{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:02:03Z","timestamp":1784721723902,"version":"3.55.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for allograft injury in kidney transplant recipients. This single-center study aimed to evaluate the clinical indications for dd-cfDNA testing, its association with biopsy findings, and the comparative utility of dd-cfDNA expressed as a percentage versus absolute copy number.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis was conducted of 571 dd-cfDNA measurements from 313 kidney transplant recipients at the Charit\u00e9 Berlin Transplant Center from May 2020 to May 2025. The clinical indications for testing, biopsy, and rejection predictors were assessed using multivariable logistic regression and linear regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Elevated creatinine (29%), elevated urine albumin-to-creatinine ratio (UACR, 10%), donor-specific antibody positivity (10%), history of rejection (9%), immunosuppression reduction (5%), and combined reasons (38%) were the most frequent indications for dd-cfDNA testing. Elevated UACR was the only independent predictor of biopsy (odds ratio [OR], 3.02; 95% confidence interval [CI], 1.39\u20136.58;\n                      <jats:italic>p<\/jats:italic>\n                      =\u202f0.005). In the biopsy cohort, the dd-cfDNA percentage (OR, 5.46; 95% CI, 2.89\u201313.70;\n                      <jats:italic>p<\/jats:italic>\n                      =\u202f0.0035) and copies\/mL (OR, 7.05; 95% CI, 1.01\u201321.09;\n                      <jats:italic>p<\/jats:italic>\n                      =\u202f0.0062) independently predicted rejection. ROC analysis indicated good discrimination of rejection for both copies\/mL (AUC, 0.781) and percentage (AUC, 0.820). DCA revealed that both dd-cfDNA formats offered greater net clinical benefits for rejection prediction than the conventional markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although biopsy decisions primarily rely on conventional clinical parameters, dd-cfDNA can independently identify rejection and improve decision-making when integrated into multimodal post-transplant monitoring strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1890561","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:12:03Z","timestamp":1784718723000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-world utilization patterns and association of dd-cfDNA with biopsy and rejection"],"prefix":"10.3389","volume":"13","author":[{"given":"Ivana","family":"Dedinsk\u00e1","sequence":"first","affiliation":[{"name":"Transplant-Nephrology Department, University Hospital Martin","place":["Martin, Slovakia"]},{"name":"Internal Department I, Jessenius Faculty of Medicine, Comenius University and University Hospital Martin","place":["Martin, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Akifova","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Intensive Care, Charit\u00e9 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilgin","family":"Osmanodja","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Intensive Care, Charit\u00e9 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Halleck","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Intensive Care, Charit\u00e9 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva V.","family":"Schrezenmeier","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Intensive Care, Charit\u00e9 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parthenopi","family":"Avaniadi","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Intensive Care, Charit\u00e9 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"\u010cere\u0161","sequence":"additional","affiliation":[{"name":"Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine, Comenius University and University Hospital Martin","place":["Martin, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matej","family":"Vnucak","sequence":"additional","affiliation":[{"name":"Transplant-Nephrology Department, University Hospital Martin","place":["Martin, Slovakia"]},{"name":"Internal Department I, Jessenius Faculty of Medicine, Comenius University and University Hospital Martin","place":["Martin, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol","family":"Granak","sequence":"additional","affiliation":[{"name":"Transplant-Nephrology Department, University Hospital Martin","place":["Martin, Slovakia"]},{"name":"Internal Department I, Jessenius Faculty of Medicine, Comenius University and University Hospital Martin","place":["Martin, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Beck","sequence":"additional","affiliation":[{"name":"Chronix Biomedical GmbH","place":["G\u00f6ttingen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Bornemann-Kolatzki","sequence":"additional","affiliation":[{"name":"Chronix Biomedical GmbH","place":["G\u00f6ttingen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Oellerich","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, George\u2013August University","place":["G\u00f6ttingen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Schuetz","sequence":"additional","affiliation":[{"name":"Chronix Biomedical GmbH","place":["G\u00f6ttingen, Germany"]},{"name":"Insight Molecular Diagnostics","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemens","family":"Budde","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Intensive Care, Charit\u00e9 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2541","DOI":"10.1111\/ajt.13387","article-title":"Cell-free DNA: an upcoming biomarker in transplantation","volume":"15","author":"Gielis","year":"2015","journal-title":"Am J Transplant"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2320","DOI":"10.1038\/s41591-024-03087-3","article-title":"Cell-free DNA for the detection of kidney allograft rejection","volume":"30","author":"Aubert","year":"2024","journal-title":"Nat Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1681\/ASN.2016091034","article-title":"Cell-free DNA and active rejection in kidney allografts","volume":"28","author":"Bloom","year":"2017","journal-title":"J Am Soc 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Transplant","author":"Benning","year":"2026"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1373\/clinchem.2013.210328","article-title":"Digital droplet PCR for rapid quantification of donor DNA in the circulation of transplant recipients as a potential universal biomarker of graft injury","volume":"59","author":"Beck","year":"2013","journal-title":"Clin Chem"}],"container-title":["Frontiers in 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