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Abstract: FR-PO431

Beneficial Addition of Donor-Derived Cell-Free DNA Testing in Pediatric Kidney Transplantation

Session Information

  • Pediatric Nephrology - I
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology

Authors

  • Chandar, Jayanthi, University of Miami School of Medicine, Miami, Florida, United States
  • Defreitas, Marissa J., University of Miami School of Medicine, Miami, Florida, United States
  • Ponsirenas, Renata, CareDx Inc, San Francisco, California, United States
  • Burke, George William, University of Miami School of Medicine, Miami, Florida, United States

Group or Team Name

  • University of Miami
Background

Donor-derived cell- free DNA (dd-cfDNA) is a plasma biomarker to assess allograft injury in kidney transplant recipients (KTRs). Herein, we describe a single-center experience regarding indications for performing dd-cfDNA in pediatric KTRs and compare dd-cfDNA fractions in various clinical states.

Methods

Pediatric KTRs tested for dd-cfDNA for a clinical indication were reviewed in a cross-sectional, observational study. Median values were compared between each indicated category. Sensitivity and specificity of dd-cfDNA to predict biopsy-proven graft injury was determined.by ROC curve analysis.

Results

dd-cfDNA was done in 77 children with a mean age of 11.6 ± 5.9 years. Mean time from transplant to testing was 3.5 ± 3.2 years. Indications for testing included presence of alloantibodies (N=12), clinical suspicion of rejection (N=7), BK nephropathy (N=1), reduced immunosuppression because of leukopenia, viral replication or recurrent bacterial infections (N=30), fluctuating serum creatinine (N=7), or increased serum creatinine with normal growth (N=6), increased post-transplant baseline creatinine for age (N=10) and suspected non-adherence with low tacrolimus levels (N=4). There was a significant difference in dd-cfDNA between children who had biopsy-proven acute rejection (BPAR), BK virus nephropathy (BKVN) and those who had alloantibodies (median 1.35 (95% CI 0.6,2.4) versus those who did not [median 0.3 (95%CI 0.25, 0.43); p =0.0012]. Children who were on lower doses of immunosuppression because of leukopenia, viral or bacterial infections had low dd-cfDNA [median score: 0.32 (95%CI 0.25, 0.45); Figure 1]. ROC curve analysis revealed AUC of 98%, specificity 92.5% and sensitivity of 70% for dd-cfDNA to predict graft injury in the presence of alloantibodies.

Conclusion

dd-cfDNA is a clinically useful adjuvant tool to determine allograft injury in pediatric KTRs which helps distinguish immune activation from immune quiescence. It has the potential to guide and serially monitor immunosuppression dosing.

Figure 1