Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study.
Axelrod, David A
Weir, Matthew R
Wolf-Doty, Theresa K
De Golovine, Aleskandra
Bromberg, Jonathan S
MetadataShow full item record
AbstractThe use of routine monitoring of donor-derived cell-free DNA (dd-cfDNA) after kidney transplant may allow clinicians to identify subclinical allograft injury and intervene prior to development of clinically evident graft injury. To evaluate this, data from 1092 kidney transplant recipients monitored for dd-cfDNA over a three-year period was analyzed to assess the association of dd-cfDNA with histologic evidence of allograft rejection. Elevation of dd-cfDNA (0.5% or more) was significantly correlated with clinical and subclinical allograft rejection. dd-cfDNA values of 0.5% or more were associated with a nearly three-fold increase in risk development of de novo donor-specific antibodies (hazard ratio 2.71) and were determined to be elevated a median of 91 days (interquartile range of 30-125 days) ahead of donor specific antibody identification. Persistently elevated dd-cfDNA (more than one result above the 0.5% threshold) predicted over a 25% decline in the estimated glomerular filtration rate over three years (hazard ratio 1.97). Therefore, routine monitoring of dd-cfDNA allowed early identification of clinically important graft injury. Biomarker monitoring complemented histology and traditional laboratory surveillance strategies as a prognostic marker and risk-stratification tool post-transplant. Thus, persistently low dd-cfDNA levels may accurately identify allograft quiescence or absence of injury, paving the way for personalization of immunosuppression trials.
Rights/TermsCopyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
donor-derived cell-free DNA
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/18111
- An Assessment of the Value of Donor-derived Cell-free DNA Surveillance in Patients With Preserved Kidney Allograft Function.
- Authors: Huang E, Haas M, Gillespie M, Sethi S, Peng A, Najjar R, Vo A, Jordan SC
- Issue date: 2023 Jan 1
- Use of a donor-derived cell-free DNA assay to monitor treatment response in pediatric renal transplant recipients with allograft rejection.
- Authors: Steggerda JA, Pizzo H, Garrison J, Zhang X, Haas M, Kim IK, Jordan SC, Puliyanda DP
- Issue date: 2022 Jun
- High levels of dd-cfDNA identify patients with TCMR 1A and borderline allograft rejection at elevated risk of graft injury.
- Authors: Stites E, Kumar D, Olaitan O, John Swanson S, Leca N, Weir M, Bromberg J, Melancon J, Agha I, Fattah H, Alhamad T, Qazi Y, Wiseman A, Gupta G
- Issue date: 2020 Sep
- Combining donor-derived cell-free DNA and donor specific antibody testing as non-invasive biomarkers for rejection in kidney transplantation.
- Authors: Obrișcă B, Butiu M, Sibulesky L, Bakthavatsalam R, Smith KD, Gimferrer I, Warner P, Ismail G, Leca N
- Issue date: 2022 Sep 5
- Absolute quantification of donor-derived cell-free DNA as a marker of rejection and graft injury in kidney transplantation: Results from a prospective observational study.
- Authors: Oellerich M, Shipkova M, Asendorf T, Walson PD, Schauerte V, Mettenmeyer N, Kabakchiev M, Hasche G, Gröne HJ, Friede T, Wieland E, Schwenger V, Schütz E, Beck J
- Issue date: 2019 Nov