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

Area of Science:

• Transplantation immunology
• Biomarker discovery
• Genomics

Background:

• Acute rejection diagnosis often requires invasive biopsies.
• Noninvasive biomarkers like donor-derived cell-free DNA (dd-cfDNA) are sought for early detection.
• Limited data exists on ethnic variations in dd-cfDNA levels during rejection.

Purpose of the Study:

• To investigate ethnic differences in dd-cfDNA values at the time of graft rejection.
• To compare dd-cfDNA performance using established cutoffs (0.5% and 1%) across racial and ethnic groups.
• To assess dd-cfDNA's utility in diagnosing specific rejection types, particularly antibody-mediated rejection (AMR).

Main Methods:

• Single-center retrospective observational study.
• Paired analysis of graft biopsies and preceding dd-cfDNA measurements.
• Stratification of recipients into White, Black, and Hispanic groups for comparative analysis.

Main Results:

• False negative rates for rejection were 13% (0.5% cutoff) and 22% (1% cutoff).
• False positive rate was 38.4%.
• dd-cfDNA demonstrated robust detection of AMR in Black recipients (65.5% of rejection cases) and accurate diagnosis in 52.8% of AMR cases.

Conclusions:

• Donor-derived cell-free DNA (dd-cfDNA) is a valuable tool for diagnosing acute rejection across diverse ethnic groups.
• The performance of dd-cfDNA in detecting rejection, particularly AMR, is robust in Black recipients.
• Findings support the use of dd-cfDNA as a noninvasive adjunct to biopsy for monitoring transplant health.