Introduction: Early post-transplant elevations in dd-cfDNA, even in the absence of histologic rejection or other overt pathology, have been suggested to carry a riskof adverse outcomes among solid organ transplant recipients. We investigated this association among kidney transplant recipients enrolled in the Kidneyallograft Outcomes AlloSure Registry (KOAR, NCT03326076).

Methods: To assess the impact of early post-transplant dd-cfDNA elevations, we evaluated the incidence of a clinical composite that included biopsy-provenrejection (BPAR), detection of de novo donor specific antibodies (dnDSA) and return to dialysis in patients with and without median dd-cfDNA >1% over the first100 days post-transplant. Patients with events before day 100 were excluded. Univariate and multivariate analyses were performed.

Results: 51 of 1296 patients (3.9%) had a median dd-cfDNA ≥1.0% during the first 100 days post-transplant. In a univariate model, these patients had asignificantly higher risk of the experiencing both the composite outcome and each individual component during the first post-transplant year (Figure 1). In a multivariate Cox proportional hazards model that included recipient age, delayed graft function, donor type (living vs deceased), and recipient sensitization,only 100-day median dd-cfDNA elevation ≥1.0% was a statistically significant predictor of the composite outcome, with a hazard ratio of 2.99 (95% CI: 1.59 -5.61, p < 0.005) (Table 1).

Conclusions: Our findings suggest that early post-transplant elevations in dd-cfDNA among kidney transplant recipients, even in the absence of clearimmunologic or histologic correlates, identify a population of patients at risk for adverse clinical outcomes during the first post-transplant year. Molecular risk-stratification using dd-cfDNA may have implications for clinical surveillance and therapeutic management of these patients.