Cell-Free DNA and active rejection in kidney allografts

for the Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators

Research output: Contribution to journalArticle

Abstract

Histologicanalysis of the allograftbiopsy specimen is the standardmethodused todifferentiate rejection fromother injury in kidney transplants.Donor-derived cell-freeDNA(dd-cfDNA) is a noninvasive test of allograft injury thatmay enablemore 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 negativepredictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61%and84%, respectively. TheAUCfor discriminatingABMRfromsampleswithoutABMR was 0.87 (95%CI, 0.75 to 0.97). Positive and negative predictive values forABMRat 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, ddcfDNA 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.

Original languageEnglish (US)
Pages (from-to)2221-2232
Number of pages12
JournalJournal of the American Society of Nephrology
Volume28
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

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Allografts
Kidney
DNA
T-Lymphocytes
Wounds and Injuries
Biopsy
Antibodies
Confidence Intervals
ROC Curve
Area Under Curve
Histology
Transplants

ASJC Scopus subject areas

  • Nephrology

Cite this

for the Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators (2017). Cell-Free DNA and active rejection in kidney allografts. Journal of the American Society of Nephrology, 28(7), 2221-2232. https://doi.org/10.1681/ASN.2016091034

Cell-Free DNA and active rejection in kidney allografts. / for the Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators.

In: Journal of the American Society of Nephrology, Vol. 28, No. 7, 01.07.2017, p. 2221-2232.

Research output: Contribution to journalArticle

for the Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators 2017, 'Cell-Free DNA and active rejection in kidney allografts', Journal of the American Society of Nephrology, vol. 28, no. 7, pp. 2221-2232. https://doi.org/10.1681/ASN.2016091034
for the Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators. Cell-Free DNA and active rejection in kidney allografts. Journal of the American Society of Nephrology. 2017 Jul 1;28(7):2221-2232. https://doi.org/10.1681/ASN.2016091034
for the Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators. / Cell-Free DNA and active rejection in kidney allografts. In: Journal of the American Society of Nephrology. 2017 ; Vol. 28, No. 7. pp. 2221-2232.
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abstract = "Histologicanalysis of the allograftbiopsy specimen is the standardmethodused todifferentiate rejection fromother injury in kidney transplants.Donor-derived cell-freeDNA(dd-cfDNA) is a noninvasive test of allograft injury thatmay enablemore 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 negativepredictive values for active rejection at a cutoff of 1.0{\%} dd-cfDNA were 61{\%}and84{\%}, respectively. TheAUCfor discriminatingABMRfromsampleswithoutABMR was 0.87 (95{\%}CI, 0.75 to 0.97). Positive and negative predictive values forABMRat 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, ddcfDNA 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.",
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AU - Weir, Matthew R.

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