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Liquid Biopsies to Monitor Solid Organ Transplant Function

A Review of New Biomarkers

Verhoeven, Jeroen G. H. P., MD*,†; Boer, Karin, PhD*,†; Van Schaik, Ron H. N., PhD; Manintveld, Olivier C., MD, PhD†,§; Huibers, Manon M. H., PhD; Baan, Carla C., PhD*,†; Hesselink, Dennis A., MD, PhD*,†

doi: 10.1097/FTD.0000000000000549
Review Article

Abstract: Despite modern immunosuppressive therapy, allograft rejection remains a major cause of solid organ transplant dysfunction. For clinical care, organ transplant function is routinely monitored by measuring biomarkers that, depending on the organ transplanted, include serum creatinine, N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP), and aspartate aminotransferase. All can be measured easily in clinical chemistry laboratories. The main problem with these biomarkers is that they have a low sensitivity for the detection of allograft damage and are nonspecific for the detection of allograft rejection. To diagnose rejection, histologic examination of grafted tissue is necessary, which requires an invasive biopsy procedure. There is thus an unmet need in transplantation medicine for biomarkers that are specific for rejection, identify graft injury at an early stage, and may eventually overcome the need for a transplant biopsy. Recently, tremendous progress in the field of biomarkers has been made. In this narrative review, the potential of donor-derived cell-free DNA (ddcfDNA), cell-free nucleosomes, and extracellular vesicles to act as next-generation biomarkers for solid organ transplant is discussed. Based on the fact that cell content is released during rejection, these markers could serve as very specific biomarkers for allograft injury and rejection. These markers have the potential to improve rejection monitoring, evaluate the response to antirejection therapy, and may decrease the need for invasive procedures.

*Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam;

Division of Nephrology and Transplantation, Rotterdam Transplant Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam;

Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam;

§Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam; and

Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.

Correspondence: Jeroen G. H. P. Verhoeven, MD, Department of Internal Medicine, Division of Nephrology, Transplantation Rotterdam Transplant Group, Erasmus MC, University Medical Center Rotterdam, Room Na-524, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands (e-mail: j.verhoeven@erasmusmc.nl).

D. A. Hesselink has received grant support, lecture and consulting fees from Astellas Pharma and Chiesi Pharmaceuticals, as well as a lecture fee from Hikma Pharma and grand support from Bristol Myers-Squibb. The remaining authors declare no conflict of interest.

Received May 07, 2018

Accepted June 07, 2018

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.