Monitoring kidney transplant recipients for evidence of rejection is essential to mitigate the risk of graft failure. Donor-derived cell-free DNA (dd-cfDNA) is a dynamic marker of cell turnover in the allograft that can be used as a surrogate marker of allograft injury and allows for noninvasive monitoring (1⇓–3). Quantification of the dd-cfDNA fraction requires differentiation of donor and recipient genomes. Early methodologies relied on detection of genes found on the Y chromosome, which limited use to women recipients with men organ donors, or genome sequencing, which required separate genotyping of the donor (4). Targeted next generation sequencing (NGS) techniques use panels of single-nucleotide polymorphisms (SNPs) to differentiate dd-cfDNA from recipient cell-free DNA. Currently available NGS platforms for dd-cfDNA fraction quantification include AlloSure (CareDx, Inc., Brisbane, CA) and Prospera (Natera, Inc., San Carlos, CA). Although both rely on panels of SNPs, their methodologies are distinct. AlloSure previously used a panel of 266 SNPs selected from across all 22 somatic chromosomes with sufficient separation and low linkage (5), and it has since been updated to include 405 SNPs as noted in the recent publication by Melancon et al. (6). Prospera uses 13,392 SNPs concentrated across four chromosomes (3). The latter was adapted for use in kidney transplantation from an approach developed for noninvasive prenatal monitoring. Both of these tests allow for the measurement of dd-cfDNA in kidney transplant recipients without requiring knowledge of donor genotypes.
In his recent publication, Melancon et al. (6) reported results from simultaneous AlloSure and Prospera tests performed in 76 patients …
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