Cell-Free DNA and Active Rejection in Kidney Allografts

被引：412

作者：

Bloom, Roy D. ^{[1
,2
]}

Bromberg, Jonathan S. ^{[3
,4
]}

Poggio, Emilio D. ^{[6
]}

Bunnapradist, Suphamai ^{[7
]}

Langone, Anthony J. ^{[8
,9
]}

Sood, Puneet ^{[10
]}

Matas, Arthur J. ^{[11
]}

Mehta, Shikha ^{[12
]}

Mannon, Roslyn B. ^{[12
,13
]}

Sharfuddin, Asif ^{[14
]}

Fischbach, Bernard ^{[15
]}

Narayanan, Mohanram ^{[16
]}

Jordan, Stanley C. ^{[7
,17
]}

Cohen, David ^{[18
]}

Weir, Matthew R. ^{[5
]}

Hiller, David ^{[19
]}

Prasad, Preethi ^{[20
]}

Woodward, Robert N. ^{[21
]}

Grskovic, Marica ^{[21
]}

Sninsky, John J. ^{[21
]}

Yee, James P. ^{[20
]}

Brennan, Daniel C. ^{[22
]}

机构：

[1] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA

[2] Penn Kidney Pancreas Transplant Program, Philadelphia, PA USA

[3] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA

[4] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA

[5] Univ Maryland, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21201 USA

[6] Cleveland Clin, Dept Hypertens & Nephrol, Cleveland, OH 44106 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[8] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[9] Vet Affairs Hosp, Med Specialties Clin, Renal Transplant Program, Nashville, TN USA

[10] Univ Pittsburgh, Med Ctr, Thomas Starzl Transplant Inst, Pittsburgh, PA USA

[11] Univ Minnesota, Dept Surg, Div Transplantat, Box 242 UMHC, Minneapolis, MN 55455 USA

[12] Univ Alabama Birmingham, Sch Med, Dept Med, Div Nephrol, Birmingham, AL USA

[13] Univ Alabama Birmingham, Sch Med, Div Transplantat, Birmingham, AL USA

[14] Indiana Univ Sch Med, Dept Med, Div Nephrol & Transplant, Indianapolis, IN 46202 USA

[15] Baylor Res Inst, Dallas, TX USA

[16] Texas A&M Hlth Sci Ctr, Coll Med, Div Nephrol & Hypertens, Temple, TX USA

[17] Cedars Sinai Med Ctr, Div Nephrol, Los Angeles, CA 90048 USA

[18] Columbia Univ, Med Ctr, Dept Surg, New York, NY USA

[19] CareDx Inc, Biostat, Brisbane, CA USA

[20] CareDx Inc, Clin Res, Brisbane, CA USA

[21] CareDx Inc, Res & Dev, Brisbane, CA USA

[22] Washington Univ, Sch Med, St Louis, MO USA

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2017年 / 28卷 / 07期

关键词：

TRANSPLANT RECIPIENTS; UNIVERSAL BIOMARKER; QUANTIFICATION; PLASMA; ASSAY;

D O I：

10.1681/ASN.2016091034

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2221 / 2232

页数：12

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