Abstract: TH-PO0941
Diagnostic and Economic Analysis of Multibiomarker Kidney Rejection Rule-Out Tests
Session Information
- Transplantation: Clinical - Glomerular Diseases, Infections, and Rejection
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Singla, Akhil, Northwestern University, Evanston, Illinois, United States
- Chen, Kenny, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Robelly, Blade H, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Rebello, Christabel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Lantz, Connor, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Zhao, Lihui, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Lacombe, Ronnie, Eurofins Transplant Genomics, Lenexa, Kansas, United States
- Sinha, Rohita, Eurofins Transplant Genomics, Lenexa, Kansas, United States
- Hanna, Genevieve S, Eurofins Transplant Genomics, Lenexa, Kansas, United States
- Kleiboeker, Steven, Eurofins Transplant Genomics, Lenexa, Kansas, United States
- Park, Sookhyeon, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Mehrotra, Sanjay, Northwestern University, Evanston, Illinois, United States
- Friedewald, John J., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background
Recent biomarkers show good screening potential, but cost is a major impediment to frequent use. We evaluated the diagnostic and economic performance of the following biomarkers: Torque Teno Virus (TTV), Urine Chemokines CXCL9/CXCL10, and the combined Blood Gene Expression (GEP) and Cell-Free DNA (dd-cfDNA) test, costing $150, $200, and $5,993, respectively.
Methods
We analyzed CTOT-08 data from 226 kidney transplant recipients over two years post-transplant, comprising 462 biopsy-paired samples (121 subAR, 341 TX). We considered two-stage models (TSMs) with lower-cost tests used upfront to guide the use of more expensive combined GEP and dd-cfDNA test. Pareto frontier analysis was performed to maximize sensitivity and NPV while minimizing per-patient diagnostic costs (DC) for an optimal rule-out strategy. Multivariable logistic regression models (LRMs) were used for single-stage tests. Performance was validated in an independent cohort (136 recipients, 54 subAR, 92 TX).
Results
For DC between $2,000 and $4,000, a TSM using CXCL9 or CXCL9+CXCL10 LRM as stage 1 test, followed by a GEP+dd-cfDNA LRM upon stage-1 suspicion of subAR, showed maximum NPV (0.80-0.87) and sensitivity (0.40-0.64), with specificity and PPV of 0.72-0.89 and 0.48-0.57, respectively. For DC between $4,000 and $6,000, a CXCL10 test followed by a GEP+dd-cfDNA LRM showed the lowest NPV (0.80-0.85) and sensitivity (0.76-0.83) among all stage-1 models with TTV, CXCL9, CXCL10 alone, and their combination LRMs. In contrast, other TSMs, including TTV, then a GEP+dd-cfDNA LRM test, achieved maximum NPV (0.87-0.91) and sensitivity (0.71-0.87) while showing specificity and PPV of 0.48-0.7 and 0.37-0.45, respectively. The validation cohort didn’t show clear dominance.
Conclusion
Our study provides a framework for evaluating rule-out tests and shows that a two-stage approach reduces diagnostic costs while maintaining robust diagnostic performance.
Pareto frontier curves.
Funding
- NIDDK Support – Eurofins-Viracor