Elena Cuadrado-Payán , Eva González-Roca , Diana Rodríguez-Espinosa , Alicia Molina-Andújar , Enrique Montagud-Marrahi , Carolt Arana , Angela González-Rojas , Nuria Esforzado , Vicens Torregrosa , Pedro Ventura-Aguiar , María Argudo , Daniel Serrano-Jorcano , Maria José Ramírez-Bajo , Elisenda Bañón-Maneus , Silvia Casas , José Jesus Broseta , Joan Anton Puig-Butille , Ignacio Revuelta , Fritz Diekmann , David Cucchiari
{"title":"在日常临床实践中测定供体来源无细胞DNA的内部技术的实施：来自巴塞罗那医院诊所的经验","authors":"Elena Cuadrado-Payán , Eva González-Roca , Diana Rodríguez-Espinosa , Alicia Molina-Andújar , Enrique Montagud-Marrahi , Carolt Arana , Angela González-Rojas , Nuria Esforzado , Vicens Torregrosa , Pedro Ventura-Aguiar , María Argudo , Daniel Serrano-Jorcano , Maria José Ramírez-Bajo , Elisenda Bañón-Maneus , Silvia Casas , José Jesus Broseta , Joan Anton Puig-Butille , Ignacio Revuelta , Fritz Diekmann , David Cucchiari","doi":"10.1016/j.nefroe.2025.03.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and objective</h3><div>The introduction of donor-derived free DNA (ddcfDNA) has emerged as an accurate non-invasive biomarker to diagnose rejection, compared to classical ones. Here we evaluate our experience after its implementation in our center as an in-house technique.</div></div><div><h3>Materials and methods</h3><div>Single-center cross-sectional study with extraction of cell-free DNA in blood and quantification of the ddcfDNA using the AlloSeqcfDNA assay (CareDx) at the time of performing biopsies ‘per protocol’ or ‘per indication’ between December 2020 and December 2023.</div></div><div><h3>Results</h3><div>172 graft biopsies were included (59 for protocol and 113 for cause) in 112 kidney transplant recipients. Among the biopsies, 19 borderline rejections, 11 T-cell mediated rejections, and 30 antibody-mediated rejections were identified. The median ddcfDNA in each diagnostic group was: 0.40% (0.23%–0.82%) in borderline, 0.60% (0.23%–1.91%) in cellular, and 1.48% (0.77%–3.4%) in antibody-mediated rejection (<em>P</em> < .001). In the 112 biopsies with no signs of rejection, the median ddcfDNA was 0.33% (0.17%–0.54%) (<em>P</em> < .001). Cases with positive DSAs and rejection showed higher levels of ddcfDNA than positive DSAs without rejection (<em>P</em> = .010), and ddcfDNA levels were significantly associated with microvascular inflammation and C4d positivity. The area under the ROC curves of ddcfDNA to discriminate any type of rejection from the absence of rejection was 0.74 (0.65−0.82) and, excluding borderline rejection from the analysis, 0.80 (0.72−0.89), outperforming other markers of renal function.</div></div><div><h3>Conclusions</h3><div>Implementing ddcfDNA analysis at our center as a clinical tool has proven valuable for distinguishing biopsy-confirmed acute rejection, particularly antibody-mediated rejection, outperforming classic renal function markers. Its hospital-based implementation supports timely and accurate diagnosis, improving transplant management and prognosis.</div></div>","PeriodicalId":31770,"journal":{"name":"Nefrologia English Edition","volume":"45 4","pages":"Pages 294-301"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Implementation of the in-house technique for the determination of donor-derived cell-free DNA in daily clinical practice: Experience from the Hospital Clinic of Barcelona\",\"authors\":\"Elena Cuadrado-Payán , Eva González-Roca , Diana Rodríguez-Espinosa , Alicia Molina-Andújar , Enrique Montagud-Marrahi , Carolt Arana , Angela González-Rojas , Nuria Esforzado , Vicens Torregrosa , Pedro Ventura-Aguiar , María Argudo , Daniel Serrano-Jorcano , Maria José Ramírez-Bajo , Elisenda Bañón-Maneus , Silvia Casas , José Jesus Broseta , Joan Anton Puig-Butille , Ignacio Revuelta , Fritz Diekmann , David Cucchiari\",\"doi\":\"10.1016/j.nefroe.2025.03.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and objective</h3><div>The introduction of donor-derived free DNA (ddcfDNA) has emerged as an accurate non-invasive biomarker to diagnose rejection, compared to classical ones. Here we evaluate our experience after its implementation in our center as an in-house technique.