Blood transcriptomics as non-invasive marker for kidney transplant rejection.

In the last decade, a plenitude of potential molecular peripheral blood biomarkers has been developed. In assessing the utility of these markers for clinical practice, it is important to evaluate their diagnostic performance in different clinical scenarios. The higher probability of diagnosing rejection in indication compared to protocol biopsies illustrates that kidney functional parameters (estimated glomerular filtration rate evolution, proteinuria) are inherently already non-invasive biomarkers for rejection, with evident clinical utility. However, by definition, graft functional assessment will miss subclinical rejection. In this paper, we review how some of the most promising peripheral blood molecular biomarkers, like blood transcriptomic markers and donor-derived cell-free DNA measurement, perform in relation to graft functional evaluation. Since the definition of graft dysfunction is relatively arbitrary, we propose using a standardized clinical model for non-invasive diagnosis of allograft rejection, as benchmark and for integration with novel molecular biomarkers.