Integrating Donor Derived Cell-Free DNA Fraction and Absolute Quantification for Enhanced Rejection Diagnosis in Kidney Transplant Recipients

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2025 Feb 13

PMID 39941167

Authors

Weijian Nie

Yan Wang

Qian Fu

Chenglin Wu

Ronghai Deng

Xiaolin Yu

Caiguo Ye

Xiangjun Liu

Bowen Xu

Pingping Sun

Longshan Liu

Jun Li

Huanxi Zhang

Changxi Wang

Affiliations

Soon will be listed here.

Abstract

This study aimed to assess the diagnostic accuracy of combining donor-derived cell-free DNA (dd-cfDNA) fraction and absolute quantification in detecting kidney allograft rejection. A prospective study was conducted from December 2019 to April 2021 at the First Affiliated Hospital of Sun Yat-sen University. Kidney transplant recipients who underwent biopsy, including cases of T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), and borderline rejection, were included. dd-cfDNA fraction and absolute concentrations were measured, and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) analysis. The double-positive and double-negative methods were applied to assess performance. A total of 50 kidney transplant recipients were included. The dd-cfDNA fraction cutoff of 1.08% achieved 93.33% sensitivity and 91.43% specificity (AUC = 0.95), with an NPV of 96.97% and a PPV of 82.35%. The absolute dd-cfDNA threshold of 32 cp/mL yielded 80.00% sensitivity and 71.43% specificity (AUC = 0.78), with an NPV of 89.29% and a PPV of 54.55%. The double-positive method provided superior accuracy, with a PPV of 91.67% and an NPV of 89.47%, demonstrating 73.33% sensitivity and 97.14% specificity. The double-negative method achieved 100% NPV and 100% sensitivity. Combining dd-cfDNA fraction and absolute quantification improves diagnostic accuracy for kidney transplant rejection, especially ABMR. The double-positive and double-negative approaches show high predictive value, offering potential clinical value for monitoring kidney transplant recipients.

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