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Abstract: FR-PO779

Wide Spectrum of Molecular Injury Highlights Heterogeneity of Banff Tubulitis and Interstitial Inflammation Lesions

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Allam, Sridhar Reddy, Medical City Fort Worth, Fort Worth, Texas, United States
  • Brennan, Daniel C., Johns Hopkins University, Baltimore, Maryland, United States
  • Maw, Thin Thin, University of Southern California, Los Angeles, California, United States
  • Stites, Erik, University of Colorado, Denver, Colorado, United States
  • Agrawal, Nikhil, CareDx Inc, Brisbane, California, United States
  • Shekhtman, Grigoriy, CareDx Inc, Brisbane, California, United States
  • Shihab, Fuad S., University of Utah Health, Salt Lake City, Utah, United States
Background

The pathological definition and clinical significance of borderline T cell-mediated rejection (BL-TCMR) remains active debate, leading to inconsistencies in therapeutic strategy. Previously published data suggests that donor-derived cell-free DNA (dd-cfDNA) levels at the time of BL-TCMR diagnosis may identify patients at risk of adverse long-term outcomes. We characterized dd-cfDNA levels associated with BL-TCMR among patients in the Kidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076).

Methods

Patients with BL-TCMR findings (Banff 2019) on either for-cause or surveillance biopsy and a dd-cfDNA result within 30 days were included in the analysis. Patients with biopsies showing isolated tubulitis or interstitial inflammation without tubulitis were also analyzed.

Results

We identified 56 cases of BL-TCMR with paired dd-cfDNA results; median dd-cfDNA among these patients was 0.34% (IQR:0.17 - 1.00) [Figure 1a]. The differences in dd-cfDNA among individual BL-TCMR combinations (t1/i1, t2/i1, t3/i1, t1/i2, t1/i3) were not significant, though the number of t3/i1 (n = 3, dd-cfDNA = 0.04%, 4.85%, 9.06%) and t1/i3 (n = 1, dd-cfDNA = 3.03%) cases was small. No differences were observed between biopsies with BL-TCMR and those with isolated tubulitis (t1/i0, t2/i0) or isolated inflammation without tubulitis (t0/i1) [Figure 1b]. 31 of 56 BL-TCMR cases had prior dd-cfDNA measurement, with median result of 0.24% (IQR: 0.20 - 0.37) obtained 63 (IQR: 53.5 - 100) days before the index biopsy. The median percent increase between these sequential results was 55% (IQR: -9 - 235%).

Conclusion

Substantial heterogeneity is observed with regards to dd-cfDNA levels at the time of BL-TCMR and the trajectory of dd-cfDNA preceding index biopsy. No differences in dd-cfDNA are observed between BL-TCMR and t/i lesions not presently included in Banff criteria for BL-TCMR. BL-TCMR, isolated tubulitis, and isolated inflammation without tubulitis represent a spectrum of molecular injury that may be further characterized via assessment of dd-cfDNA.

Funding

  • Commercial Support