Abstract: SA-PO383
Correlation Between Percentage Donor-Derived Cell-Free DNA (%dd-cfDNA) at Time of Allograft Biopsy and Rejection: Insights from the Multi-Center Pediatric Outcomes of Kidney Care in Renal Allografts (pOKRA) Study
Session Information
- Pediatric Nephrology - III
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Dandamudi, Raja, Washington University in St Louis, St Louis, Missouri, United States
- Walther, Leslie, Washington University in St Louis, St Louis, Missouri, United States
- Kelton, Megan, Seattle Children's Hospital, Seattle, Washington, United States
- Kamel, Margret, Emory University, Atlanta, Georgia, United States
- Smith, Jodi M., Seattle Children's Hospital, Seattle, Washington, United States
- Dharnidharka, Vikas R., Washington University in St Louis, St Louis, Missouri, United States
Background
The is prospective multi-center observational study to assess the accuracy of % dd-cfDNA as a biomarker for the detection of allograft rejection on simultaneous biopsy, in pediatric kidney transplant patients.
Methods
A total of 48 patients from 3 centers who underwent kidney biopsies within the first year post-transplantation were included in the study. We measured %dd-cfDNA levels using a targeted, multiplex PCR-based method analyzing single nucleotide polymorphisms. Patients were divided into two groups based on the presence or absence of allograft rejection, including subclinical rejection.
Results
We studied 77 samples of plasma %dd-cfDNA levels drawn on the same morning before kidney biopsies from 48 unique patients. Of 77 biopsies, 70 (91%) were surveillance biopsies, whereas 7 (9%) were diagnostic. We had 13 biopsy specimens from 12 patients with biopsy-proven acute rejection and 64 biopsy specimens from 44 patients without biopsy-proven acute rejection.
At rejection, the %dd-cfDNA median (IQR) level was significantly higher at 1.2% (IQR, 0.5%-2.0%) than the quiescent group (median, 0.26%; IQR, 0.18%-0.49%). The area under the curve was 0.82 (95% confidence interval 0.70 to 0.93).
Using a 1% cutoff, %dd-cfDNA had a specificity of 86 % (95% CI, 75% to 92%) and a sensitivity of 62 % (95% CI, 36% to 82%) in identifying active rejection. At the lower cutoff of 0.5%, %dd-cfDNA had a lower 75% specificity (95% CI, 63% to 84%) but higher 77% sensitivity (95% CI, 50% to 92 %) to discriminate biopsy-proven acute rejection from no rejection.
Conclusion
Prospective multicenter dd-cfDNA% levels timed to biopsy show a high accuracy with biopsy-proven acute rejection in children.
Funding
- Commercial Support – CareDx