TY - JOUR
T1 - Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study
AU - Bu, Lihong
AU - Gupta, Gaurav
AU - Pai, Akshta
AU - Anand, Sanjiv
AU - Stites, Erik
AU - Moinuddin, Irfan
AU - Bowers, Victor
AU - Jain, Pranjal
AU - Axelrod, David A.
AU - Weir, Matthew R.
AU - Wolf-Doty, Theresa K.
AU - Zeng, Jijiao
AU - Tian, Wenlan
AU - Qu, Kunbin
AU - Woodward, Robert
AU - Dholakia, Sham
AU - De Golovine, Aleskandra
AU - Bromberg, Jonathan S.
AU - Murad, Haris
AU - Alhamad, Tarek
N1 - Funding Information:
GG serves on the scientific advisory board of CareDx and has received honoraria/grant support from Alexion, CareDx, Mallinckrodt, Natera, Veloxis, Gilead, National Institutes of Health/National Institutes of Diabetes and Digestive and Kidney Diseases, and the Mendez Foundation. AP has received an educational research grant from CareDx. SA has received speaker honorarium from CareDx. ES has received speaker and advisory board honorarium from CareDx. PJ has received speaker and advisory board honorarium from CareDx and owns common stock in CareDx. DAA is a member of the CareDx National Scientific Advisory Board and serves as a consultant for CareDx and Talaria. MW has received speaker, consulting, and advisory board honorarium from CareDx. TKW-D, JZ, WT, KQ, RW, and SD are employees of CareDx. JSB has received research funding from CareDx, Natera, and the University of Alberta. TA has received speaker and advisory board honorarium from CareDx. All the other authors declared no competing interests.
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2022/4
Y1 - 2022/4
N2 - The 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.
AB - The 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.
KW - allograft injury
KW - allograft quiescence
KW - biomarker
KW - donor-derived cell-free DNA
KW - kidney transplant
KW - rejection surveillance
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U2 - 10.1016/j.kint.2021.11.034
DO - 10.1016/j.kint.2021.11.034
M3 - Article
C2 - 34953773
AN - SCOPUS:85125312675
VL - 101
SP - 793
EP - 803
JO - Kidney international
JF - Kidney international
SN - 0085-2538
IS - 4
ER -