Prospective observational study to validate a next-generation sequencing blood RNA signature to predict early kidney transplant rejection

The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post-kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a non-randomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia thorn serum creatinine at biopsy. Of the 151 kidney transplant re-cipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia thorn creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100)generated a high- and low-risk category for AR with a negative predictive value of 0.79(95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odd sratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.