{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:06:20Z","timestamp":1789146380570,"version":"build-2803163510"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"abstract":"\n Background:<\/jats:title>\n Tacrolimus is the cornerstone of immunosuppressive treatment after kidney transplantation. Its application requires therapeutic drug monitoring, which is routinely performed by assessment of whole blood tacrolimus concentrations (WBTC) that largely comprises a pharmacologically inactive fraction. Monitoring tacrolimus exposure using the plasma tacrolimus concentration (PTC) may better reflect the pharmacological active fraction. We hypothesized that PTC better reflects effectivity and toxicity than WBTC.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n The ALLEGRO trial randomized 295 kidney transplant recipients (KTR) to standard triple immunosuppression, lower tacrolimus exposure or withdrawal of prednisolone. PTC was measured using LC-MS\/MS. Associations between tacrolimus concentrations and eGFR were analyzed using linear regression, with bootstrap resampling used to compare PTC and WBTC. Associations with biopsy results and rejection were evaluated using logistic regression, and infection risk was assessed with joint modeling.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Mean age was 56.5 \u00b1 13.2 years, 95 (32%) were female. The mean PTC during the first month post-transplantation (0.31 \u00b1 0.17 ng\/mL) was negatively associated with eGFR at four weeks (st.\u03b2=-0.17 (-0.29;-0.05), P=0.006), whereas mean WBTC was not (st.\u03b2=0.09 (-0.03;0.22), P=0.15), the difference between these associations was statistically significant (P=0.004). Late mean PTC (6.5\u201324 months; 0.15 \u00b1 0.07 ng\/mL) was negatively associated with eGFR at two years (st.\u03b2=-0.19 (-0.35;-0.03), P=0.02), mean WBTC was not (st.\u03b2=0.04 (-0.13;0.20), P=0.66), this difference was also statistically significant (P=0.02). At two years, 10 (14%) out of the 71 protocol biopsies showed moderate-to-severe arteriolar hyalinosis. Although in a limited number of events, late mean PTC was significantly associated with risk of arteriolar hyalinosis (OR=1.96 (1.07;3.80), P=0.03), WBTC was not (OR=1.65 (0.83;3.53), P=0.17). Neither PTC nor WBTC was significantly associated with risk of infection in univariable analysis. Twenty-two KTR (7%) experienced biopsy-proven rejection, neither PTC nor WBTC was associated with rejection.<\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Larger studies are needed to determine whether late PTC is a better marker than WBTC to detect potential tacrolimus-related nephrotoxicity in KTR.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.0000001214","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:10:06Z","timestamp":1789143006000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Plasma versus Whole Blood Tacrolimus Concentration and Outcomes After Kidney Transplantation"],"prefix":"10.2215","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9548-4985","authenticated-orcid":false,"given":"Jip","family":"Jonker","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2637-4046","authenticated-orcid":false,"given":"Joost C.","family":"van den Born","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Meander Medical Center, Amersfoort, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0011-115X","authenticated-orcid":false,"given":"Daan","family":"Kremer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7818-6656","authenticated-orcid":false,"given":"Marit S.","family":"van Sandwijk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Amsterdam UMC, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3490-1993","authenticated-orcid":false,"given":"Armin","family":"Gelinck","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology; and Leiden Transplant Center, Leiden University Medical Center, University of Leiden, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7694-8381","authenticated-orcid":false,"given":"Soufian","family":"Meziyerh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology; and Leiden Transplant Center, Leiden University Medical Center, University of Leiden, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3219-253X","authenticated-orcid":false,"given":"Dirk Jan A.R.","family":"Moes","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, University of Leiden, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1357-9248","authenticated-orcid":false,"given":"Cornelis","family":"Smit","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"},{"name":"Pharmacometrics Expertise Center Of the Northern Netherlands, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4398-4877","authenticated-orcid":false,"given":"Antonio W.","family":"Gomes-Neto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, 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":"Department of Internal Medicine, Division of Nephrology, Amsterdam UMC, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Vart","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2228-4676","authenticated-orcid":false,"given":"Stefan P.","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-6791","authenticated-orcid":false,"given":"Stephan J.L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9676-1722","authenticated-orcid":false,"given":"Sandrine","family":"Florquin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, 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":"Department of Internal Medicine, Division of Nephrology; and Leiden Transplant Center, Leiden University Medical Center, University of Leiden, Leiden, 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":"Department of Internal Medicine, Division of Nephrology, Amsterdam UMC, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1429-4789","authenticated-orcid":false,"given":"Daan J.","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"},{"name":"Department of Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0904-3969","authenticated-orcid":false,"given":"Jan Stephan F.","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,9,11]]},"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.2215\/CJN.0000001214","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:10:06Z","timestamp":1789143006000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.2215\/CJN.0000001214"}},"subtitle":["Post Hoc Analysis of the ALLEGRO Trial"],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":0,"URL":"https:\/\/doi.org\/10.2215\/cjn.0000001214","relation":{},"ISSN":["1555-9041","1555-905X"],"issn-type":[{"value":"1555-9041","type":"print"},{"value":"1555-905X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"assertion":[{"value":"2026-02-17","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}