Racial Variation of Donor-Derived Cell-Free DNA in Kidney Transplant Recipients

Introduction: There is a need for a noninvasive, affordable, sensitive, and specific biomarker to diagnose early acute rejection, to negate the need for frequent biopsies. Dd-cfDNA is a powerful adjunct yet there is limited data on the ethnic differences in its values. There is anecdotal evidence that dd-cfDNA values at rejection may be higher in Black as compared to non-Black recipients. This study aims to add to this literature while defining such variability and comparing it to previously validated cutoffs for dd-cfDNA of 0.5% or 1%.

Design: This was a single-center retrospective observational study of patients who underwent graft biopsies with a preceding, paired, dd-cfDNA value. Recipients were separated into White, Black, and Hispanic racial and ethnic groups, and dd-cfDNA values at rejection versus nonrejection were compared.

Results: With 0.5% and 1% cutoffs, false negative rates for rejection were 13% and 22%, respectively. The false positive rate was 38.4%. 12.2% of Black recipients, 11.8% of Hispanic recipients, and 44% of White recipients had rejection with a negative AlloSure^®. Values >0.5% corresponded to histologic rejection in 61.5% of Black, 66.7% of White, and 56.3% of Hispanic recipients. Antibody-mediated rejection occurred in 65.5% of rejection cases in Black recipients, while exhibiting the lowest rate of T-cell-mediated rejection. Dd-cfDNA values gave an accurate diagnosis of rejection in 52.8% of recipients with AMR versus 19.3% in TCMR.

Conclusion: This study demonstrated that dd-cfDNA was applicable to Black recipients with a robust ability to detect antibody-mediated rejection, as compared to White and Hispanic recipients.