Donor-derived cell-free DNA test may help detect graft rejection in kidney transplant recipients
BOSTON — A test that uses donor-derived cell-free DNA accurately discriminated rejection from non-rejection in kidney transplant recipients and was particularly effective in the discrimination of antibody-mediated rejection, according to research presented at the American Transplant Congress.
“Our work suggests that the donor-derived cell-free DNA test may be useful to discriminate rejection in cases that are suspicious for, yet not diagnostic for, antibody-mediated rejection under current diagnostic criteria, which requires detection of donor-specific antibodies,” Edmund Huang, MD, of Cedars Sinai Medical Center in Los Angeles, told Healio/Nephrology.
To externally validate previous results that suggested such a test was useful, researchers considered 63 kidney transplant recipients who had an assessment of donor-derived cell-free DNA within 30 days of an allograft biopsy. Through biopsies interpreted using Banff 2013 criteria, researchers assessed rejection in the setting of graft dysfunction or donor-specific antibodies (43% had donor-specific antibodies).
Biopsies determined 54% of all participants had rejection, with researchers finding that the percentage of donor-derived cell-free DNA was higher among patients with antibody-mediated rejection (median 1.35%; IQR: 1.10 to 1.90) than those with no rejection (median, 0.38%; IQR: 0.26 to 1.10) and cell-mediated rejection (median, 0.27%; IQR: 0.19 to 1.30).
It was further observed that the area under the receiver operating characteristic curve for any rejection was 0.71 and that a donor-derived cell-free DNA threshold of at least 0.74% was associated with a sensitivity of 79.4%, a specificity of 72.4%, a positive predictive value of 77.1% and a negative predictive value of 75%.
When examining antibody-mediated rejection, researchers observed that the area under the curve was 0.82 and that a donor-derived cell-free DNA at least 0.74% yielded a sensitivity of 100%, a specificity of 71.8%, a positive predictive value of 68.6% and a negative predictive value of 100%.
“The donor-derived cell-free DNA test is particularly valuable when rejection is suspected, as it can bolster a clinician's recommendation to pursue kidney biopsy, provide additional context for interpretation of biopsy findings and support clinical diagnoses in borderline or suspicious cases,” Huang said. “I am looking forward to further work, which is currently ongoing, that will study whether levels of donor-derived cell-free DNA can predict future graft outcomes.” – by Melissa J. Webb
Huang E, et al. Paper A133. Presented at: American Transplant Congress. June 1-5, 2019; Boston.
Disclosure: Huang reports consulting fees and clinical trial grant support from CareDx Inc.