Systematic biopsy-based transcriptomics and diagnosis of antibody-mediated kidney transplant rejection in clinical practice

Key Points Impact of biopsy-based transcriptomics in clinical practice is still unclear. Biopsy-based transcriptomics is indicated in a significant proportion of kidney transplant biopsies for the diagnosis of antibody-mediated rejection. Biopsy-based transcriptomics is useful for antibody-mediated rejection diagnosis in clinical practice. Background To diagnose kidney transplant antibody-mediated rejection (AMR), 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 AMR in clinical practice. Methods All biopsies performed in our center between 2013 and 2017 were retrospectively included. These biopsies were classified into three groups: AMR biopsies which displayed the full Banff criteria of AMR independently of biopsy-based transcriptomics; undetermined for AMR biopsies which did not meet AMR histological criteria, but would have been considered as AMR 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 AMR criteria, and 43 of 306 (14%) were considered as undetermined for AMR. Among these biopsies, 24 of 43 (56%) had a molecular signature of AMR, reclassifying them into the AMR category. Five-year death-censored survival of these biopsies was unfavorable and statistically equivalent to that of the AMR category ( P = 0.22), with 15 of 24 (63%) graft loss. Conclusions A significant proportion of biopsies could benefit from a biopsy-based transcriptomics for AMR diagnosis according to the Banff classification. Using a routine-compatible molecular tool, more than the half of these biopsies were reclassified as AMR and associated with poor allograft survival.