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

Oriol Bestard, Joshua Augustine, Alvin Wee, Emilio Poggio, Roslyn B. Mannon, Mohammed Javeed Ansari, Chandra Bhati, Daniel Maluf, Scott Benken, Nicolae Leca, Gaetano La Manna, Milagros Samaniego-Picota, Saed Shawar, Beatrice P. Concepcion, Lionel Rostaing, Federico Alberici, Phillip O'Connell, Anthony Chang, Fadi Salem, Michael W. KattanLorenzo Gallon, Michael J. Donovan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)436-447
Number of pages12
JournalAmerican Journal of Transplantation
Volume24
Issue number3
DOIs
StatePublished - Mar 2024

Keywords

  • NGS blood signature
  • Tutivia
  • predicts early kidney transplant rejection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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