TY - JOUR
T1 - Prospective observational study to validate a next-generation sequencing blood RNA signature to predict early kidney transplant rejection
AU - Bestard, Oriol
AU - Augustine, Joshua
AU - Wee, Alvin
AU - Poggio, Emilio
AU - Mannon, Roslyn B
AU - Ansari, Mohammed Javeed
AU - Bhati, Chandra
AU - Maluf, Daniel
AU - Benken, Scott
AU - Leca, Nicolae
AU - La Manna, Gaetano
AU - Samaniego-Picota, Milagros
AU - Shawar, Saed
AU - Concepcion, Beatrice P
AU - Rostaing, Lionel
AU - Alberici, Federico
AU - O'Connell, Phillip
AU - Chang, Anthony
AU - Salem, Fadi
AU - Kattan, Michael W
AU - Gallon, Lorenzo
AU - Donovan, Michael J
N1 - Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2023/11/29
Y1 - 2023/11/29
N2 - 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.
AB - 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.
U2 - 10.1016/j.ajt.2023.09.021
DO - 10.1016/j.ajt.2023.09.021
M3 - Article
C2 - 38152017
SN - 1600-6135
JO - American Journal of Transplantation
JF - American Journal of Transplantation
ER -