The use of plasma donor-derived, cell-free DNA to monitor acute rejection after kidney transplantation

被引:72
作者
Gielis, Els M. [1 ]
Ledeganck, Kristien J. [1 ]
Dendooven, Amelie [2 ]
Meysman, Pieter [3 ,4 ]
Beirnaert, Charlie [3 ,4 ]
Laukens, Kris [3 ,4 ]
De Schrijver, Joachim [5 ]
Van Laecke, Steven [6 ]
Van Biesen, Wim [6 ]
Emonds, Marie-Paule [7 ]
De Winter, Benedicte Y. [1 ]
Bosmans, Jean-Louis [1 ,8 ]
Del Favero, Jurgen [5 ]
Abramowicz, Daniel [1 ,8 ]
机构
[1] Univ Antwerp, Lab Expt Med & Pediat, Antwerp, Belgium
[2] Antwerp Univ Hosp, Dept Pathol, Antwerp, Belgium
[3] Univ Antwerp, Antwerp Univ Hosp, Biomed Informat Res Network Antwerp Biomina, Antwerp, Belgium
[4] Univ Antwerp, Dept Math & Comp Sci, Adv Database Res & Modelling ADReM, Antwerp, Belgium
[5] Multiplicom NV, Part Agilent Technol, Niel, Belgium
[6] Ghent Univ Hosp, Dept Nephrol, Renal Div, Ghent, Belgium
[7] Belgian Red Cross Flanders, Histocompatibil & Immunogenet Lab, Mechelen, Belgium
[8] Antwerp Univ Hosp, Dept Nephrol & Hypertens, Antwerp, Belgium
关键词
acute kidney rejection; biomarker; donor-derived cell-free DNA; kidney transplantation; HEMODIALYSIS; CLEARANCE; BIOMARKER; ASSAY;
D O I
10.1093/ndt/gfz091
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Background. After transplantation, cell-free deoxyribonucleic acid (DNA) derived from the donor organ (ddcfDNA) can be detected in the recipient's circulation. We aimed to investigate the role of plasma ddcfDNA as biomarker for acute kidney rejection. Methods. From 107 kidney transplant recipients, plasma samples were collected longitudinally after transplantation (Day 1 to 3 months) within a multicentre set-up. Cell-free DNA from the donor was quantified in plasma as a fraction of the total cell-free DNA by next generation sequencing using a targeted, multiplex polymerase chain reaction-based method for the analysis of single nucleotide polymorphisms. Results. Increases of the ddcfDNA% above a threshold value of 0.88% were significantly associated with the occurrence of episodes of acute rejection (P=0.017), acute tubular necrosis (P=0.011) and acute pyelonephritis (P=0.032). A receiver operating characteristic curve analysis revealed an equal area under the curve of the ddcfDNA% and serum creatinine of 0.64 for the diagnosis of acute rejection. Conclusions. Although increases in plasma ddcfDNA% are associated with graft injury, plasma ddcfDNA does not outperform the diagnostic capacity of the serum creatinine in the diagnosis of acute rejection.
引用
收藏
页码:714 / 721
页数:8
相关论文
共 25 条
[1]   Digital Droplet PCR for Rapid Quantification of Donor DNA in the Circulation of Transplant Recipients as a Potential Universal Biomarker of Graft Injury [J].
Beck, Julia ;
Bierau, Sarah ;
Balzer, Stefan ;
Andag, Reiner ;
Kanzow, Philipp ;
Schmitz, Jessica ;
Gaedcke, Jochen ;
Moerer, Onnen ;
Slotta, Jan E. ;
Walson, Philip ;
Kollmar, Otto ;
Oellerich, Michael ;
Schuetz, Ekkehard .
CLINICAL CHEMISTRY, 2013, 59 (12) :1732-1741
[2]   Cell-Free DNA and Active Rejection in Kidney Allografts [J].
Bloom, Roy D. ;
Bromberg, Jonathan S. ;
Poggio, Emilio D. ;
Bunnapradist, Suphamai ;
Langone, Anthony J. ;
Sood, Puneet ;
Matas, Arthur J. ;
Mehta, Shikha ;
Mannon, Roslyn B. ;
Sharfuddin, Asif ;
Fischbach, Bernard ;
Narayanan, Mohanram ;
Jordan, Stanley C. ;
Cohen, David ;
Weir, Matthew R. ;
Hiller, David ;
Prasad, Preethi ;
Woodward, Robert N. ;
Grskovic, Marica ;
Sninsky, John J. ;
Yee, James P. ;
Brennan, Daniel C. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2017, 28 (07) :2221-2232
[3]   Antibody-mediated renal allograft rejection: Diagnosis and pathogenesis [J].
Colvin, Robert B. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (04) :1046-1056
[4]   Acute kidney injury in kidney transplantation [J].
Cooper, James E. ;
Wiseman, Alexander C. .
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION, 2013, 22 (06) :698-703
[5]   Circulating Cell-Free DNA Enables Noninvasive Diagnosis of Heart Transplant Rejection [J].
De Vlaminck, Iwijn ;
Valantine, Hannah A. ;
Snyder, Thomas M. ;
Strehl, Calvin ;
Cohen, Garrett ;
Luikart, Helen ;
Neff, Norma F. ;
Okamoto, Jennifer ;
Bernstein, Daniel ;
Weisshaar, Dana ;
Quake, Stephen R. ;
Khush, Kiran K. .
SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (241)
[6]   KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients [J].
Eckardt, Kai-Uwe ;
Kasiske, Bertram L. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2009, 9 :S1-S155
[7]   Non-invasive Biomarkers of Acute Rejection in Kidney Transplantation: Novel Targets and Strategies [J].
Eikmans, Michael ;
Gielis, Els M. ;
Ledeganck, Kristien J. ;
Yang, Jianxin ;
Abramowicz, Daniel ;
Claas, Frans F. J. .
FRONTIERS IN MEDICINE, 2019, 5
[8]   International variation in the interpretation of renal transplant biopsies: Report of the CERTPAP Project [J].
Furness, PN ;
Taub, N .
KIDNEY INTERNATIONAL, 2001, 60 (05) :1998-2012
[9]   Cell-Free DNA as a Noninvasive Acute Rejection Marker in Renal Transplantation [J].
Garcia Moreira, Vanessa ;
Prieto Garcia, Belen ;
Baltar Martin, Jose M. ;
Ortega Suarez, Francisco ;
Alvarez, Francisco V. .
CLINICAL CHEMISTRY, 2009, 55 (11) :1958-1966
[10]   Cell-Free DNA: An Upcoming Biomarker in Transplantation [J].
Gielis, E. M. ;
Ledeganck, K. J. ;
De Winter, B. Y. ;
Del Favero, J. ;
Bosmans, J. -L. ;
Claas, F. H. J. ;
Abramowicz, D. ;
Eikmans, M. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2015, 15 (10) :2541-2551