{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:29:23Z","timestamp":1790612963659,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":20,"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":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>This study investigated the impact of immunosuppressive drug concentrations on microvascular inflammation (MVI) in kidney transplant recipients with negative donor\u2010specific antibodies (DSA) against human leukocyte antigen (HLA) and negative C4d deposition in peritubular capillaries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed data from 268 living kidney transplant recipients at the Department of Urology, University of Osaka, Japan. Patients received immunosuppressive therapy comprising extended\u2010release tacrolimus, mycophenolate mofetil (MMF), and\/or everolimus, with or without steroids. Graft biopsies were routinely performed at 3, 12, 36 and 60\u00a0months post\u2010surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No significant differences were observed between the MVI+DSA\u2010C4d\u2010 and MVI\u2010DSAC4d groups regarding graft survival rates (95.5% vs. 96.6%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.772) or patient survival rates (95.7%\u00a0vs. 95.9%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.735). Lower tacrolimus and everolimus concentrations were significantly associated with an increased risk of MVI+DSA\u2010C4d\u2010 (tacrolimus: OR, 0.169; 95% CI, 0.055\u20130.515; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.002; everolimus: OR, 0.386; 95% CI, 0.171\u20130.874; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.022). In contrast, MPA concentration was not significantly associated with MVI+DSA\u2010C4d\u2010 (OR, 0.994; 95% CI, 0.554\u20131.780; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.984). Steroid discontinuation did not significantly impact the risk of MVI+DSA\u2010C4d\u2010 (OR, 1.980; 95% CI, 0.318\u201312.000; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.470).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Lower trough levels of tacrolimus and everolimus correlated with a higher incidence of antibody\u2010independent MVI, supporting the need for tailored immunosuppressive regimens in kidney transplantation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ctr.70112","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:20:34Z","timestamp":1740129634000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor\u2010Specific Antibodies, and C4d\u2010Negative Status in Kidney Transplant Recipients"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5339-4312","authenticated-orcid":false,"given":"Yoichi","family":"Kakuta","sequence":"first","affiliation":[{"name":"Department of Urology Osaka Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Maegawa\u2010Higa","sequence":"additional","affiliation":[{"name":"Department of Urology Osaka Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichi","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Urology Osaka Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Fukae","sequence":"additional","affiliation":[{"name":"Department of Urology Osaka Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-7820","authenticated-orcid":false,"given":"Ryo","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Urology Osaka Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Yonishi","sequence":"additional","affiliation":[{"name":"Department of Nephrology Osaka Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"Department of Urology Osaka Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Namba\u2010Hamano","sequence":"additional","affiliation":[{"name":"Department of Nephrology Osaka Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Isaka","sequence":"additional","affiliation":[{"name":"Department of Nephrology Osaka Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Nonomura","sequence":"additional","affiliation":[{"name":"Department of Urology Osaka Graduate School of Medicine  Suita Osaka 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Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ctr.70112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T09:50:46Z","timestamp":1747907446000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ctr.70112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/ctr.70112"],"URL":"https:\/\/doi.org\/10.1111\/ctr.70112","archive":["Portico"],"relation":{},"ISSN":["0902-0063","1399-0012"],"issn-type":[{"value":"0902-0063","type":"print"},{"value":"1399-0012","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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