Systematic Biopsy-Based Transcriptomics and Diagnosis of Antibody-Mediated Kidney Transplant Rejection in Clinical Practice

BACKGROUND:To diagnose kidney transplant antibody-mediated rejection, biopsy-based transcriptomics can substitute for some histological criteria according to the Banff classification. However, clinical accessibility of these assays is still limited. Here, we aimed to evaluate the impact of integrating a routine-compatible molecular assay for the diagnosis of antibody-mediated rejection in clinical practice. METHODS:All biopsies performed in our center between 2013 and 2017 were retrospectively included. These biopsies were classified into three groups: "Antibody-mediated rejection biopsies" which displayed the full Banff criteria of antibody-mediated rejection independently of biopsy-based transcriptomics; "Undetermined for antibody-mediated rejection" biopsies which did not meet antibody-mediated rejection histological criteria, but would have been considered as antibody-mediated rejection if biopsy-based transcriptomics had been positive; and control biopsies which showed no features of rejection. RESULTS:Within the inclusion period, 342 biopsies had a complete Banff scoring. Thirty-six of the biopsies already met antibody-mediated rejection criteria, and 43 out of 306 (14%) were considered as "undetermined for antibody-mediated rejection." Among these biopsies, 24 out of 43 (56%) had a molecular signature of antibody-mediated rejection, reclassifying them into the "antibody-mediated rejection" category. Five-year death-censored survival of these biopsies was unfavorable and statistically equivalent to that of the "antibody-mediated rejection" category (p = 0.22), with 15 out of 24 (63%) graft loss. CONCLUSION:A significant proportion of biopsies could benefit from a biopsy-based transcriptomics for antibody-mediated rejection diagnosis according to the Banff classification. Using a routine-compatible molecular tool, more than the half of these biopsies were reclassified as antibody-mediated rejection and associated with poor allograft survival.