Kidney Week

Abstract: FR-PO765

Donor-Derived Cell-Free DNA (dd-cfDNA) for Assessment of Response After Treatment of Allograft Rejection

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

• Gohh, Reginald Y., Rhode Island Hospital, Providence, Rhode Island, United States

Reginald Y. Gohh,

• Akalin, Enver, Montefiore Medical Center, Bronx, New York, United States

Enver Akalin,

• Klein, Jeffrey A., University of Kansas Medical Center Department of Internal Medicine, Kansas City, Kansas, United States

Jeffrey A. Klein,

• Agrawal, Nikhil, CareDx Inc, Brisbane, California, United States

Nikhil Agrawal,

• Shekhtman, Grigoriy, CareDx Inc, Brisbane, California, United States

Grigoriy Shekhtman,

• Fu, Yi, CareDx Inc, Brisbane, California, United States

Yi Fu,

• Weir, Matthew R., University of Maryland Baltimore, Baltimore, Maryland, United States

Matthew R. Weir,

Background

Surveillance of dd-cfDNA after therapy for rejection represents a promising strategy for monitoring post-treatment response. We assessed post-rejection kinetics of dd-cfDNA among kidney transplant recipients in the Kidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076).

Methods

We identified patients with biopsy-proven allograft rejection (BPAR), defined as ABMR, TCMR, or Mixed (Banff 2019), biopsy-paired dd-cfDNAmeasurements (within ≤30d of biopsy), and follow-up results 60-150 days after BPAR. When available, treatment and follow-up histology data was also analyzed.

Results

48 episodes of BPAR (24 TCMR, 19 ABMR, 5 Mixed) and paired dd-cfDNA results were identified in 42 patients. Overall, a significantreduction was seen between the median index (1.36%, IQR: 0.29-2.25) and follow-up dd-cfDNA results (0.35%, IQR: 0.13-0.95; p < 0.01) [Figure 1a]. For patients with concurrent eGFR measurements, no statistically significant improvement was seen. These patterns held when analysis was limited to TCMR and ABMR/Mixed rejections [Figure 1b, 1c]. 7 patients (2 ABMR, 4 TCMR, and 1 Mixed; median index dd-cfDNA 1.15%, IQR: 0.31-2.46) had repeat biopsies within 30days of their follow-up testing; 1 patient with acute ABMR had chronic active ABMR on repeat biopsy, with a dd-cfDNA of 1.86%, while the remainder had eitherno rejection or borderline findings (median dd-cfDNA 0.74%, IQR: 0.30-2.59).

Conclusion

Our findings highlight that reduction in dd-cfDNA is commonly seen following BPAR, suggesting that most patients experience a “molecularresponse” to therapy. Studies are needed to better understand the prognostic significance of a molecular response and how persistent elevations in dd-cfDNA after treatment should guide subsequent management.

Funding

• Commercial Support – CareDx