BACKGROUND: Biopsy-based transcriptomics (BBT) was implemented in Central Europe in 2022 to improve kidney transplant diagnostics. Differences in diagnostic practices across transplant centers remain underexplored. METHODS: This retrospective multicenter study analyzed 474 kidney graft biopsies from 10 transplant centers between August 2022 and May 2024, where, besides routine histology, BBT using the Molecular Microscope Diagnostic System (MMDx) was performed. Differences in BBT indications and discrepancies between histology assessment by Banff 2022 and MMDx sign-outs among transplant centers were evaluated. RESULTS: Most centers used BBT in only 12%-31% of all performed biopsies, relying on histology alone for most diagnostic decisions. BBT indications varied across centers: 3 focused on histological no-rejection with clinical discrepancy (44%, 45%, and 70%), 2 on chronic or chronic-active antibody-mediated rejection (AMR; clinical discrepancy 44% and 48%), and 2 on borderline changes (clinical discrepancy 30% and 33%). BBT showed moderate agreement with histology (κ = 0.49), with similar discrepancy rates between high- and low-volume centers. Molecular AMR was found in 44% of probable AMR, 63% of active AMR, 63% of microvascular inflammation, C4d- and donor-specific antibody (DSA)-, 77% of chronic-active AMR, and 21% chronic AMR. Molecular T cell-mediated rejection (TCMR) was confirmed in 26% of histologically active TCMR, in 9% of chronic TCMR, and in 16% of borderline changes. In histologic no-rejection cases, molecular AMR was present in 10% of DSA- and 34% of DSA+ biopsies. CONCLUSIONS: A moderate discrepancy between histology and MMDx sign-outs was found regardless of the center volume. BBT indications notably varied among centers. Standardized indications should be defined to improve the integration of molecular diagnostics into routine care.

3rd Department of Internal Medicine Nephrology Rheumatology and Endocrinology Faculty of Medicine and Dentistry University Hospital Olomouc Czech Republic

Department of Clinical and Transplant Pathology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Internal Medicine and Cardiology University Hospital Ostrava Ostrava Czech Republic

Department of Nephrology and Kidney Transplantations University Hospital Bratislava Faculty of Medicine Comenius University Bratislava Slovakia

Department of Nephrology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Nephrology University Hospital Hradec Kralove Hradec Kralove Czech Republic

Department of Nephrology University Hospital Pilsen Pilsen Czech Republic

Department of Pediatrics 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Transplantation and Nephrology University Hospital Martin and Jessenius Faculty of Medicine Comenius University Martin Slovakia

Department of Transplantation Louis Pasteur University Hospital Kosice Slovakia

F D Roosevelt University Hospital with Policlinic Banská Bystrica Banská Bystrica Slovakia

Transplant Laboratory Institute for Clinical and Experimental Medicine Prague Czech Republic

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