Performance and Advancement of the Kidney Solid Organ Response Test

BACKGROUND. The kidney solid organ response test (kSORT) has been investigated for the prediction of acute rejection in kidney transplant recipients with conflicting results. We aimed to investigate if the kSORT assay score is associated with rejection or immune quiescence. METHODS. The blinded association between rejection and kSORT > 9 were investigated. Optimization of kSORT prediction was evaluated after unblinding to determine the optimal prediction cutoff value of kSORT score. Additionally, the predictive capability of the kSORT gene set was assessed using blinded normalized gene expression data from microarray (Affymetrix) and qPCR assays. RESULTS. Of the 95 blood samples analyzed, 18 patients had blood samples before transplant, 77 patients after transplant and 71 had clinically indicated biopsies of which 15 biopsies showed acute rejection and 16 showed chronic active antibody-mediated rejection. When 31 patients with rejection were compared to the remaining 64 patients, positive predictive value (PPV) was 54.29% and negative predictive value (NPV) was 75% when stratified using a kSORT score > 9, and PPV was 57.89% and NPV was 78.95% when stratified using a kSORT score > 5. Using the kSORT assay for detection of rejection showed an area under the curve value of 0.71. Microarray data improved prediction accuracy with PPV of 53% and NPV of 84% compared to qPCR results (PPV and NPV were 36% and 66%), respectively. CONCLUSIONS. The kSORT assay has the potential to be used as a predictive tool for active rejection and/or immune quiescence, but additional studies will be useful in improving and refining the kSORT assay, in particular the prediction algorithm.