Molecular Analysis of Renal Allograft Biopsies: Where Do We Stand and Where Are We Going?

A renal core biopsy for histological evaluation is the gold standard for diagnosing renal transplant pathology. However, renal biopsy interpretation is subjective and can render insufficient precision, making it difficult to apply a targeted therapeutic regimen for the individual patient. This warrants a need for additional methods assessing disease state in the renal transplant. Significant research activity has been focused on the role of molecular analysis in the diagnosis of renal allograft rejection. The identification of specific molecular expression patterns in allograft biopsies related to different types of allograft injury could provide valuable information about the processes underlying renal transplant dysfunction and can be used for the development of molecular classifier scores, which could improve our diagnostic and prognostic ability and could guide treatment. Molecular profiling has the potential to be more precise and objective than histological evaluation and may identify injury even before it becomes visible on histology, making it possible to start treatment at the earliest time possible. Combining conventional diagnostics (histology, serology, and clinical data) and molecular evaluation will most likely offer the best diagnostic approach. We believe that the use of state-of-the-art molecular analysis will have a significant impact in diagnostics after renal transplantation. In this review, we elaborate on the molecular phenotype of both acute and chronic T cell-mediated rejection and antibody-mediated rejection and discuss the additive value of molecular profiling in the setting of diagnosing renal allograft rejection and how this will improve transplant patient care.