The clinical value of donor-derived cell-free DNA measurements in kidney transplantation

Neetika Garg; Didier A Mandelbrot; Sandesh Parajuli; Fahad Aziz; Brad C Astor; Anil Chandraker; Arjang Djamali

doi:10.1016/j.trre.2021.100649

The clinical value of donor-derived cell-free DNA measurements in kidney transplantation

Transplant Rev (Orlando). 2021 Dec;35(4):100649. doi: 10.1016/j.trre.2021.100649. Epub 2021 Aug 21.

Authors

Neetika Garg¹, Didier A Mandelbrot², Sandesh Parajuli³, Fahad Aziz⁴, Brad C Astor⁵, Anil Chandraker⁶, Arjang Djamali⁷

Affiliations

¹ Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address: ngarg@medicine.wisc.edu.
² Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address: damandel@medicine.wisc.edu.
³ Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address: sparajuli@medicine.wisc.edu.
⁴ Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address: faziz@wisc.edu.
⁵ Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address: bcastor@medicine.wisc.edu.
⁶ Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: achandraker@bwh.harvard.edu.
⁷ Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health Madison, WI, USA. Electronic address: axd@medicine.wisc.edu.

PMID: 34507254
DOI: 10.1016/j.trre.2021.100649

Abstract

Early diagnosis is critical to minimizing the damage rejection can do to the transplanted kidney. Donor-derived cell-free DNA (dd-cfDNA) represents non-encapsulated fragmented DNA that is continuously shed into the bloodstream from the allograft undergoing injury, with a half-life of about 30 min. This article reviews the available evidence regarding the diagnostic value of dd-cfDNA in kidney transplantation, as a result of which two assays, Allosure and Prospera, have garnered Medicare approval. We provide information on important scenarios and contexts including antibody-mediated rejection, T-cell mediated rejection, pre-test probability of rejection, timing of the test, repeat transplants, and background cell-free DNA levels to help our understanding of the test characteristics and utility of these assays in clinical practice. Data on multimodality assays including gene expression profiles and serial monitoring of dd-cfDNA in high risk situations are emerging.

Keywords: Biomarker; Donor-derived cell-free DNA; Kidney transplant; Rejection.

Publication types

Review

MeSH terms

Aged
Cell-Free Nucleic Acids*
Graft Rejection / diagnosis
Humans
Kidney Transplantation*
Medicare
Tissue Donors
United States

Substances

Cell-Free Nucleic Acids