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

## TL;DR

This study evaluates how well dd-cfDNA tests detect kidney and pancreas transplant rejection, comparing two commercial assays and their performance with biopsy and antibody testing.

## Contribution

The study provides a single-center comparison of two dd-cfDNA assays in kidney and pancreas transplant recipients, highlighting their diagnostic strengths and limitations.

## Key findings

- Prospera showed higher sensitivity (75%) for detecting rejection compared to AlloSure (19%).
- Dd-cfDNA levels were significantly associated with HLA class II DSA positivity in the Prospera group.
- AlloSure had high specificity (80%) but low sensitivity, making it better for ruling out rejection.

## Abstract

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.