Abstract: FR-PO805
Correlation of Donor-Derived Cell-Free DNA With Histology and Molecular Diagnoses of T-Cell Mediated Rejection in Kidney Transplant Biopsies
Session Information
- Transplantation: Clinical - Biomarkers
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Kumar, Dhiren, Virginia Commonwealth University Health System, Richmond, Virginia, United States
- Moinuddin, Irfan Ahmed, Virginia Commonwealth University Health System, Richmond, Virginia, United States
- Kamal, Layla, Virginia Commonwealth University Health System, Richmond, Virginia, United States
- Christensen, Johanna L., Virginia Commonwealth University Health System, Richmond, Virginia, United States
- Shinbashi, Meagan, Virginia Commonwealth University Health System, Richmond, Virginia, United States
- Raju, Nihar G., Virginia Commonwealth University Health System, Richmond, Virginia, United States
- Minniti, Robert Joseph, Virginia Commonwealth University Health System, Richmond, Virginia, United States
- Halloran, Philip F., University of Alberta, Edmonton, Alberta, Canada
- Gupta, Gaurav, Virginia Commonwealth University Health System, Richmond, Virginia, United States
Background
We reported correlation of donor-derived cell-free DNA (dd-cfDNA) with histologic and molecular diagnosis (MMDx) of kidney transplant biopsies (Gupta et al, Transplantation 2021). Here we build on that initial cohort with a larger TCMR sample size and provide data on therapy and outcomes.
Methods
We identified biopsies classified as TCMR by histology and/or MMDx. Those with viral/bacterial nephritis/mixed rejection were excluded. Prior to therapy fractional dd-cfDNA (%; Allosure) was measured. 37 such biopsies were divided into two groups, H+M+ (concomitant TCMR; N=18) and H+M- (discordant TCMR; N=19).
Results
Median dd-cfDNA was lower (p=0.02) in H+M- (0.32%; IQR: 0.15-0.43) compared to H+M+ group (1.03%; IQR: 0.38-1.8). In histologic findings interstitial and tubular inflammation (i+t) (4.8±1.5 vs 3.3±1.2, p=0.002) was worse for H+M+ vs H+M-. A graded dose-response was seen between i+t and dd-cfDNA for H+M+ and not seen in H+M- (Figure 1a). Borderline/1A TCMR was seen frequently in the H+M- (16/19, 84%) while TCMR ≥1B was seen in the H+M+ group (12/18, 67%). MMDx scores for TCMR (0.50±0.29 vs 0.02±0.02, p<0.0001) and inflammation (4.6±2.1 vs -0.55±1.5, p<0.0001) were higher in the H+M+ vs H+M- group. eGFR at biopsy was worse in the H+M+ group (27±19ml/min) compared to the H+M- (40±23ml/min; p=0.06). A majority of H+M+ were treated (16/18; 89%; 14 rATG and 2 steroids only) and a minority of H+M- received steroids only (7/19; 37%). Despite this discrepancy, there was improvement in eGFR in both groups. At median follow-up of 14.7 months eGFR improved to 34±24ml/min in the H+M+ and 49.2±26ml/min in the H+M- group (Figure 1b). All 4 graft losses and one patient death was in the H+M+ group (p=0.02).
Conclusion
We confirm our findings in patients with histologic TCMR absent on molecular gene expression is associated with low dd-cfDNA. Majority of patients had improvement in kidney function without targeted therapy. This may indicate low-grade TCMR is a ‘response to wounding’, rather than cognate allo-recognition.