Introduction: Recently, circulating donor-derived cell-free DNA (dd-cfDNA) has been utilised as a diagnostic biomarker in assessing allograft rejection and renal status. The biomarker is obtained through liquid biopsy. It is a non-invasive test that is relatively simple and safe. However, the accuracy of the test has yet to be established. The main aim of this study was to explore the diagnostic test accuracy using dd-cfDNA in detecting rejection in renal transplantation.
Methods: A systematic review and meta-analysis of diagnostic test accuracy studies were conducted in accordance with PRISMA guidelines, by searching all electronic databases MEDLINE via PubMed, EMBASE, Scopus, and Web of Science. All eligible studies reported sensitivity and specificity outcomes of dd-cfDNA in detecting rejection post-renal transplantation. The data analysis was performed using Review Manager (RevMan) Version 5.4.1 and MetaDTA Version 2.0.
Results: Eight articles were included, comprising 789 samples analysed with a mixture of both antibody-mediated rejection (ABMR) and T cell-mediated rejection (TCMR). The diagnostic performance of dd-cfDNA in detecting allograft rejection revealed a pooled sensitivity of 77% (95% CI: 64.1% - 86.3%) and specificity of 75.5% (95% CI: 69.5% - 81%) in detecting unspecified rejection. A slightly higher pooled sensitivity of 82.7% (95% CI: 73.9% - 88.9%) and specificity of 76.8% (95% CI: 70.1% - 82.5%) were observed in ABMR rejection. Data were inadequate to allow for comparison in TCMR rejection.
Conclusion: This study highlighted the effectiveness of cfDNA in detecting rejection in renal transplantation. Circulating dd-cfDNA can be used as a potential biomarker in transplant recipients to detect the presence of AMR. Future research is required to evaluate the role of dd-cfDNA, in combination with biochemical and histological markers, and to improve diagnostic performance in renal impairment.