Kidney Week

Abstract: FR-PO1196

Progressive Subthreshold Donor-Derived Cell-Free DNA Rise as a Marker of Alloimmunogenic Kidney Allograft Injury

Session Information

• Transplantation: Clinical - Rejection, Biomarkers, and Pharmacology
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2002 Transplantation: Clinical

Authors

• Ahmed, Ahmed Khalafalla Mohamed, University of Illinois Chicago, Chicago, Illinois, United States

Ahmed Khalafalla Mohamed Ahmed, MD, MS

• Sanoufa, Mazen, University of Illinois Chicago, Chicago, Illinois, United States

Mazen Sanoufa, MD

• Miqdad, Mohammed A., University of Illinois Chicago, Chicago, Illinois, United States

Mohammed A. Miqdad, MD, MBBS

• Dabbas, Walaa, University of Illinois Chicago, Chicago, Illinois, United States

Walaa Dabbas, MD

• Naik, Ruchi Harshadrai, University of Illinois Chicago, Chicago, Illinois, United States

Ruchi Harshadrai Naik, MD, PhD

• Gallon, Lorenzo G., University of Illinois Chicago, Chicago, Illinois, United States

Lorenzo G. Gallon, MD

• Hajjiri, Zahraa, University of Illinois Chicago, Chicago, Illinois, United States

Zahraa Hajjiri, MD

Background

Donor-derived cell-free DNA (dd-cfDNA) is a biomarker of kidney allograft injury, with values ≥1% associated with rejection risk. We evaluated whether progressive subthreshold dd-cfDNA rises (<1%) are associated with alloimmunogenic tissue injury.

Methods

We retrospectively analyzed 68 kidney transplant recipients with clinically indicated allograft biopsy and at least 3 consecutive dd-cfDNA measurements <1% within 6 months prior to biopsy. Progressive dd-cfDNA rise was defined as ≥2 consecutive increases of ≥10%, ≥20%, or ≥30%. Allo-immunogenic injury included ACR, AMR, borderline rejection, and probable AMR. Diagnostic performance was assessed via ROC analysis, sensitivity, specificity, PPV, NPV, and accuracy.

Results

27 (39.7%) had biopsy-proven rejection. Median time from transplantation to biopsy was 12 months (IQR 9–22.8). For rejection, increasing dd-cfDNA rise thresholds improved specificity and PPV but lowered sensitivity. A 10% rise showed sensitivity of 48.2% (95% CI 28.7–68.1) and specificity of 63.4% (46.9–77.9), whereas a 30% rise increased specificity to 92.7% (80.1–98.5) and PPV to 72.7% (43.7–90.2), with sensitivity decreasing to 29.6% (13.8–50.2). For allo-immunogenic injury, specificity increased from 67.7% (48.6–83.3) at the 10% threshold to 100% (88.8–100) at the 30% threshold, with PPV also reaching 100% (71.5–100).
ROC analysis showed modest but improved discrimination with increasing thresholds. AUC values for biopsy-proven rejection were 0.56 (95% CI 0.44–0.68), 0.63 (0.52–0.74), and 0.61 (0.52–0.71) for 10%, 20%, and 30% thresholds, respectively. For allo-immunogenic injury, AUC increased from 0.58 (0.47–0.70) to 0.65 (0.57–0.72).

Conclusion

Progressive subthreshold dd-cfDNA rise may identify clinically significant allo-immunogenic injury despite low absolute dd-cfDNA values. Higher relative rise thresholds improved specificity and PPV, supporting dd-cfDNA trajectory as a potential adjunct marker for immune-mediated allograft injury.