Donor-Derived Cell Free DNA: Is It All the Same?

Abstract

BackgroundClinical utility of donor-derived, cellfree DNA (dd-cfDNA) in transplantation has been extensively reviewed, supporting its use as a surveillance tool for the early and accurate detection of allograft injury. Yet studies comparing different assay methods have been lacking.MethodsPaired sampling of commercially available dd-cfDNA (AlloSure and Prospera) was compared and examined against histology and manufacturer guidance. A total of 76 patients were prospectively assessed, with 11 biopsy sample–proven rejections (antibody-mediated rejection, n=2; T cell–mediated rejection, n=9).ResultsProspera demonstrated larger measurements of dd-cfDNA in comparison with AlloSure, but this was NS (P=0.12). At current manufacturer recommended diagnostic cutoffs, there was no significant difference in sensitivity, specificity, negative predictive value, or positive predictive value of AlloSure versus Prospera in detecting rejection. AlloSure demonstrated a significantly shorter turnaround time (P=0.01) from blood draw to patient result.ConclusionsAlthough dd-cfDNAs are similar, they are not the same. Extensive evidence for dd-cfDNA interpretation remains the key to building clinical utility when considering clinical implementation, and remaining consistent to a single platform is important when creating data comparisons.

Donor-Derived Cell-Free DNA (ddcf-DNA) and Acute Antibody-Mediated Rejection in Kidney Transplantation

“…Two NGS assays, AlloSure (Care Dx, Inc., Brisbane, CA, USA) [ 4 , 5 ] and Prosepera (Natera, Inc., San Carlos, CA, USA) [ 6 ] target 266 SNPs and 1392 SNPs, respectively. Melancon et al compare the performance of these assays in a small single-center study involving 76 transplant recipients [ 10 ]. The study participants had a paired blood draw with one sample being allocated to each assay.…”

Emerging role of cell-free DNA in kidney transplantation

“…There are no standardized assays to be used for transplantation, in terms of the number of SNPs. The commercially available assays using NGS technology so far are Allosure, (CareDx, Brisbane, CA, United States), which targets 266 SNPs[ 34 ]; Prospera, (Natera Inc, San Carlos, CA, United States), which targets 13392 SNPs[ 35 ], Viracor Transplant Rejection Allograft Check (TRAC) combined with TruGraf, and (Eurofins Viracor, (Lee's Summit, MO, United States), which targets 70000 SNPs[ 36 ]. There is one study that compared the results of two commonly available commercial assays in United States; Allosure and Natera, involving 76 kidney transplant recipients.…”

“…There is one study that compared the results of two commonly available commercial assays in United States; Allosure and Natera, involving 76 kidney transplant recipients. It found no significant differences in the test results for predicting rejection or other test characteristics, but found some differences in the test result turnaround time[ 36 , 37 ]. The recipient genotype is determined at each SNP and the relative fraction of dd-cfDNA is computed using custom bioinformatics tools.…”

Early Experience Using Donor-derived Cell-free DNA for Surveillance of Rejection Following Simultaneous Pancreas and Kidney Transplantation

“…5-9 In kidney transplantation, a dd-cfDNA cutoff of 0.5% is typically used to differentiate normal from allograft injury. 10 Relative change values can also be utilized—increases of <61% of dd-cfDNA may be because of normal variation, but greater increases should raise suspicion of rejection. 11…”