dd-cfDNA as a predictor of allograft functional decline in kidney transplant recipients

Results from a single-center prospective study evaluating donor-derived cell-free DNA (dd-cfDNA) as a predictor of allograft functional decline beyond standard Banff histology in 78 kidney transplant recipients were presented by Eunjeong Kwon at the 31st International Congress of The Transplantation Society (TTS), September 20–23, 2026, Sydney, AU. dd-cfDNA was measured as donor fraction equivalent (DFE, %) and donor quantity score (DQS, copies/mL).

Key data: Peritubular capillaritis was the only independent Banff predictor of dd-cfDNA elevation (dy/dx = 0.245, p < 0.001), whereas tubulointerstitial lesions showed no independent effect. dd-cfDNA demonstrated diagnostic performance for microvascular inflammation (MVI) ≥2 (DFE area under the curve [AUC], 0.83) and antibody-mediated rejection (ABMR; DFE AUC, 0.85). DFE >1% was associated with a ~3-fold higher urine protein-to-creatinine ratio (uPCR) vs dd-cfDNA ≤1% throughout 3.5 years of follow-up (p = 0.003); uPCR was 2.6-fold higher when excluding the graft-failure case (p = 0.007).

Key learning: In this study, peritubular capillaritis was the only independent Banff predictor of dd-cfDNA elevation, indicating dd-cfDNA primarily reflects microvascular endothelial injury. Moreover, dd-cfDNA predicted higher proteinuria even when excluding the graft-failure case, suggesting that dd-cfDNA elevation may reflect persistent microvascular injury preceding overt allograft dysfunction.