Evaluating the Diagnostic Utility of dd-cfDNA in Renal Allograft Surveillance: A Single-Center Perspective.

Background

Donor-derived cell-free DNA (dd-cfDNA) testing offers a non-invasive approach for monitoring allograft health in transplant recipients. However, its diagnostic performance and clinical utility remain insufficiently characterized across diverse populations.

Objectives

This study assesses concordance between dd-cfDNA, donor-specific antibody (DSA) testing, and biopsy, while also comparing two commercial assays (AlloSure and Prospera) in kidney and pancreas transplant recipients.

Methods

We retrospectively analyzed 271 transplant patient records from 2019 to 2024 at our institution, focusing on dd-cfDNA testing. Statistical analyses evaluated assay performance in relation to DSA and biopsy results. The impact of multi-organ transplantation (MOT) on dd-cfDNA levels was also assessed.

Results

In our predominantly Caucasian cohort (61.5%) with a mean age of 53 years, increased levels of dd-cfDNA were significantly associated with DSA positivity, particularly within the Prospera group (p = 0.002), and were particularly higher in patients with HLA class II DSA. Both assays showed a limited correlation with biopsy-confirmed rejection. AlloSure had high specificity (80%) but low sensitivity (19%), whereas Prospera showed higher sensitivity (75%) with moderate specificity (60%). Dd-cfDNA levels were elevated in MOT recipients in a vendor-dependent manner.

Conclusions

Our findings highlight the differing clinical strengths of dd-cfDNA assays: AlloSure demonstrates greater preference for ruling out rejection, whereas Prospera appears better suited for early detection. Dd-cfDNA interpretation in MOT recipients warrants cautious consideration. Overall, tailoring assay selection and optimizing diagnostic thresholds to clinical context may enhance transplant surveillance and patient management strategies.