Abstract: FR-PO781
Delta Changes in Donor-Derived Cell-Free DNA (dd-cfDNA) Complement the Donor Fraction in Kidney Transplant Surveillance
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
- Wiseman, Alexander C., Centura Health, Englewood, Colorado, United States
- Narayanan, Mohanram, Baylor Scott & White Health, Dallas, Texas, United States
- Agrawal, Nikhil, CareDx Inc, Brisbane, California, United States
- Shekhtman, Grigoriy, CareDx Inc, Brisbane, California, United States
- Fu, Yi, CareDx Inc, Brisbane, California, United States
- Pinney, Kevin, CareDx Inc, Brisbane, California, United States
- Gupta, Gaurav, Virginia Commonwealth University, Richmond, Virginia, United States
Background
We explored dd-cfDNA trajectories preceding biopsy-proven rejection (BPAR) events among kidney transplant recipients in the Kidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076) and undergoing surveillance with dd-cfDNA.
Methods
We compared the change in dd-cfDNA from baseline to the time of BPAR (for-cause or surveillance biopsies). We identified patients with first-time rejection events and at least 3 prior dd-cfDNA results; selected the lowest of two preceding results as the baseline and compared this with the index result. We then analyzed patients with rejection (first or subsequent, at least 90 days apart) and ≥2 dd-cfDNA results. The reference change value (RCV) was calculated using a reference population of patients with stable allograft function, at least 3 dd-cfDNA measurements, and no significant clinical events.
Results
A total of 28 patients with BPAR met criteria for the primary analysis; among these, median baseline dd-cfDNA was 0.22% (IQR: 0.19 - 0.35) and mediandd-cfDNA at the time of rejection was 1.35% (IQR: 0.75 - 2.75), representing a 491% (IQR: 177 - 1133) increase between these results, obtained 71.5 (IQR: 46 -113) days apart [Table 1a]. 51 events met criteria for the second analysis where a median increase of 253% (IQR: 72 - 821%) between sequential dd-cfDNA values obtained 69 days (IQR: 45 - 108) apart preceded biopsy-proven rejection events [Table 1b]. The calculated RCV for the stable reference population within KOAR was 56.3%. 39 of these 51 events (76%) demonstrated increases greater than this RCV.
Conclusion
Longitudinal surveillance with dd-cfDNA allows the integration of delta changes and trajectories over time, allowing earlier identification of evolving allograft injury.
Funding
- Commercial Support – CareDx