":"Marc","family":"Hilhorst","sequence":"additional","affiliation":[{"name":"Renal Transplant Unit, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5546-9680","authenticated-orcid":false,"given":"Dirk R.J.","family":"Kuypers","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Vart","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2561-5533","authenticated-orcid":false,"given":"Arjan D.","family":"van Zuilen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1871-1962","authenticated-orcid":false,"given":"Dennis 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