RT Journal Article
SR Electronic
T1 Cell-Free DNA and Active Rejection in Kidney Allografts
JF Journal of the American Society of Nephrology
JO J. Am. Soc. Nephrol.
FD American Society of Nephrology
SP 2221
OP 2232
DO 10.1681/ASN.2016091034
VO 28
IS 7
A1 Bloom, Roy D.
A1 Bromberg, Jonathan S.
A1 Poggio, Emilio D.
A1 Bunnapradist, Suphamai
A1 Langone, Anthony J.
A1 Sood, Puneet
A1 Matas, Arthur J.
A1 Mehta, Shikha
A1 Mannon, Roslyn B.
A1 Sharfuddin, Asif
A1 Fischbach, Bernard
A1 Narayanan, Mohanram
A1 Jordan, Stanley C.
A1 Cohen, David
A1 Weir, Matthew R.
A1 Hiller, David
A1 Prasad, Preethi
A1 Woodward, Robert N.
A1 Grskovic, Marica
A1 Sninsky, John J.
A1 Yee, James P.
A1 Brennan, Daniel C.
YR 2017
UL http://jasn.asnjournals.org/content/28/7/2221.abstract
AB Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell–mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell–mediated types ≥IB), 0.2% (T cell–mediated type IA), and 0.3% in controls (P=0.05 for T cell–mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell–mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.