</div></div><div><h3>Materials and methods</h3><div>Single-center cross-sectional study with extraction of cell-free DNA in blood and quantification of the ddcfDNA using the AlloSeqcfDNA assay (CareDx) at the time of performing biopsies ‘per protocol’ or ‘per indication’ between December 2020 and December 2023.</div></div><div><h3>Results</h3><div>172 graft biopsies were included (59 for protocol and 113 for cause) in 112 kidney transplant recipients. Among the biopsies, 19 borderline rejections, 11 T-cell mediated rejections, and 30 antibody-mediated rejections were identified. The median ddcfDNA in each diagnostic group was: 0.40% (0.23%–0.82%) in borderline, 0.60% (0.23%–1.91%) in cellular, and 1.48% (0.77%–3.4%) in antibody-mediated rejection (<em>P</em> < .001). In the 112 biopsies with no signs of rejection, the median ddcfDNA was 0.33% (0.17%–0.54%) (<em>P</em> < .001). Cases with positive DSAs and rejection showed higher levels of ddcfDNA than positive DSAs without rejection (<em>P</em> = .010), and ddcfDNA levels were significantly associated with microvascular inflammation and C4d positivity. The area under the ROC curves of ddcfDNA to discriminate any type of rejection from the absence of rejection was 0.74 (0.65−0.82) and, excluding borderline rejection from the analysis, 0.80 (0.72−0.89), outperforming other markers of renal function.</div></div><div><h3>Conclusions</h3><div>Implementing ddcfDNA analysis at our center as a clinical tool has proven valuable for distinguishing biopsy-confirmed acute rejection, particularly antibody-mediated rejection, outperforming classic renal function markers. Its hospital-based implementation supports timely and accurate diagnosis, improving transplant management and prognosis.</div></div>\",\"PeriodicalId\":31770,\"journal\":{\"name\":\"Nefrologia English Edition\",\"volume\":\"45 4\",\"pages\":\"Pages 294-301\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nefrologia English Edition\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2013251425000483\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nefrologia English Edition","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2013251425000483","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Implementation of the in-house technique for the determination of donor-derived cell-free DNA in daily clinical practice: Experience from the Hospital Clinic of Barcelona
Background and objective
The introduction of donor-derived free DNA (ddcfDNA) has emerged as an accurate non-invasive biomarker to diagnose rejection, compared to classical ones. Here we evaluate our experience after its implementation in our center as an in-house technique.
Materials and methods
Single-center cross-sectional study with extraction of cell-free DNA in blood and quantification of the ddcfDNA using the AlloSeqcfDNA assay (CareDx) at the time of performing biopsies ‘per protocol’ or ‘per indication’ between December 2020 and December 2023.
Results
172 graft biopsies were included (59 for protocol and 113 for cause) in 112 kidney transplant recipients. Among the biopsies, 19 borderline rejections, 11 T-cell mediated rejections, and 30 antibody-mediated rejections were identified. The median ddcfDNA in each diagnostic group was: 0.40% (0.23%–0.82%) in borderline, 0.60% (0.23%–1.91%) in cellular, and 1.48% (0.77%–3.4%) in antibody-mediated rejection (P < .001). In the 112 biopsies with no signs of rejection, the median ddcfDNA was 0.33% (0.17%–0.54%) (P < .001). Cases with positive DSAs and rejection showed higher levels of ddcfDNA than positive DSAs without rejection (P = .010), and ddcfDNA levels were significantly associated with microvascular inflammation and C4d positivity. The area under the ROC curves of ddcfDNA to discriminate any type of rejection from the absence of rejection was 0.74 (0.65−0.82) and, excluding borderline rejection from the analysis, 0.80 (0.72−0.89), outperforming other markers of renal function.
Conclusions
Implementing ddcfDNA analysis at our center as a clinical tool has proven valuable for distinguishing biopsy-confirmed acute rejection, particularly antibody-mediated rejection, outperforming classic renal function markers. Its hospital-based implementation supports timely and accurate diagnosis, improving transplant management and prognosis.
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