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.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: We studied the variation in molecular T cell-mediated rejection (TCMR) activity in kidney transplant indication biopsies and its relationship with histologic lesions (particularly tubulitis and atrophy-fibrosis) and time posttransplant. METHODS: We examined 175 kidney transplant biopsies with molecular TCMR as defined by archetypal analysis in the INTERCOMEX study ( ClinicalTrials.gov #NCT01299168). TCMR activity was defined by a molecular classifier. RESULTS: Archetypal analysis identified 2 TCMR classes, TCMR1 and TCMR2: TCMR1 had higher TCMR activity and more antibody-mediated rejection ("mixed") activity and arteritis but little hyalinosis, whereas TCMR2 had less TCMR activity but more atrophy-fibrosis. TCMR1 and TCMR2 had similar levels of molecular injury and tubulitis. Both TCMR1 and TCMR2 biopsies were uncommon after 2 y posttransplant and were rare after 10 y, particularly TCMR1. Within late TCMR biopsies, TCMR classifier activity and activity molecules such as IFNG fell progressively with time, but tubulitis and molecular injury were sustained. Atrophy-fibrosis was increased in TCMR biopsies, even in the first year posttransplant, and rose with time posttransplant. TCMR1 and TCMR2 both reduced graft survival, but in random forests, the strongest determinant of survival after biopsies with TCMR was molecular injury, not TCMR activity. CONCLUSIONS: TCMR varies in intensity but is always strongly related to molecular injury and atrophy-fibrosis, which ultimately explains its effect on survival. We hypothesize, based on the reciprocal relationship with hyalinosis, that the TCMR1-TCMR2 gradient reflects calcineurin inhibitor drug underexposure, whereas the time-dependent decline in TCMR activity and frequency after the first year reflects T-cell exhaustion.

• MeSH
• atrofie patologie   MeSH
• biopsie MeSH
• fibróza MeSH
• lidé MeSH
• rejekce štěpu patologie   MeSH
• T-lymfocyty MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH