Elevated Donor Derived Cell Free DNA (dd-cfDNA) Levels in the Presence of Donor Specific Antibodies (DSA) Are a Strong Predictor of Antibody Mediated Rejection (ABMR) in Pediatric Renal Transplant Recipients
1Pediatric Nephrology, Cedars-Sinai Med Ctr, Los Angeles, CA, 2Pediatric Nephrology, UTHealth, Houston, TX
Meeting: 2019 American Transplant Congress
Abstract number: 347
Keywords: Kidney transplantation, Monitoring, Pediatric, Rejection
Session Information
Session Name: Concurrent Session: Kidney: Pediatrics II
Session Type: Concurrent Session
Date: Monday, June 3, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 5:06pm-5:18pm
Location: Room 304
*Purpose: A renal biopsy, the gold standard for the diagnosis of antibody mediated rejection (ABMR) in transplant recipients, is invasive and may be associated with adverse events. Circulating donor-derived cell free DNA (dd-cfDNA) (Allosure; CareDx) is a recently developed non-invasive marker of cell injury, known to have a strong predictive value for the diagnosis of both acute and chronic ABMR in adult renal transplantation. However, it has not been studied in pediatric renal transplant recipients (pts). Here we investigated the presence of dd-cfDNA (expressed as %) in plasma samples of 24 pts (<21 years) and correlated them with histology, presence of donor-specific antibodies (DSA) and/or angiotensin II type 1 receptor antibodies (AT1R).
*Methods: Between April and November 2018, 24 patients who presented with either increase in creatinine and/or +DSA and/or +AT1R and/or new onset proteinuria were identified as having high risk of rejection. dd-cfDNA testing was done with kits provided for compassionate use by CareDx. 13/24 patients underwent a renal biopsy. Clinical course was followed.
*Results: 13/24 patients underwent a renal biopsy: 10 had +DSA (with 3 having +AT1R) and 2 had isolated +AT1R. 11/13 patients showed ABMR on histology; 1 patient with no DSA and isolated AT1R showed Calcineurin inhibitor toxicity and one patient with no DSA showed T-cell mediated rejection. Median dd-cfDNA in pts with positive DSA (n=15) was 1.95% (<0.19-10%); median dd-cfDNA in pts with negative DSA (n=9) was 0.33% (<0.19-2.3%), p=0.01. Median dd-cfDNA in pts with ABMR (n=11) was 1.95% (0.34-10%). Median dd-cfDNA in patients with isolated +AT1R (n=4) was 0.31% (0.19-0.34%).
| Median DD-cfDNA | Range | P value | |
| +DSA (n=15) | 1.95% | <0.19-10% | |
| -DSA (n=9) | 0.33% | <0.19-2.3 | 0.01 |
| ABMR (n=11) | 1.95% | 0.34-10% | |
| +AT1R (n=4) | 0.31% | 0.19-0.34 |
*Conclusions: 1) +DSA and high dd-cfDNA is a predictor of ABMR. 2) Patients with renal dysfunction with dd-cfDNA levels <1% and no DSA did not show ABMR. 3) Patients with isolated +AT1R show low levels of dd-cfDNA and no evidence of ABMR on biopsy. Serial dd-cfDNA may serve as a dynamic biomarker in patients undergoing treatments for ABMR. Larger studies are needed to confirm the utility of dd-cfDNA in the non-invasive diagnosis of rejection in pts. The combined use of dd-cfDNA and DSA testing may improve our ability to diagnose ABMR which would enable more frequent and safer assessment of allograft rejection/injury.
To cite this abstract in AMA style:
Puliyanda D, Swinford RD, Pizzo H, Garrison J, Kim I, Golovine AMDe, Jordan S. Elevated Donor Derived Cell Free DNA (dd-cfDNA) Levels in the Presence of Donor Specific Antibodies (DSA) Are a Strong Predictor of Antibody Mediated Rejection (ABMR) in Pediatric Renal Transplant Recipients [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/elevated-donor-derived-cell-free-dna-dd-cfdna-levels-in-the-presence-of-donor-specific-antibodies-dsa-are-a-strong-predictor-of-antibody-mediated-rejection-abmr-in-pediatric-renal-transplant-rec/. Accessed November 22, 2024.« Back to 2019 American Transplant Congress