344.2: Delta Changes in Donor-Derived Cell-Free DNA (dd-cfDNA) Complement the Donor Fraction in Kidney Transplant Surveillance

Abstract

Introduction: Delta changes in dd-cfDNA levels over time may identify patients with evolving alloimmune injury, providing complementary information to thedonor fraction. We explored the dd-cfDNA trajectories preceding biopsy-proven rejection (BPAR) events among kidney transplant recipients enrolled in theKidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076) and undergoing longitudinal surveillance with dd-cfDNA. Methods: In the primary analysis, we compared the change in dd-cfDNA from baseline to the time of BPAR (for-cause or surveillance biopsies). We identifiedpatients with first-time rejection events and at least 3 prior dd-cfDNA results; the index result was obtained ≤30 days before BPAR; we then selected the lowestof two preceding results as the patient-specific baseline and compared this with the index result. We then analyzed patients with rejection (first or subsequent, atleast 90 days apart) and ≥2 dd-cfDNA results, including one within 30 days of the index biopsy. The reference change value (RCV) was calculated using areference 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-cfDNAvalues obtained 69 days (IQR: 45 - 108) apart preceded biopsy-proven rejection events (Table 1B). The calculated RCV for the stable reference population withinKOAR was 56.3%. 39 of these 51 events (76%) demonstrated increases greater than this RCV. Conclusions: Longitudinal surveillance with dd-cfDNA allows the integration of delta changes and trajectories over time, allowing earlier identification ofevolving allograft injury. Significant changes from an established baseline and between sequential values ahead of biopsy-proven rejection highlight how longitudinal surveillance may improve diagnostic performance.