Assessment of Donor Derived Cell Free DNA (dd-cfDNA) at Surveillance and at Clinical Suspicion of Acute Rejection in Renal Transplantation
In our prospective, unicenter cohort study, we collected blood samples from 30 newly kidney transplanted patients, at month 1, 2, 3, and 5 for dd-cfDNA analysis, along with creatinine/eGFR and DSA monitoring, and from 32 patients who underwent an indication biopsy and whose dd-cfDNA levels were meas...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Transplant International |
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| Online Access: | https://www.frontierspartnerships.org/articles/10.3389/ti.2023.11507/full |
| _version_ | 1827292211698466816 |
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| author | Evangelos Mantios Vassilis Filiopoulos Pantelis Constantoulakis George Liapis Angeliki Vittoraki Silvia Casas Smaragdi Marinaki John N Boletis |
| author_facet | Evangelos Mantios Vassilis Filiopoulos Pantelis Constantoulakis George Liapis Angeliki Vittoraki Silvia Casas Smaragdi Marinaki John N Boletis |
| author_sort | Evangelos Mantios |
| collection | DOAJ |
| description | In our prospective, unicenter cohort study, we collected blood samples from 30 newly kidney transplanted patients, at month 1, 2, 3, and 5 for dd-cfDNA analysis, along with creatinine/eGFR and DSA monitoring, and from 32 patients who underwent an indication biopsy and whose dd-cfDNA levels were measured at the time of biopsy and 1 month afterwards. Fourteen of 32 (43.8%) patients in the biopsy group were diagnosed with TCMR and 5 of 32 (15.6%) with ABMR. Dd-cfDNA proved to be better than creatinine in diagnosing rejection from non-rejection in patients who were biopsied. When a dd-cfDNA threshold of 0.5% was chosen, sensitivity was 73.7% and specificity was 92.3% (AUC: 0.804, 0.646–0.961). In rejection patients, levels of dd-cfDNA prior to biopsy (0.94%, 0.3–2.0) decreased substantially after initiation of treatment with median returning to baseline already at 1 month (0.33%, 0.21–0.51, p = 0.0036). In the surveillance group, high levels of dd-cfDNA (>0.5%) from second month post-transplantation were correlated with non-increasing eGFR 1 year post-transplantation. The study used AlloSeq kit for kidney transplant surveillance for first time and confirmed dd-cfDNA’s ability to detect rejection and monitor treatment, as well as to predict worse long-term outcomes regarding eGFR. |
| first_indexed | 2024-04-24T12:59:10Z |
| format | Article |
| id | doaj.art-ece47506b29b44939e1c3d6e771034bd |
| institution | Directory Open Access Journal |
| issn | 1432-2277 |
| language | English |
| last_indexed | 2024-04-24T12:59:10Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Transplant International |
| spelling | doaj.art-ece47506b29b44939e1c3d6e771034bd2024-04-05T16:44:43ZengFrontiers Media S.A.Transplant International1432-22772023-10-013610.3389/ti.2023.1150711507Assessment of Donor Derived Cell Free DNA (dd-cfDNA) at Surveillance and at Clinical Suspicion of Acute Rejection in Renal TransplantationEvangelos Mantios0Vassilis Filiopoulos1Pantelis Constantoulakis2George Liapis3Angeliki Vittoraki4Silvia Casas5Smaragdi Marinaki6John N Boletis7Department of Nephrology and Kidney Transplantation, School of Medicine, General Hospital of Athens Laiko, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Nephrology and Kidney Transplantation, School of Medicine, General Hospital of Athens Laiko, National and Kapodistrian University of Athens, Athens, Greece“Genotypos” Science Laboratory of Molecular Genetic and Cytogenetics, Athens, GreecePathology Department, School of Medicine, General Hospital of Athens Laiko, National and Kapodistrian University of Athens, Athens, GreeceImmunology Department, National Tissue Typing Center, General Hospital of Athens “G. Gennimatas”, Athens, GreeceCareDx Inc., Brisbane, CA, United StatesDepartment of Nephrology and Kidney Transplantation, School of Medicine, General Hospital of Athens Laiko, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Nephrology and Kidney Transplantation, School of Medicine, General Hospital of Athens Laiko, National and Kapodistrian University of Athens, Athens, GreeceIn our prospective, unicenter cohort study, we collected blood samples from 30 newly kidney transplanted patients, at month 1, 2, 3, and 5 for dd-cfDNA analysis, along with creatinine/eGFR and DSA monitoring, and from 32 patients who underwent an indication biopsy and whose dd-cfDNA levels were measured at the time of biopsy and 1 month afterwards. Fourteen of 32 (43.8%) patients in the biopsy group were diagnosed with TCMR and 5 of 32 (15.6%) with ABMR. Dd-cfDNA proved to be better than creatinine in diagnosing rejection from non-rejection in patients who were biopsied. When a dd-cfDNA threshold of 0.5% was chosen, sensitivity was 73.7% and specificity was 92.3% (AUC: 0.804, 0.646–0.961). In rejection patients, levels of dd-cfDNA prior to biopsy (0.94%, 0.3–2.0) decreased substantially after initiation of treatment with median returning to baseline already at 1 month (0.33%, 0.21–0.51, p = 0.0036). In the surveillance group, high levels of dd-cfDNA (>0.5%) from second month post-transplantation were correlated with non-increasing eGFR 1 year post-transplantation. The study used AlloSeq kit for kidney transplant surveillance for first time and confirmed dd-cfDNA’s ability to detect rejection and monitor treatment, as well as to predict worse long-term outcomes regarding eGFR.https://www.frontierspartnerships.org/articles/10.3389/ti.2023.11507/fulldd-cfDNAkidney allografttransplantationrejectionbiomarker |
| spellingShingle | Evangelos Mantios Vassilis Filiopoulos Pantelis Constantoulakis George Liapis Angeliki Vittoraki Silvia Casas Smaragdi Marinaki John N Boletis Assessment of Donor Derived Cell Free DNA (dd-cfDNA) at Surveillance and at Clinical Suspicion of Acute Rejection in Renal Transplantation Transplant International dd-cfDNA kidney allograft transplantation rejection biomarker |
| title | Assessment of Donor Derived Cell Free DNA (dd-cfDNA) at Surveillance and at Clinical Suspicion of Acute Rejection in Renal Transplantation |
| title_full | Assessment of Donor Derived Cell Free DNA (dd-cfDNA) at Surveillance and at Clinical Suspicion of Acute Rejection in Renal Transplantation |
| title_fullStr | Assessment of Donor Derived Cell Free DNA (dd-cfDNA) at Surveillance and at Clinical Suspicion of Acute Rejection in Renal Transplantation |
| title_full_unstemmed | Assessment of Donor Derived Cell Free DNA (dd-cfDNA) at Surveillance and at Clinical Suspicion of Acute Rejection in Renal Transplantation |
| title_short | Assessment of Donor Derived Cell Free DNA (dd-cfDNA) at Surveillance and at Clinical Suspicion of Acute Rejection in Renal Transplantation |
| title_sort | assessment of donor derived cell free dna dd cfdna at surveillance and at clinical suspicion of acute rejection in renal transplantation |
| topic | dd-cfDNA kidney allograft transplantation rejection biomarker |
| url | https://www.frontierspartnerships.org/articles/10.3389/ti.2023.11507/full |
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