Abstract: FR-PO804
Elevated Donor-Derived Cell-Free DNA (dd-cfDNA) in the Early Post-Transplant Period Is Associated With an Increased Incidence of Adverse Clinical Outcomes in Kidney Transplant Recipients
Session Information
- Transplantation: Clinical - Biomarkers
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Wojciechowski, David, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Brennan, Daniel C., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Paramesh, Anil S., Tulane University School of Medicine, New Orleans, Louisiana, United States
- Klein, Jeffrey A., University of Missouri Kansas City, Kansas City, Missouri, United States
- Agrawal, Nikhil, CareDx Inc, Brisbane, California, United States
- Fei, Mingwei, CareDx Inc, Brisbane, California, United States
- Qu, Kunbin, CareDx Inc, Brisbane, California, United States
- Sood, Puneet, UPMC, Pittsburgh, Pennsylvania, United States
Background
Early post-transplant elevations in dd-cfDNA, even in the absence of histologic rejection or other overt pathology, have been suggested to carry a risk of adverse outcomes among solid organ transplant recipients. We investigated this association among kidney transplant recipients enrolled in the Kidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076).
Methods
To assess the impact of early post-transplant dd-cfDNA elevations, we evaluated the incidence of a clinical composite that included biopsy-proven rejection (BPAR), detection of de novo donor specific antibodies (dnDSA) and return to dialysis in patients with and without median dd-cfDNA >1% over the first 100 days post-transplant. Patients with events before day 100 were excluded. Univariate and multivariate analyses were performed.
Results
51 of 1296 patients (3.9%) had a median dd-cfDNA ≥1.0% during the first 100 days post-transplant. In a univariate model, these patients had a significantly higher risk of experiencing both the composite outcome and each individual component during the first post-transplant year [Figure 1]. In a multivariate Cox proportional hazards model that included recipient age, delayed graft function, donor type (living vs deceased), and recipient sensitization,only 100-day median dd-cfDNA elevation ≥1.0% was a statistically significant predictor of the composite outcome, with a hazard ratio of 2.99 (95% CI: 1.59 -5.61, p < 0.005).
Conclusion
Our findings suggest that early post-transplant elevations in dd-cfDNA among kidney transplant recipients, even in the absence of clear immunologic or histologic correlates, identify a population of patients at risk for adverse clinical outcomes during the first post-transplant year. Molecular risk-stratification using dd-cfDNA may have implications for clinical surveillance and therapeutic management of these patients.
Funding
- Commercial Support – CareDx