Non-invasive approaches to detect kidney graft injury and distinguish donor-specific immune-mediated injury from other causes of inflammation are needed to guide recipient therapy while avoiding the morbidities of transplant biopsies. We used a multi-plex platform to interrogate RNA isolated from kidney transplant recipient urine to investigate gene expression patterns distinguishing grafts with no injury vs. ongoing injury and further differentiate acute T cell-mediated rejection (TCMR) from BK virus nephropathy (BKVN). As a training set we quantified expression of 796 immune function genes from 25 control recipients with stable graft function, 17 with biopsy-proven acute TCMR, and 13 with biopsy-proven BKVN. We identified a 20-gene signature that differentiated intragraft injury from grafts with stable function (area under the curve (AUC), 0.991) and a distinct 40-gene signature distinguishing acute TCMR from BKVN (AUC = 1.00). Validation in separate 118 urine RNA samples obtained at time of surveillance or for-cause biopsies from Clinical Trials in Organ Transplantation (CTOT) -08 and CTOT-19 studies showed AUC of 0.77 for the 20-gene injury signature and AUC of 0.79 for the 40-gene signature. Our results highlight the utility of this flexible, non-invasive biomarker platform for rapid detection and differentiation of immune processes causing ongoing kidney graft injury.
Keslar et al. (Wed,) studied this question.