{"title":"供体来源的无细胞DNA检测在儿童肾移植受者：指征和临床应用。","authors":"Jayanthi Chandar, Vaka Sigurjonsdottir, Marissa Defreitas, Tara Gavcovich, Mingming Zhou, Renata Glehn-Ponsirenas, George Burke","doi":"10.1007/s00467-025-06770-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>We describe our single-center experience in performing donor-derived cell-free DNA (dd-cfDNA) testing for a clinical indication in pediatric kidney transplant recipients.</p><p><strong>Methods: </strong>Dd-cfDNA was done for increase in creatinine, appearance of de novo anti-HLA antibodies (dnHLAab) and for a clinical indication. We compared clinical characteristics of patients with dd-cfDNA > 1 with those with dd-cfDNA ≤ 1 and also compared dd-cfDNA in patients with no biopsy proven rejection (BPAR) or dnHLAab with those with BPAR, and those with dnHLAab and no BPAR.</p><p><strong>Results: </strong>Chart review was performed in 106 patients with a mean age of 11.0 ± 5.5 years. When compared with 62 patients with dd-cfDNA ≤ 1, 59.0% (26/44) of patients with dd-cfDNA > 1 had BPAR (OR 13.5: 95%CI 4.6,38; p < 0.0001), and 88.1% (37/44) had dnHLAab (OR 60.3 95%CI 17.2,192.2; p < 0.0001). Patients with DQ and DR dnHLAab (OR 115.2: 95%CI 24.8, 509.5; p < 0.0001) and those with donor-specific antibodies (DSAs) (OR 50.8: 95%CI 13.0, 168.7; p < 0.0001) were likely to have dd-cfDNA > 1. A repeated measures linear mixed effect model revealed a significant difference in dd-cfDNA between those with no antibodies or BPAR (p < 0.0001) and patients with BPAR and dnHLAab, with or without DSA. At the end of the follow-up period, eGFR was 72 mL/min/1.73 m<sup>2</sup> in those without BPAR or dnHLAab and was significantly different from those with BPAR (eGFR 51 mL/min/1.73 m<sup>2</sup> (p < 0.0001).</p><p><strong>Conclusions: </strong>Elevated dd-cfDNA is strongly associated with BPAR, class II dnHLAab and DSAs. Conversely, low values are observed in immunoquiescent states. Dd-cfDNA can be a useful tool for non-invasive clinical decision-making.</p>","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Donor-derived cell-free DNA testing in pediatric kidney transplant recipients: indications and clinical utility.\",\"authors\":\"Jayanthi Chandar, Vaka Sigurjonsdottir, Marissa Defreitas, Tara Gavcovich, Mingming Zhou, Renata Glehn-Ponsirenas, George Burke\",\"doi\":\"10.1007/s00467-025-06770-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>We describe our single-center experience in performing donor-derived cell-free DNA (dd-cfDNA) testing for a clinical indication in pediatric kidney transplant recipients.</p><p><strong>Methods: </strong>Dd-cfDNA was done for increase in creatinine, appearance of de novo anti-HLA antibodies (dnHLAab) and for a clinical indication. We compared clinical characteristics of patients with dd-cfDNA > 1 with those with dd-cfDNA ≤ 1 and also compared dd-cfDNA in patients with no biopsy proven rejection (BPAR) or dnHLAab with those with BPAR, and those with dnHLAab and no BPAR.</p><p><strong>Results: </strong>Chart review was performed in 106 patients with a mean age of 11.0 ± 5.5 years. When compared with 62 patients with dd-cfDNA ≤ 1, 59.0% (26/44) of patients with dd-cfDNA > 1 had BPAR (OR 13.5: 95%CI 4.6,38; p < 0.0001), and 88.1% (37/44) had dnHLAab (OR 60.3 95%CI 17.2,192.2; p < 0.0001). Patients with DQ and DR dnHLAab (OR 115.2: 95%CI 24.8, 509.5; p < 0.0001) and those with donor-specific antibodies (DSAs) (OR 50.8: 95%CI 13.0, 168.7; p < 0.0001) were likely to have dd-cfDNA > 1. A repeated measures linear mixed effect model revealed a significant difference in dd-cfDNA between those with no antibodies or BPAR (p < 0.0001) and patients with BPAR and dnHLAab, with or without DSA. At the end of the follow-up period, eGFR was 72 mL/min/1.73 m<sup>2</sup> in those without BPAR or dnHLAab and was significantly different from those with BPAR (eGFR 51 mL/min/1.73 m<sup>2</sup> (p < 0.0001).</p><p><strong>Conclusions: </strong>Elevated dd-cfDNA is strongly associated with BPAR, class II dnHLAab and DSAs. Conversely, low values are observed in immunoquiescent states. Dd-cfDNA can be a useful tool for non-invasive clinical decision-making.</p>\",\"PeriodicalId\":19735,\"journal\":{\"name\":\"Pediatric Nephrology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-04-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Nephrology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00467-025-06770-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00467-025-06770-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
Donor-derived cell-free DNA testing in pediatric kidney transplant recipients: indications and clinical utility.
Background: We describe our single-center experience in performing donor-derived cell-free DNA (dd-cfDNA) testing for a clinical indication in pediatric kidney transplant recipients.
Methods: Dd-cfDNA was done for increase in creatinine, appearance of de novo anti-HLA antibodies (dnHLAab) and for a clinical indication. We compared clinical characteristics of patients with dd-cfDNA > 1 with those with dd-cfDNA ≤ 1 and also compared dd-cfDNA in patients with no biopsy proven rejection (BPAR) or dnHLAab with those with BPAR, and those with dnHLAab and no BPAR.
Results: Chart review was performed in 106 patients with a mean age of 11.0 ± 5.5 years. When compared with 62 patients with dd-cfDNA ≤ 1, 59.0% (26/44) of patients with dd-cfDNA > 1 had BPAR (OR 13.5: 95%CI 4.6,38; p < 0.0001), and 88.1% (37/44) had dnHLAab (OR 60.3 95%CI 17.2,192.2; p < 0.0001). Patients with DQ and DR dnHLAab (OR 115.2: 95%CI 24.8, 509.5; p < 0.0001) and those with donor-specific antibodies (DSAs) (OR 50.8: 95%CI 13.0, 168.7; p < 0.0001) were likely to have dd-cfDNA > 1. A repeated measures linear mixed effect model revealed a significant difference in dd-cfDNA between those with no antibodies or BPAR (p < 0.0001) and patients with BPAR and dnHLAab, with or without DSA. At the end of the follow-up period, eGFR was 72 mL/min/1.73 m2 in those without BPAR or dnHLAab and was significantly different from those with BPAR (eGFR 51 mL/min/1.73 m2 (p < 0.0001).
Conclusions: Elevated dd-cfDNA is strongly associated with BPAR, class II dnHLAab and DSAs. Conversely, low values are observed in immunoquiescent states. Dd-cfDNA can be a useful tool for non-invasive clinical decision-making.
期刊介绍：
International Pediatric Nephrology Association
Pediatric Nephrology publishes original clinical research related to acute and chronic diseases that affect renal function, blood pressure, and fluid and electrolyte disorders in children. Studies may involve medical, surgical, nutritional, physiologic, biochemical, genetic, pathologic or immunologic aspects of disease, imaging techniques or consequences of acute or chronic kidney disease. There are 12 issues per year that contain Editorial Commentaries, Reviews, Educational Reviews, Original Articles, Brief Reports, Rapid Communications, Clinical Quizzes, and Letters to the Editors.
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