Improving the histologic detection of DSA-negative antibody-mediated rejection in kidney transplants

Hidalgo, Luis G. (author), Arnol, Miha (author), Kojc, Nika (author), Večerić-Haler, Željka (author), Halloran, Philip F (author)

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.

• Language: English
• Keywords: donor-derived cell-free DNA, kidney biopsy, donor-specific antibody, microarrays antibody-mediated rejection, kidney transplant rejection
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: Str. 117-130
• Numbering: Vol. 26, iss. 1
• PID: 20.500.12556/RUL-181417
• UDC: 616.61
• ISSN on article: 1600-6143
• DOI: 10.1016/j.ajt.2025.08.029
• COBISS.SI-ID: 246735107
• Publication date in RUL: 07.04.2026

Record is a part of a journal

• Title: American journal of transplantation
• Shortened title: Am. j. transplant.
• Publisher: Elsevier, American Society of Transplantation & American Society of Transplant Surgeons
• ISSN: 1600-6143
• COBISS.SI-ID: 24071897

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• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
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