Real-world utilization patterns and association of dd-cfDNA with biopsy and rejection

Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for allograft injury in kidney transplant recipients. This single-center study aimed to evaluate the clinical indications for dd-cfDNA testing, its association with biopsy findings, and the comparative utility of dd-cfDNA expressed as a percentage versus absolute copy number.

A retrospective analysis was conducted of 571 dd-cfDNA measurements from 313 kidney transplant recipients at the Charité Berlin Transplant Center from May 2020 to May 2025. The clinical indications for testing, biopsy, and rejection predictors were assessed using multivariable logistic regression and linear regression.

Elevated creatinine (29%), elevated urine albumin-to-creatinine ratio (UACR, 10%), donor-specific antibody positivity (10%), history of rejection (9%), immunosuppression reduction (5%), and combined reasons (38%) were the most frequent indications for dd-cfDNA testing. Elevated UACR was the only independent predictor of biopsy (odds ratio [OR], 3.02; 95% confidence interval [CI], 1.39-6.58; p = 0.005). In the biopsy cohort, the dd-cfDNA percentage (OR, 5.46; 95% CI, 2.89-13.70; p = 0.0035) and copies/mL (OR, 7.05; 95% CI, 1.01-21.09; p = 0.0062) independently predicted rejection. ROC analysis indicated good discrimination of rejection for both copies/mL (AUC, 0.781) and percentage (AUC, 0.820). DCA revealed that both dd-cfDNA formats offered greater net clinical benefits for rejection prediction than the conventional markers.

Although biopsy decisions primarily rely on conventional clinical parameters, dd-cfDNA can independently identify rejection and improve decision-making when integrated into multimodal post-transplant monitoring strategies.