Deirdre L Sawinski1,2, Shikha Mehta3, Tarek Alhamad4, Jonathan S Bromberg5, Bernard Fischbach6, Thomas Aeschbacher7, Srinka Ghosh7, Grigoriy Shekhtman7, Sham Dholakia7, Daniel C Brennan8, Emilio Poggio9, Roy D Bloom1,2, Stanley C Jordan10,11. 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.
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.
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.
Authors: Megan Kamath; Grigoriy Shekhtman; Tristan Grogan; Michelle J Hickey; Irina Silacheva; Karishma S Shah; Kishan S Shah; Adrian Hairapetian; Diego Gonzalez; Giovanny Godoy; Elaine F Reed; David Elashoff; Galyna Bondar; Mario C Deng Journal: Front Immunol Date: 2022-02-18 Impact factor: 8.786