Analytical Validation of a Single-nucleotide Polymorphism-based Donor-derived Cell-free DNA Assay for Detecting Rejection in Kidney Transplant Patients

Transplantation
Yücel AltuğAllison Ryan

Abstract

Early detection of rejection in kidney transplant recipients holds the promise to improve clinical outcomes. Development and implementation of more accurate, noninvasive methods to detect allograft rejection remain an ongoing challenge. The limitations of existing allograft surveillance methods present an opportunity for donor-derived cell-free DNA (dd-cfDNA), which can accurately and rapidly differentiate patients with allograft rejection from patients with stable organ function. This study evaluated the analytical performance of a massively multiplexed polymerase chain reaction assay that targets 13 962 single-nucleotide polymorphisms, characterized and validated using 66 unique samples with 1064 replicates, including cell line-derived reference samples, plasma-derived mixtures, and transplant patient samples. The dd-cfDNA fraction was quantified in both related and unrelated donor-recipient pairs. The dd-cfDNA assay showed a limit of blank of 0.11%, a limit of detection and limit of quantitation of 0.15% for unrelated donors, and limit of blank of 0.23%, a limit of detection and limit of quantitation of 0.29% for related donors. All other metrics (linearity, accuracy, and precision) were observed to be equivalent between unr...Continue Reading

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Citations

Feb 12, 2020·Transplantation·Marica GrskovicRobert N Woodward
Dec 28, 2019·Transplantation·Yücel AltuğAllison Ryan
May 20, 2020·Journal of Clinical Medicine·Charat ThongprayoonWisit Cheungpasitporn
May 25, 2020·The Journal of Applied Laboratory Medicine·Michael OellerichPhilip D Walson
Feb 2, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Abdulla EhlayelIsa F Ashoor
Feb 11, 2021·Transplantation Direct·Rohan S PaulMuralidaran Jagadeesan
Jan 18, 2021·Néphrologie & thérapeutique·Yang ZhouTingya Jiang
Aug 1, 2020·Transplantation·Edward John Filippone, John L Farber
Apr 30, 2021·Néphrologie & thérapeutique·Elisabet Van Loon, Maarten Naesens
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Methods Mentioned

BETA
biopsies
biopsy
PCR
blood draws
genotyping

Software Mentioned

Python
Python Software Foundation

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