Application of Combined Donor-Derived Cell-Free DNA and Transcriptome in Diagnosis of Kidney Transplant Rejection.

Background: Transcriptomic kidney profile testing and donor-derived cell-free DNA (dd-cfDNA) testing are new methods shown to provide early markers of graft inflammation during the post-transplant period. This study focused on utilizing clinical data to evaluate the application of these tests in detecting transplant rejection by comparing tests results to biopsy reports.

Material And Methods: We conducted a retrospective analysis of a prospectively collected database of all adult kidney transplant patients at SUNY Upstate Medical Hospital from 1 January 2014 to 1 December 2022. Inclusion criteria were patients with concurrent transcriptomic kidney profile test and kidney biopsy results.

Results: Biopsies identified 33 kidney transplant rejections. For diagnosis of kidney rejection, transcriptomic kidney profile testing had a 52.83% positive predictive value and 92.77% negative predicative value, while dd-cfDNA testing had a 54.83% positive predictive value and 86.45% negative predictive value. Transcriptomic kidney profile testing showed an 82.35% sensitivity and 75.49% specificity, while dd-cfDNA testing showed a 56.66% sensitivity and 85.56% specificity. Positive transcriptomic kidney profile and dd-cfDNA tests detected 51.51% of rejections. Combined negative tests were observed in 70.21% of biopsies without rejection.

Conclusions: Despite certain discrepancies and limitations, we believe transcriptomic profile testing and dd-cfDNA testing are useful for detecting early-stage rejections and can guide patient care. Additionally, dd-cfDNA testing avoids invasive screening biopsies. Following negative test results, the probability patients are not having rejection is 86.45%. The transcriptomic profile test's high sensitivity and specificity allow possible detection of transplant rejections that may have otherwise not been identified by biopsy.