Association between dd-cfDNA levels, de novo donor specific antibodies, and eGFR decline: An analysis of the DART cohort

Deirdre L Sawinski; Shikha Mehta; Tarek Alhamad; Jonathan S Bromberg; Bernard Fischbach; Thomas Aeschbacher; Srinka Ghosh; Grigoriy Shekhtman; Sham Dholakia; Daniel C Brennan; Emilio Poggio; Roy D Bloom; Stanley C Jordan

doi:10.1111/ctr.14402

Association between dd-cfDNA levels, de novo donor specific antibodies, and eGFR decline: An analysis of the DART cohort

Clin Transplant. 2021 Sep;35(9):e14402. doi: 10.1111/ctr.14402. Epub 2021 Jul 14.

Authors

Deirdre L Sawinski^{1

2}, Shikha Mehta³, Tarek Alhamad⁴, Jonathan S Bromberg⁵, Bernard Fischbach⁶, Thomas Aeschbacher⁷, Srinka Ghosh⁷, Grigoriy Shekhtman⁷, Sham Dholakia⁷, Daniel C Brennan⁸, Emilio Poggio⁹, Roy D Bloom^{1

2}, Stanley C Jordan^{10

11}

Affiliations

¹ Renal, Electrolyte, and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
² Penn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³ Section of Transplant Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴ Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
⁵ Department of Surgery and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁶ Baylor University Medical Center, Dallas, Texas, USA.
⁷ CareDx Inc., Brisbane, California, USA.
⁸ Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁹ Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁰ Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.
¹¹ Division of Nephrology, Cedars-Sinai Medical Center, Los Angeles, California, USA.

PMID: 34184326
DOI: 10.1111/ctr.14402

Abstract

Background: Donor-derived cell-free DNA (dd-cfDNA) is a marker of allograft injury in transplant recipients; however, the relationship between dd-cfDNA and other clinical parameters associated with adverse allograft outcomes is not well-characterized.

Methods: We performed a retrospective analysis of kidney transplant recipients from the DART cohort (ClinicalTrials.gov Identifier: NCT02424227) to evaluate the associations between eGFR decline, de novo donor-specific antibodies (dnDSA), and dd-cfDNA.

Results: Both elevated dd-cfDNA (≥1%) and dd-cfDNA variability (≥.34%) in the first post-transplant year were associated with decline in eGFR ≥25% in the second year (21.4% vs. 4.1%, P = .005; 25% vs. 3.6%, P = .002, respectively). Compared to samples from DSA negative patients, samples from patients with concurrent de novo HLA DSAs had higher dd-cfDNA levels (P < .0001).

Discussion: Abnormalities in dd-cfDNA levels are associated with clinical parameters commonly used as surrogate endpoints for adverse allograft outcomes, raising the possibility that molecular injury as characterized by dd-cfDNA could help identify patients at risk of these outcomes.

Keywords: alloantibody; biomarker; graft survival; kidney (allograft) function/dysfunction; monitoring: immune.

MeSH terms

Cell-Free Nucleic Acids*
Graft Rejection / etiology
HLA Antigens
Humans
Isoantibodies
Kidney Transplantation* / adverse effects
Retrospective Studies
Tissue Donors

Substances

Cell-Free Nucleic Acids
HLA Antigens
Isoantibodies

Associated data

ClinicalTrials.gov/NCT02424227