Promises and limits of biopsy-based transcriptomics in kidney transplantation: a clinical utility perspective

Biopsy-based transcriptomics have been proposed as a complement to histopathology in the evaluation of kidney allograft rejection by providing standardized, mechanism-oriented insight into intra-graft immune activity. However, diagnostic performance, interpretability, and clinical relevance vary substantially across rejection phenotypes and clinical contexts. This review critically examines the evidence supporting biopsy-based transcriptomics and evaluates where, and whether, it adds value to practice.

Large multicenter studies show that biopsy-based transcriptomics achieve robust analytical performance for antibody-mediated rejection. In contrast, for T cell-mediated rejection, intermediate Banff phenotypes, mixed rejection, and molecular activity detected in histologically negative biopsies, transcriptomic signals are more heterogeneous and frequently discordant with histology. Associations with graft outcome and treatment response have been reported but are largely derived from observational cohorts and lack validated, phenotype-specific thresholds. To date, no interventional studies have demonstrated improved patient outcomes through molecularly guided management.

Biopsy-based transcriptomics provides biologically meaningful information but has not yet demonstrated outcome-improving clinical utility. Its value is highly context- dependent and currently best defined for selected scenarios rather than routine use. Prospective interventional studies and consensus-based interpretative frameworks are required to determine how molecular information should inform clinical decision-making in kidney transplantation.