Use of Donor-Derived Cell-Free DNA Assay to Monitor Treatment Response to Allograft Rejection in Pediatric Renal Transplant Recipients

J. Steggerda¹, H. Phan Pizzo², J. Garrison², X. Zhang³, M. Haas⁴, I. Kim¹, S. Jordan¹, D. Puliyanda²

¹Comprehensive Transplant Center, Cedars Sinai Medical Center, West Hollywood, CA, ²Pediatric Nephrology, Cedars Sinai Medical Center, West Hollywood, CA, ³HLA Laboratory, Cedars-Sinai Med Center, West Hollywood, CA, ⁴Pathology, Cedars Sinai Medical Center, West Hollywood, CA

Meeting: 2020 American Transplant Congress

Abstract number: B-319

Keywords: Kidney, Pediatric, Rejection

Session Information

Session Name: Poster Session B: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

Presentation Time: 3:30pm-4:00pm

Location: Virtual

*Purpose: Acute rejection (AR) accounts for 13%-21% of graft failure in pediatrics (peds), with the number, severity, and response to treatment being a major determinant of long-term survival. With 10-year graft failure as high as 45.8%, early detection and optimizing treatment are essential. The detection of donor-derived cell-free DNA (dd-cfDNA, Allosure) has been shown to reliably identify allograft rejection in adult kidney transplant patients (pts). Here we evaluate the utility of dd-cfDNA for monitoring treatment response amongst peds renal transplant (tx) pts suffering rejection.

*Methods: 58 peds tx pts were enrolled between 4/2018 and 9/2019 and underwent initial testing with dd-cfDNA to monitor for AR. Allograft biopsy was performed for dd-cfDNA >1.0% and pts found to have AR on biopsy formed the study cohort. Treatment for AR consisted of IV pulse steroids with or without IVIg and rituximab. Dd-cfDNA, serum creatinine (SCr), histology, treatment and outcomes were evaluated.

*Results: 18/58(31%) patients had dd-cfDNA score >1.0%, of which 17 (94.4%) had rejection on histology. Median time from transplant to dd-cfDNA testing was 67 months (interquartile range, IQR 51-79). Median dd-cfDNA score was 2% (IQR 1.47-3.25). 10 pts (58.8%) had antibody ABMR, 2 pts(11.8%) had TCMR, and 5 pts (29.4%) had mixed ABMR and TCMR. SCr at time of biopsy was normal at 1.00 mg/dL (IQR 0.87-1.15 mg/dL), showed minimal change post treatment and did not correlate with dd-cfDNA (p=0.65). Following treatment, dd-cfDNA decreased for all types of rejection but remained >1.0% in both ABMR (median 1.8, IQR 0.89-3.13) and Mixed (1.4, 0.89-4.15) groups. Dd-cfDNA was lower for pts with TCMR (0.28, 0.27-0.28). Table 1 shows change in dd-cfDNA, DSA, AT1R testing between the 3 subgroups.

*Conclusions: dd-cfDNA represents a potential non-invasive method for early detection (despite stable creatinine) of rejection in the peds renal tx pts Pts with TCMR may be reliably followed by ddcf-DNA; however, it remains unclear whether persistently elevated dd-cfDNA in pts with ABMR is a reflection of ongoing subclinical rejection or an inherent limitation of the assay.

To cite this abstract in AMA style:

Steggerda J, Pizzo HPhan, Garrison J, Zhang X, Haas M, Kim I, Jordan S, Puliyanda D. Use of Donor-Derived Cell-Free DNA Assay to Monitor Treatment Response to Allograft Rejection in Pediatric Renal Transplant Recipients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/use-of-donor-derived-cell-free-dna-assay-to-monitor-treatment-response-to-allograft-rejection-in-pediatric-renal-transplant-recipients/. Accessed May 11, 2025.

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