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

Am J Transplant. 2024 Mar;24(3):436-447. doi: 10.1016/j.ajt.2023.09.021. Epub 2023 Dec 7.

Abstract

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 nonrandomized, 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 + serum creatinine at biopsy. Of the 151 kidney transplant recipients, 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 + 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 odds ratio 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.

Keywords: NGS blood signature; Tutivia; predicts early kidney transplant rejection.

Publication types

  • Observational Study

MeSH terms

  • Biomarkers / metabolism
  • Creatinine
  • Female
  • Graft Rejection / diagnosis
  • Graft Rejection / etiology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Kidney Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA

Substances

  • Creatinine
  • Biomarkers
  • RNA