Abstract: PO2180
Can a Combination of Blood Gene Expression and Donor-Derived Cell-Free DNA Improve Detection of Acute Rejection in Stable and Unstable Kidney Allograft Recipients?
Session Information
- Transplantation: Clinical - Noninvasive Biomarkers, Immune Regulation, and Fascinomas
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1902 Transplantation: Clinical
Authors
- Park, Sookhyeon, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Guo, Kexin, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Zhao, Lihui, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Friedewald, John J., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background
Non-invasive biomarkers for the detection of acute clinical rejection or subclinical acute rejection (subAR) have shown modest diagnostic performance. Therefore, we hypothesized that a combination of gene expression profile (GEP) and donor-derived cell-free DNA (dd-cfDNA) would improve the diagnostic performance.
Methods
We analyzed 559 blood samples paired with kidney biopsies from CTOT-08 study. GEP probability scores were analyzed as both binary and continuous variables. GEP probability scores >50 were considered positive. dd-cfDNA results > 0.7 % were considered as positive for binary analysis. We calculated the area under the receiver operating characteristics (AUROC) for each test and the combination of both tests. We conducted a logistic regression to assess the performance of combined GEP and dd-cfDNA scores as continuous variables.
Results
153 rejections consisted of 50 clinical and 103 subclinical rejection cases. Among 406 non-rejection cases, 81 cases had an acute elevation of creatinine, and 325 cases had stable kidney function.
For binary analysis, dd-cfDNA showed better positive predictive value (PPV, 0.58, 95% CI 0.48-0.67) than GEP alone (0.49, 95% CI 0.41-0.58). When both tests were positive, PPV went up to 0.75 (95% CI, 0.61-0.88). GEP (0.82, 95% CI 0.78-0.86) and dd-cfDNA alone (0.81, 95% CI 0.77-0.85) had similar NPV. The NPV improved to 0.88 (95% CI, 0.84-0.92) when both assays were negative (Table 1). The logistic regression combining both continuous assay scores achieved an AUROC of 0.80 significantly higher than 0.75 (GEP alone, p-value <0.001) and 0.72 (dd-cfDNA alone, p-value <0.01).
Conclusion
Combining the GEP and dd-cfDNA can improve the ability to distinguish acute rejection in both stable and unstable patients.
Funding
- Commercial Support –