Accuracy of Donor-Derived Cell-Free DNA (Dd-cfDNA) Compared with Kidney Allograft Biopsy in the Diagnosis of Allograft Rejection among Adult Filipino Patients in a Tertiary Medical Center

Background: In the Philippines, transplant surveillance primarily involves monitoring common laboratory parameters (creatinine, proteinuria). Allograft biopsy, the gold standard for diagnosing allograft rejection, is not part of surveillance protocols. Donor-derived cell-free DNA (dd-cfDNA) quantifies fragmented DNA that rises in allograft injury. It is non-invasive, has short turnaround time and has been shown to rise prior to laboratory indicators. No study has been done yet among Filipinos involving dd-cfDNA in the diagnosis of allograft rejection since the test became available locally in April 2023. Methods: This is a cross-sectional descriptive study in a tertiary medical center in the Philippines. All data were obtained from electronic medical records. Rejection discrimination was analyzed through area under the curve (AUC), sensitivity (SN), specificity (SP), predictive values, and likelihood ratios. Histologic changes associated with dd-cfDNA levels of >1% were analyzed similarly. Box and Whisker Plots were used to determine differences in dd-cfDNA mean levels in those with and without rejection and between classes of rejection (ABMR and TCMR). Results: Dd-cfDNA significantly discriminates allograft rejection vs no rejection (AUC 0.86, SN 72.73%, SP 100%) and ABMR from non-rejection (AUC 0.94, SN 88.89% SP 100%). It did not discriminate TCMR from non-rejection (AUC 0.55, SN 50, SP 40%). dd-cfDNA level of >1% occurred significantly in: Acute, active ABMR rejection; moderate microvascular inflammation; donor specific antibodies; any microvascular inflammation; chronic active ABMR; and severe peritubular capillary multilayering. Mean dd-cfDNA scores for ABMR is significantly higher (p=0.0394) than those without ABMR. There was no difference in mean levels between rejection and non-rejection (p=0.1790) and TCMR versus non-rejection. Conclusion: Accuracy of dd-cfDNA in diagnosing allograft rejection cannot definitively be concluded based on this study alone. However, findings trend similarly to the DART Cohort and ADMIRAL Study. Dd-cfDNA accuracy values in identifying allograft rejection trend comparably. Mean dd-cfDNA levels in ABMR is significantly higher than in TCMR and in no rejection. Histologic findings associated with dd-cfDNA level of >1% are similar.