TY - JOUR
T1 - Cell-free DNA for the detection of kidney allograft rejection
AU - Aubert, Olivier
AU - Ursule-Dufait, Cindy
AU - Brousse, Romain
AU - Gueguen, Juliette
AU - Racapé, Maud
AU - Raynaud, Marc
AU - Van Loon, Elisabet
AU - Pagliazzi, Angelica
AU - Huang, Edmund
AU - Jordan, Stanley C.
AU - Chavin, Kenneth D.
AU - Gupta, Gaurav
AU - Kumar, Dhiren
AU - Alhamad, Tarek
AU - Anand, Sanjiv
AU - Sanchez-Garcia, Jorge
AU - Abdalla, Basmah A.
AU - Hogan, Julien
AU - Garro, Rouba
AU - Dadhania, Darshana M.
AU - Jain, Pranjal
AU - Mandelbrot, Didier A.
AU - Naesens, Maarten
AU - Dandamudi, Raja
AU - Dharnidharka, Vikas R.
AU - Anglicheau, Dany
AU - Lefaucheur, Carmen
AU - Loupy, Alexandre
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/8
Y1 - 2024/8
N2 - Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P < 0.0001), T cell-mediated rejection (P < 0.0001) and mixed rejection (P < 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902–2.739; P < 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741–0.811) to 0.821 (95% CI 0.784–0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379.
AB - Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P < 0.0001), T cell-mediated rejection (P < 0.0001) and mixed rejection (P < 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902–2.739; P < 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741–0.811) to 0.821 (95% CI 0.784–0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379.
UR - http://www.scopus.com/inward/record.url?scp=85196781195&partnerID=8YFLogxK
U2 - 10.1038/s41591-024-03087-3
DO - 10.1038/s41591-024-03087-3
M3 - Article
C2 - 38824959
AN - SCOPUS:85196781195
SN - 1078-8956
VL - 30
SP - 2320
EP - 2327
JO - Nature medicine
JF - Nature medicine
IS - 8
ER -