The Role of Donor-derived Cell-free DNA to Detect Subclinical Acute Rejection in Kidney Allograft

S. Park¹, K. Guo², R. Heilman³, E. Poggio⁴, D. Taber⁵, C. Marsh⁶, S. Kurian⁷, S. Kleiboeker⁸, J. Weems⁹, J. Holman¹⁰, L. Zhao², R. Sinha⁸, S. Brietigam², C. Rebello², M. Abecassis¹¹, J. Friedewald¹

¹Transplant nephrology, Northwestern University, Chicago, IL, ²Feinberg School of Medicine, Northwestern University, Chicago, IL, ³Transplant nephrology, Mayo Clinic College of Medicine and Science, Phoenix, AZ, ⁴Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, OH, ⁵Division of Transplant Surgery, Medical University of South Carolina, Charleston, SC, ⁶Department of Medicine and Surgery, Scripps Clinic and Green Hospital, La Jolla, CA, ⁷Scripps Health, La Jolla, CA, ⁸Eurofins US Clinical Diagnostics, Lee's Summit, MO, ⁹Eurofins US Clinical Diagnostics, Lee’s Summit, MO, ¹⁰Transplant Genomics, Inc, Mansfield, MA, ¹¹University of Arizona College of Medicine, Northwestern University, Tucson, AZ

Meeting: 2021 American Transplant Congress

Abstract number: 222

Keywords: Genomic markers, Kidney transplantation, Outcome, Rejection

Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes

Session Information

Session Name: Biomarkers, Immune Assessment and Clinical Outcomes - III

Session Type: Rapid Fire Oral Abstract

Date: Monday, June 7, 2021

Session Time: 4:30pm-5:30pm

Presentation Time: 4:55pm-5:00pm

Location: Virtual

*Purpose: We hypothesized that donor-derived cell-free DNA (dd-cfDNA) could detect subclinical acute rejection (subAR).

*Methods: 429 blood samples paired with surveillance kidney biopsies from 208 patients with stable kidney function were analyzed. We used a commercially available dd-cfDNA assay, which provides a percentage of dd-cfDNA over total cfDNA. More than 0.7% of dd-cfDNA was reported as positive results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed. 95% confidence interval (CI) was calculated using bootstrapping with 10,000 iterations.

*Results: 429 samples consisted of 80.7% (n=346) with Transplant eXcellence (TX, no rejection) and 19.3% (n=83) with subAR. Among 83 subAR, 61.4% (n=51) were borderline, 32.5% (n=27) were antibody-mediated rejection (AMR) and 6% (n=5) Banff 1A rejection. The dd-cfDNA had sensitivity of 41% (95% CI, 0.28-0.54) and specificity of 85% (95% CI, 0.80-0.90). The PPV and NPV were 40% (95% CI, 0.27-0.52) and 86% (95% CI, 0.82-0.90), respectively (Table 1). The median dd-cfDNA in the subAR group (0.43%) was significantly higher than the TX group (0.31%, p<0.001) (Figure 1). The AMR group (2.29%) had significantly higher median than the acute cellular rejection (ACR) group (0.35%, p <0.001) or Tx group (0.31%, p<0.001) (Figure2). The dd-cfDNA was positive among 88.9% (n=24) of 27 AMR samples.

*Conclusions: The dd-cfDNA assay was able to detect 88.9% of subclinical AMR cases but was not as discriminatory for subclinical ACR.

To cite this abstract in AMA style:

Park S, Guo K, Heilman R, Poggio E, Taber D, Marsh C, Kurian S, Kleiboeker S, Weems J, Holman J, Zhao L, Sinha R, Brietigam S, Rebello C, Abecassis M, Friedewald J. The Role of Donor-derived Cell-free DNA to Detect Subclinical Acute Rejection in Kidney Allograft [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/the-role-of-donor-derived-cell-free-dna-to-detect-subclinical-acute-rejection-in-kidney-allograft/. Accessed May 11, 2025.

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