Improving the histologic detection of donor-specific antibody-negative antibody-mediated rejection in kidney transplants
Recommended Citation
Hidalgo LG, Madill-Thomsen KS, Reeve J, Mackova M, Gauthier P, Demko Z, Prewett A, Lee M, Alhamad T, Anand S, Arnol M, Baliga R, Banasik M, Blosser CD, Bobba S, Brennan D, Bromberg J, Budde K, Chamienia A, Chow K, Ciszek M, Costa N, Dęborska-Materkowska D, Debska-Ślizień A, Domański L, Fatica R, Francis I, Fryc J, Gill J, Gill J, Glyda M, Gourishankar S, Gryczman M, Gupta G, Hruba P, Hughes P, Jittirat A, Jurekovic Z, Kamal L, Kamel M, Kant S, Kojc N, Konopa J, Kumar D, Lan J, Lowe D, Mazurkiewicz J, Miglinas M, Moinuddin I, Mueller T, Myślak M, Naumnik B, Pączek L, Patel A, Perkowska-Ptasińska A, Piecha G, Poggio E, Bloudíčkova SR, Regele H, Schachtner T, Shojai S, Sikosana MLN, Slatinská J, Smykal-Jankowiak K, Haler Ž V, Viklicky O, Vucur K, Weir MR, Wiecek A, Zaky Z, and Halloran PF. Improving the histologic detection of donor-specific antibody-negative antibody-mediated rejection in kidney transplants. Am J Transplant 2025.
Document Type
Article
Publication Date
8-23-2025
Publication Title
American journal of transplantation
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 3 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 the detection of DSA-negative ABMR. However, simply calling all DSA as positive allowed the Banff 2022 guidelines to identify 46% more ABMR cases with no measurable conventional 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. Trifecta-Kidney Study ClinicalTrials.gov #NCT04239703.
PubMed ID
40854490
ePublication
ePub ahead of print
