Delta Changes in Donor-Derived Cell-Free DNA (dd-cfDNA) Complement the Donor Fraction in Kidney Transplant Surveillance
1Centura Health, Denver, CO, 2George Washington University, Washington, DC, 3Virginia Commonwealth University, Richmond, VA, 4Medical University of South Carolina, Charleston, SC, 5Baylor Scott and White, Austin, TX, 6CareDx, Brisbane, CA, 7Intermountain Healthcare, Murray, UT
Meeting: 2022 American Transplant Congress
Abstract number: 1540
Keywords: Kidney transplantation, Monitoring, Multicenter studies, Rejection
Topic: Basic Science » Basic Clinical Science » 17 - Biomarkers: Clinical Outcomes
Session Information
Session Name: Biomarkers: Clinical Outcomes
Session Type: Poster Abstract
Date: Tuesday, June 7, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Delta changes in dd-cfDNA levels over time may identify patients with evolving alloimmune injury, providing complementary information to the donor fraction. We explored the dd-cfDNA trajectories preceding biopsy-proven rejection (BPAR) events among kidney transplant recipients enrolled in the Kidney 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 identified patients 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 lowest of two preceding results as the patient-specific 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, including one within 30 days of the index biopsy. 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 median dd-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.
*Conclusions: Longitudinal surveillance with dd-cfDNA allows the integration of delta changes and trajectories over time, allowing earlier identification of evolving 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.
To cite this abstract in AMA style:
Wiseman A, Jagadeesan M, Gupta G, Rao V, Narayanan M, Agrawal N, Shekhtman G, Fu Y, Pinney K, Anand S. Delta Changes in Donor-Derived Cell-Free DNA (dd-cfDNA) Complement the Donor Fraction in Kidney Transplant Surveillance [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/delta-changes-in-donor-derived-cell-free-dna-dd-cfdna-complement-the-donor-fraction-in-kidney-transplant-surveillance/. Accessed May 6, 2025.« Back to 2022 American Transplant Congress