Longitudinal Monitoring of Donor-Derived Cell-Free DNA Supports Risk Stratification in Kidney Transplant Recipients With Allograft Dysfunction

The prognostic value of donor-derived cell-free DNA (dd-cfDNA) for long-term kidney allograft outcomes after indication biopsy remains incompletely defined. In this prospective single-center cohort, 106 kidney transplant recipients with 108 indication biopsies were assessed for dd-cfDNA at biopsy and at 7, 30, and 90 days thereafter. dd-cfDNA was analyzed as a continuous, threshold-based, and longitudinal time-dependent variable. Clinical endpoints included ≥30% eGFR decline within 2 years, indication for re-biopsy, and graft failure. Persistent elevation of dd-cfDNA (≥0.5% at 90 days) occurred in 7.4% of patients, with 50% requiring re-biopsy and 37.5% developing graft failure. A single measurement ≥1.0% significantly predicted ≥30% eGFR decline (HR 2.28; 95% CI 1.03–5.05), whereas levels ≥0.5% were less discriminative. In multivariable time-dependent Cox models adjusted for age, sex, time from transplantation to biopsy, baseline eGFR, baseline proteinuria, and Banff domain scores, longitudinal dd-cfDNA remained independently associated with ≥30% eGFR decline (HR 1.68; 95% CI 1.12–2.51), re-biopsy (HR 1.88; 95% CI 1.38–2.55), and graft failure (HR 3.42; 95% CI 2.00–5.86). In conclusion, dd-cfDNA levels, particularly when assessed longitudinally, are associated with adverse allograft outcomes after indication biopsy and may provide relevant prognostic information beyond a single measurement.