{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:23:49Z","timestamp":1789629829265,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T00:00:00Z","timestamp":1540944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01\u2010AI058013"],"award-info":[{"award-number":["U01\u2010AI058013"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19\u2010AI070119"],"award-info":[{"award-number":["U19\u2010AI070119"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Transplantation"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Suboptimal immunosuppression after kidney transplantation contributes to toxicity and loss of efficacy. Little is known regarding the impact of intra\u2010patient variability of tacrolimus (TAC) doses and troughs in the early post\u2010transplant period or the influence of genetic variants on variability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Coefficients of variation (CV) of TAC troughs and doses of 1226 European American (EA) and 246 African American (AA) adult recipients enrolled in DeKAF Genomics were compared for association with acute rejection and graft failure. Additionally, the influence of recipients\u2019 number of CYP3A5 loss\u2010of\u2010function alleles was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Acute rejection was associated with greater CV of dose in AA (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and EA recipients (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.012). Graft failure was associated with a greater CV of dose (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.022) and trough (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) in AA, and higher CV of trough (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.024) in EA recipients. In EA, CYP3A5 loss\u2010of\u2010function alleles were associated with decreased CV of trough (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0042) and increased CV of dose (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CYP3A5 loss\u2010of\u2010function alleles influence intra\u2010patient TAC trough and dose variability. High variability of TAC dose increases risk of acute rejection. High variability of TAC trough increases risk of graft failure. Early clinical recognition of TAC dose and trough variability may improve patient management and outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ctr.13424","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T06:48:33Z","timestamp":1539586113000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Tacrolimus trough and dose intra\u2010patient variability and CYP3A5 genotype: Effects on acute rejection and graft failure in European American and African American kidney transplant recipients"],"prefix":"10.1111","volume":"32","author":[{"given":"Stephan R.","family":"Seibert","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Schladt","sequence":"additional","affiliation":[{"name":"Chronic Disease Research Group, Minneapolis Medical Research Foundation Hennepin County Medical Center Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baolin","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health University of Minnesota Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Guan","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health University of Minnesota Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Dorr","sequence":"additional","affiliation":[{"name":"Minneapolis Medical Research Foundation Hennepin County Medical Center Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory P.","family":"Remmel","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy University of Minnesota Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur J.","family":"Matas","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Minnesota Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roslyn B.","family":"Mannon","sequence":"additional","affiliation":[{"name":"Department of Nephrology University of Alabama Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7607-0430","authenticated-orcid":false,"given":"Ajay K.","family":"Israni","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Hennepin County Medical Center Epidemiology &amp; Community Health University of Minnesota Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Oetting","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cell Biology, and Development University of Minnesota Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4145-7045","authenticated-orcid":false,"given":"Pamala A.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12155"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2015.01.002"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13495"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.15.42"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.5414\/CP202152"},{"key":"e_1_2_9_7_1","unstructured":"JacobsonP MillerM SchladtD et al.Variants associated with tacrolimus troughs in European American kidney transplant recipients: A genome wide association study. 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