Diagnostic Test Accuracy of Detecting Donor-Derived Cell-Free DNA in Renal Transplant Rejection: A Systematic Review...

Circulating donor-derived cell-free DNA (dd-cfDNA) has emerged as a noninvasive biomarker for detecting allograft rejection and assessing renal status. While promising, its diagnostic test accuracy (DTA) remains unclear. This study aimed to evaluate the DTA of dd-cfDNA in identifying rejection following renal transplantation.

A systematic review and meta-analysis of DTA studies were conducted following PRISMA guidelines. Electronic databases (MEDLINE via PubMed, Embase, Scopus and Web of Science) were searched comprehensively for studies reporting the sensitivity and specificity of dd-cfDNA in detecting renal allograft rejection. Data were analysed using Review Manager (RevMan) 5.4.1 and MetaDTA 2.0.

Thirteen studies were included, comprising 2214 samples across various rejection types, including antibody-mediated rejection (ABMR) and T cell-mediated rejection (TCMR). Meta-analysis revealed pooled sensitivities and specificities for detecting unspecified rejection of 61.1% (95% CI: 48.2%-74.8%) and 83.0% (95% CI: 76.3%-88.5%), respectively. For ABMR, pooled sensitivity increased to 75.6% (95% CI: 61.7%-86.4%) with a specificity of 82.1% (95% CI: 71.4%-88.8%). Meta-regression analysis using a dd-cfDNA threshold of 1% demonstrated comparable sensitivity and specificity for the detection of biopsy-proven rejection and ABMR, yielding estimates consistent with the overall pooled results. Insufficient data were available to allow for analytical comparison in TCMR. The area under the curve (AUC) was highest in the ABMR group.

dd-cfDNA shows potential as a diagnostic biomarker, particularly for ABMR in renal transplantation. Further studies integrating dd-cfDNA with biochemical and histological markers are recommended to enhance diagnostic precision.