Abstract: FR-PO803
Enhanced Histological Yield and Actionable Findings When Biopsy Is Guided by Donor-Derived Cell-Free DNA (dd-cfDNA)
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
- Weir, Matthew R., University of Maryland Baltimore, Baltimore, Maryland, United States
- Mandelbrot, Didier A., University of Wisconsin System, Madison, Wisconsin, United States
- Poggio, Emilio D., Cleveland Clinic, Cleveland, Ohio, United States
- Bromberg, Jonathan, University of Maryland Baltimore, Baltimore, Maryland, United States
- Mehta, Shikha, University of Alabama, Birmingham, Alabama, United States
- Tian, Wenlan, CareDx Inc, Brisbane, California, United States
- Agrawal, Nikhil, CareDx Inc, Brisbane, California, United States
- Cooper, Matthew, MedStar Georgetown University Hospital, Washington, District of Columbia, United States
Background
Implementation of molecular biomarkers in kidney transplantation has expanded the amount of information available to clinicians before deciding to pursue biopsy. We evaluated how use of donor-derived cell-free DNA testing (dd-cfDNA) impacts histologic biopsy yield.
Methods
1663 kidney transplant (KTx) recipients enrolled in the Kidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076) were followed with dd-cfDNA post-transplant; testing was obtained either as part of a surveillance strategy or for-cause; indications for biopsy and histologic diagnoses were captured.This analysis included only for-cause biopsies.
Results
65 biopsies (from 59 pts) driven by elevated dd-cfDNA levels were compared to 540 biopsies (392 pts) obtained for causes other than elevated dd-cfDNA. Patient age (55 vs 56 years), percent deceased donor (84.75% vs 78.83%), and biopsy timing post-transplant (123 vs 105.5 days) did not differ betweengroups. Among dd-cfDNA-guided biopsies, yield was enriched for rejection (48% vs 29%) and included fewer cases of ATI/ATN (12% vs 22%) compared to biopsies obtained for other causes (p<0.05) [Figure 1]. Among dd-cfDNA-guided biopsies with rejection (ABMR, TCMR, or Mixed), median dd-cfDNA was 1.46% (IQR: 1.15 - 2.87). Among biopsies not performed due to elevated dd-cfDNA but with paired results available (n = 267), median dd-cfDNA was0.24%. Within this group, patients with rejection had median dd-cfDNA of 0.82% and demonstrated an increase of 133% from the preceding result.
Conclusion
Dd-cfDNA surveillance enhances the histologic yield for actionable results in for-cause allograft biopsies. A low dd-cfDNA result can obviate the need for biopsy even in the presence of other clinical factors that are routinely used to guide the biopsy decision.
Funding
- Commercial Support – CareDx