| Title: | Improving the histologic detection of DSA-negative antibody-mediated rejection in kidney transplants |
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| Authors: | ID Hidalgo, Luis G. (Author)
ID Madill-Thomsen, Katelynn (Author)
ID Reeve, Jeff (Author)
ID Mackova, Martina (Author)
ID Gauthier, Philippe (Author)
ID Demko, Zachary (Author)
ID Prewett, Adam (Author)
ID Arnol, Miha (Author)
ID Kojc, Nika (Author)
ID Večerić-Haler, Željka (Author), et al. |
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| Files: |  PDF - Presentation file, download (2,47 MB)
MD5: 945050CA962CDA9C441E173C598C5771
 URL - Source URL, visit https://www.amjtransplant.org/article/S1600-6135(25)02943-0/
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKC LJ - Ljubljana University Medical Centre
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| Abstract: | Emerging treatments for antibody-mediated rejection (ABMR, NEJM391(2):122-132) have increased the importance of ABMR detection when donor-specific antibody (DSA) is negative. We addressed this issue in the Trifecta-Kidney study (ClinicalTrials.gov #NCT04239703) using three centralized tests in 690 kidney transplant biopsies: DSA (One Lambda Inc.), blood donor-derived cell-free DNA (dd-cfDNA, Prospera™ test, Natera, Inc.), and molecular biopsy assessment (MMDx). We used an “AutoBanff 2022” algorithm to model the impact of alternative DSA interpretations on the histologic diagnosis of “DSA-negative” ABMR following Banff guidelines, including agreement with dd-cfDNA and molecular ABMR. Lowering MFI cutoffs for DSA-positivity did not improve detection of DSA-negative ABMR. However, simply calling all DSA positive allowed Banff 2022 guidelines to identify 46% more ABMR cases with no measurable DSA, and per Net Reclassification Improvement increased agreement between histologic diagnoses and both dd-cfDNA (P=7.72E-7) and molecular ABMR (P=7.69E-7). New ABMR cases were as strongly positive for dd-cfDNA and molecular ABMR as those found using the conventional DSA interpretation. A validation set analysis using INTERCOMEX study data (ClinicalTrials.gov NCT#01299168) confirmed these findings, and found that the new DSA-negative ABMR cases identified by calling all DSA positive had the same risk for graft loss as those found with conventional DSA interpretation. |
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| Keywords: | donor-derived cell-free DNA, kidney biopsy, donor-specific antibody, microarrays antibody-mediated rejection, kidney transplant rejection |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2026 |
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| Number of pages: | str. 117-130 |
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| Numbering: | Vol. 26, iss. 1 |
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| PID: | 20.500.12556/DiRROS-25171  |
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| UDC: | 616.61 |
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| ISSN on article: | 1600-6143 |
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| DOI: | 10.1016/j.ajt.2025.08.029 |
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| COBISS.SI-ID: | 246735107 |
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| Note: | Nasl. z nasl. zaslona;
Opis vira z dne 27. 8. 2025;
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| Publication date in DiRROS: | 13.01.2026 |
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| Views: | 244 |
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| Downloads: | 78 |
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