Pretransplant transcriptomic signature in peripheral blood predicts acute rejection and renal allograft loss

Early development of acute rejection after kidney transplantation is associated with diminished long-term graft survival. Predicting early acute rejection (EAR) at the time of transplant is important to risk-stratify patients and titrate immunosuppression accordingly. We performed whole-blood RNA sequencing at the time of transplant in 235 kidney transplant recipients enrolled in a prospective-cohort study [one discovery set (N=81), two validation sets (N=74 and N=80)] and evaluated the relationship with EAR and graft loss. We identified a blood based 23-gene set in recipients at the time of transplant that predicts the risk of EAR and is associated with late AR and allograft loss. This gene set is an important new tool to risk-stratify recipients before kidney transplantation and help guide immunosuppressive therapy accordingly. The transcriptomic profiles of discovery set (N=81) was used for identification of gene signatures associated with early acute rejection. The early acute rejection prediction with the gene signatures was validated on validation set V1 (N=74) and late acute rejection and graft loss was validated on combined datasets of V1 (N=74) and V2 (N=80).