{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:26:14Z","timestamp":1787725574037,"version":"build-2784847793"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"JSPS KAKENHI","award":["JP16K10445"],"award-info":[{"award-number":["JP16K10445"]}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"crossref","award":["24ek0510040h0002"],"award-info":[{"award-number":["24ek0510040h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Nephrol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non-invasive biomarkers are essential for monitoring transplant health, particularly for detecting acute rejection. Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker in solid organ transplantation, but optimized methodology and comprehensive evaluation in kidney transplantation (KTx), especially in Japan, are currently limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a customized approach for dd-cfDNA quantification and evaluated its utility as a biomarker in KTx. In this prospective longitudinal study, 322 blood samples were collected from 39 KTx recipients, mostly within the first year and up to 5 years post-transplant. Quantification was performed using a modified targeted sequencing protocol using a 1,000-SNP probe panel tailored to East Asian genetic backgrounds. The resulting dd-cfDNA values were correlated with clinical parameters and histological findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      General longitudinal dynamics of dd-cfDNA in KTx patients were comprehensively described. Elevated dd-cfDNA was consistently associated with acute rejection and graft injuries. In particular, dd-cfDNA significantly distinguished rejection from non-rejection episodes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.9\u2009\u00d7\u200910\n                      <jats:sup>\u2212\u20094<\/jats:sup>\n                      ) and showed moderate consistency with serum markers and biopsy findings. Noticeable surges of dd-cfDNA were reported in antibody-mediated rejection and various forms of kidney injury. Distinct from conventional serum markers, dd-cfDNA exhibited a significant inverse correlation with immunosuppressant trough levels (Spearman\u2019s rho = \u2212\u20090.25,\n                      <jats:italic>p\u2009=\u2009<\/jats:italic>\n                      8\u2009\u00d7\u200910\n                      <jats:sup>\u2212\u20093<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study demonstrated that dd-cfDNA is a robust, non-invasive biomarker for detecting allograft rejection and injury in KTx and is superior for monitoring patients\u2019 immunosuppressive response. We also present a scalable, cost-effective sequencing-based methodology for quantifying dd-cfDNA, suitable for clinical application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10157-026-02889-8","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:23:05Z","timestamp":1780392185000},"page":"1368-1379","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Applications of donor-derived cell-free DNA in kidney transplantation healthcare: view from a prospective single-center study"],"prefix":"10.1007","volume":"30","author":[{"given":"Phuong Thanh","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-1159","authenticated-orcid":false,"given":"Hirofumi","family":"Nakaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Mitsunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromichi","family":"Aoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kitamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Saigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ituro","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"2889_CR1","doi-asserted-by":"publisher","unstructured":"Tonelli M, Wiebe N, Knoll G, Bello A, Browne S, Jadhav D, et al. 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All the authors have declared no competing interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures performed in this study was approved by the institutional ethical boards of National Hospital Organization Chiba-East Hospital (Approved ID: 41) and the National Institute of Genetics (Approved ID: 28\u2009\u2212\u20097). This study was in accordance with the 1964 Helsinki declaration including its later amendments, and with the Declaration of Istanbul. This article does not contain any studies with animals performed by any of the authors.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}}]}}