Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring
Alexandre Loupy, Anaïs Certain, Narin S. Tangprasertchai, Maud Racapé, Cindy Ursule‐Dufait, Kawthar Benbadi, Marc Raynaud, Evgeniya Vaskova, Corina Marchis, Sı́lvia Casas, Tim Hague, Oriol Bestard, Delphine Kervella, Carmen Lefaucheur, Thierry Viard, Olivier Aubert
Abstract
Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker for allograft injury detection. This study aimed to evaluate a new, decentralized dd-cfDNA testing kit against a centralized dd-cfDNA testing service broadly utilized in the United States. Kidney transplant recipients with decentralized and centralized dd-cfDNA measurements and concomitant kidney allograft biopsies were included in the study. 580 kidney allograft recipients from 3 referral centers were included for 603 total evaluations. Correlation between assays was evaluated using r-squared ( r 2 ) and Spearman’s rank correlation test, and associations with rejection using logistic regression analyses and discrimination using area under the curve. Mean dd-cfDNA levels from decentralized and centralized tests were 0.51% ± 0.81% and 0.43% ± 0.78%, respectively. The assays were highly correlated, with r 2 = 0.95 and Spearman’s rank correlation 0.88 ( p < 0.0001). Both tests showed significant association with allograft rejection ( p < 0.0001) and good and similar discriminations to predict rejection (AUC: 0.758 for the decentralized and AUC: 0.760 for the centralized dd-cfDNA; p = 0.8466). Consistency between the assays was also confirmed across clinical scenarios including post-transplant timepoint, allograft stability, and allograft rejection subcategories. This decentralized dd-cfDNA assessment demonstrates high accuracy and value to non-invasively monitor kidney recipients.