TY - JOUR
T1 - High levels of dd-cfDNA identify patients with TCMR 1A and borderline allograft rejection at elevated risk of graft injury
AU - Stites, Erik
AU - Kumar, Dhiren
AU - Olaitan, Oyedolamu
AU - John Swanson, Sidney
AU - Leca, Nicolae
AU - Weir, Matthew
AU - Bromberg, Jonathan
AU - Melancon, Joseph
AU - Agha, Irfan
AU - Fattah, Hasan
AU - Alhamad, Tarek
AU - Qazi, Yasir
AU - Wiseman, Alexander
AU - Gupta, Gaurav
N1 - Publisher Copyright:
© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2020/9/1
Y1 - 2020/9/1
N2 - The clinical importance of subclinical, early T cell–mediated rejection (Banff TCMR 1A and borderline lesions) remains unclear, due, in part to the fact that histologic lesions used to characterize early TCMR can be nonspecific. Donor-derived cell-free DNA (dd-cfDNA) is an important molecular marker of active graft injury. Over a study period from June 2017 to May 2019, we assessed clinical outcomes in 79 patients diagnosed with TCMR 1A/borderline rejection across 11 US centers with a simultaneous measurement of dd-cfDNA. Forty-two patients had elevated dd-cfDNA (≥0.5%) and 37 patients had low levels (<0.5%). Elevated levels of dd-cfDNA predicted adverse clinical outcomes: among patients with elevated cfDNA, estimated glomerular filtration rate declined by 8.5% (interquartile rate [IQR] −16.22% to −1.39%) (−3.50 mL/min/1.73 m2 IQR −8.00 to −1.00) vs 0% (−4.92%, 4.76%) in low dd-cfDNA patients (P =.004), de novo donor-specific antibody formation was seen in 40% (17/42) vs 2.7% (P <.0001), and future or persistent rejection occurred in 9 of 42 patients (21.4%) vs 0% (P =.003). The use of dd-cfDNA may complement the Banff classification and to risk stratify patients with borderline/TCMR 1A identified on biopsy.
AB - The clinical importance of subclinical, early T cell–mediated rejection (Banff TCMR 1A and borderline lesions) remains unclear, due, in part to the fact that histologic lesions used to characterize early TCMR can be nonspecific. Donor-derived cell-free DNA (dd-cfDNA) is an important molecular marker of active graft injury. Over a study period from June 2017 to May 2019, we assessed clinical outcomes in 79 patients diagnosed with TCMR 1A/borderline rejection across 11 US centers with a simultaneous measurement of dd-cfDNA. Forty-two patients had elevated dd-cfDNA (≥0.5%) and 37 patients had low levels (<0.5%). Elevated levels of dd-cfDNA predicted adverse clinical outcomes: among patients with elevated cfDNA, estimated glomerular filtration rate declined by 8.5% (interquartile rate [IQR] −16.22% to −1.39%) (−3.50 mL/min/1.73 m2 IQR −8.00 to −1.00) vs 0% (−4.92%, 4.76%) in low dd-cfDNA patients (P =.004), de novo donor-specific antibody formation was seen in 40% (17/42) vs 2.7% (P <.0001), and future or persistent rejection occurred in 9 of 42 patients (21.4%) vs 0% (P =.003). The use of dd-cfDNA may complement the Banff classification and to risk stratify patients with borderline/TCMR 1A identified on biopsy.
KW - biomarker
KW - cellular transplantation (non-islet)
KW - clinical research/practice
KW - kidney (allograft) function/dysfunction
KW - kidney failure/injury
KW - monitoring: immune
KW - rejection: T cell mediated (TCMR)
UR - http://www.scopus.com/inward/record.url?scp=85081281914&partnerID=8YFLogxK
U2 - 10.1111/ajt.15822
DO - 10.1111/ajt.15822
M3 - Article
C2 - 32056331
AN - SCOPUS:85081281914
SN - 1600-6135
VL - 20
SP - 2491
EP - 2498
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 9
ER -