Intercenter Variability in the Application of Biopsy-based Transcriptomics in Kidney Transplantation

Area of Science:

• Nephrology
• Transplant Immunology
• Molecular Diagnostics

Background:

• Biopsy-based transcriptomics (BBT) was introduced in Central Europe in 2022 to enhance kidney transplant diagnostics.
• Significant variations in diagnostic practices among transplant centers using BBT require further investigation.

Purpose of the Study:

• To evaluate differences in BBT indications across transplant centers.
• To assess discrepancies between traditional histology and BBT (MMDx) results in kidney graft biopsies.
• To analyze the impact of center volume on diagnostic concordance.

Main Methods:

• Retrospective analysis of 474 kidney graft biopsies from 10 centers (August 2022 - May 2024).
• Simultaneous application of routine histology and BBT using the Molecular Microscope Diagnostic System (MMDx).
• Evaluation of Banff 2022 histology criteria against MMDx findings and assessment of center-specific BBT utilization patterns.

Main Results:

• BBT was utilized in only 12%-31% of biopsies, with histology dominating diagnostic decisions.
• Significant variability in BBT indications, including cases with histological no-rejection, chronic AMR, and borderline changes.
• Moderate agreement between BBT and histology (κ = 0.49), with molecular AMR detected in 10-77% of specific histological categories and molecular TCMR in 9-26% of cases.
• Discrepancy rates were similar between high- and low-volume centers.

Conclusions:

• A moderate level of discrepancy exists between histology and MMDx results, irrespective of transplant center volume.
• The indications for employing BBT in kidney transplant diagnostics are highly variable across centers.
• Standardized indications for BBT are necessary to effectively integrate molecular diagnostics into routine clinical practice.