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. 2024 Dec 17:37:13919.
doi: 10.3389/ti.2024.13919. eCollection 2024.

Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring

Alexandre Loupy  1   2 , Anaïs Certain  1 , Narin S Tangprasertchai  3 , Maud Racapé  1 , Cindy Ursule-Dufait  1 , Kawthar Benbadi  1 , Marc Raynaud  1 , Evgeniya Vaskova  3 , Corina Marchis  3 , Sílvia Casas  3 , Tim Hague  3 , Oriol Bestard  4 , Delphine Kervella  4 , Carmen Lefaucheur  1   5 , Thierry Viard  3 , Olivier Aubert  1   2
Affiliations

Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring

Alexandre Loupy et al. Transpl Int. .

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.

Keywords: AlloSeq; allograft rejection; dd-cfDNA; liquid biopsy; non-invasive diagnosis.

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Conflict of interest statement

CareDx participated in dd-cfDNA testing by providing reagents for decentralized testing, blinded to clinical information, and reviewed the manuscript and data analysis. Authors NT, EV, CM, SC, TH, and TV were employed by the company CareDx. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Distribution of decentralized (A) and centralized (B) dd-cfDNA results among the cohort. The y-axis corresponds to the number of samples (logarithmic scale).
FIGURE 2
FIGURE 2
Violin plot distribution of decentralized (A) and centralized (B) dd-cfDNA results. Each point represents a single sample. The black horizontal lines represent the central tendencies. The beans represent the smoothed densities, and the rectangles represent the inference intervals with confidence intervals (decentralized dd-cfDNA in blue, centralized dd-cfDNA in red).
FIGURE 3
FIGURE 3
Correlation of decentralized and centralized dd-cfDNA results, with r 2 = 0.95. Each point represents a single sample. The y-axis corresponds to the decentralized dd-cfDNA and the x-axis corresponds to the centralized dd-cfDNA using continuous scale (A) and logarithmic scale (B).
FIGURE 4
FIGURE 4
Association of decentralized and centralized dd-cfDNA with rejection. This figure represents the mean level of decentralized and centralized dd-cfDNA according to the presence or absence of rejection. Each dot corresponds to an individual dd-cfDNA value. Data are presented as mean values ± SEM.
FIGURE 5
FIGURE 5
ROC curves of the centralized and decentralized dd-cfDNA to detect rejection. The red ROC curve corresponds to centralized dd-cfDNA alone and the blue curve to decentralized dd-cfDNA alone for the detection of rejection. There was no difference between the two tests (p = 0.8466).
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