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

Autor: Sawinski DL; Renal, Electrolyte, and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Penn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA., Mehta S; Section of Transplant Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA., Alhamad T; Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Bromberg JS; Department of Surgery and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA., Fischbach B; Baylor University Medical Center, Dallas, Texas, USA., Aeschbacher T; CareDx Inc., Brisbane, California, USA., Ghosh S; CareDx Inc., Brisbane, California, USA., Shekhtman G; CareDx Inc., Brisbane, California, USA., Dholakia S; CareDx Inc., Brisbane, California, USA., Brennan DC; Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Poggio E; Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, Ohio, USA., Bloom RD; Renal, Electrolyte, and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Penn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA., Jordan SC; Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.; Division of Nephrology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Jazyk: angličtina
Zdroj: Clinical transplantation [Clin Transplant] 2021 Sep; Vol. 35 (9), pp. e14402. Date of Electronic Publication: 2021 Jul 14.
DOI: 10.1111/ctr.14402
Abstrakt: 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.
(© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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