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Abstract: PO2398

Case Series: Systemic Infection Alters Background Cell-Free DNA and Influences Results of Donor-Derived Cell-Free DNA Transplant Rejection Assays

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Bunnapradist, Suphamai, University of California Los Angeles, Los Angeles, California, United States
  • Gauthier, Philippe M., Natera, Inc, San Carlos, California, United States
  • Tabriziani, Hossein, Natera, Inc, San Carlos, California, United States
  • Swenerton, Ryan, Natera, Inc, San Carlos, California, United States
  • Ahmed, Ebad, Natera, Inc, San Carlos, California, United States
  • McKanna, Trudy, Natera, Inc, San Carlos, California, United States
  • Billings, Paul Richard, Natera, Inc, San Carlos, California, United States
Introduction

Donor-derived cell-free DNA (dd-cfDNA), a biomarker for kidney transplant rejection (1,2) is reported as a percentage of background cfDNA. Various factors affect total cfDNA levels (3,4). We present 3 cases with elevated background cfDNA where dd-cfDNA was assayed for rejection assessment.

Case Description

1: A 78 year old man with end-stage renal disease (ESRD) underwent a kidney transplant. A biopsy at +6 months (m, all time points relative transplant date) due to an elevated creatinine level indicated an acute T cell-mediated rejection (TCMR). At +7m, the patient tested positive for BK viremia, and was treated. He was admitted for nephrectomy of his native kidney at +14m and tested positive for herpetic and cytomegalovirus (CMV) esophagitis and treated. A cfDNA analysis was negative for rejection with background cfDNA = 10,326 Arbitrary units (AU)/mL (~21X median cfDNA).) Banff chronic active cellular rejection was confirmed from a subsequent biopsy. 2: A 62 year old woman with ESRD who underwent a kidney transplant had a cfDNA assay +3 years, that was reported as a negative result. However, the background was elevated at 3,466 AU/mL (~7X median). She had a biopsy that showed BK virus-associated nephropathy and TCMR. 3: A 53 year old woman with ESRD had a kidney transplant from an ABO incompatible donor. A month later, she was diagnosed with dengue fever followed by acute allograft dysfunction. A biopsy at +6m showed active antibody-mediated rejection (ABMR). On a cfDNA assay at +7m indicated a negative result; however with an elevated background (6344 AU/mL, ~13X median). A biopsy showed resolution of ABMR and borderline acute cellular rejection.

Discussion

In all 3 cases, active viral infections may have caused elevated background cfDNA leading to false negative results in 2 cases. A cfDNA-based rejection assay only reporting a percentage of the total cfDNA may be inaccurate, particularly in patients with viral infections. Dd-cfDNA rejection assays should account for the variable background cfDNA when reporting results.

1. Bloom RD et al. J Am Soc Nephrol. 2017; 28(7):2221–32; 2. Sigdel TK et a. J Clin Med. 2019;8,19; 3. Sherwood K, Weimer ET. J Immunol Methods. 2018; 463:27–38; 4. Fleischhacker M, Schmidt B. Biochem Biophys Acta. 2007;1775:181–232