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

• Published in: Transplantation proceedings 2024-07, Vol.56 (6), p.1259-1263
• Main Authors: Moein, Mahmoudreza, Settineri, Joseph P., Suleiman, Halima, Sidhu, Jasleen, Papa, Sarah, Coyle, Steven, Dvorai, Reut Hod, Bahreini, Amin, Leggat, John, Saidi, Reza F.
• Format: Article
• Language: English
• Subjects: Adult; Biopsy; Cell-Free Nucleic Acids - blood; Cell-Free Nucleic Acids - genetics; Female; Gene Expression Profiling; Graft Rejection - blood; Graft Rejection - diagnosis; Graft Rejection - genetics; Humans; Kidney - pathology; Kidney Transplantation - adverse effects; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Tissue Donors; Transcriptome
• ISSN: 0041-1345; 1873-2623; 1873-2623
• DOI: 10.1016/j.transproceed.2024.02.023

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. 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. 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. 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.