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Abstract: TH-PO796

Next-Level Approach to Antibody-Mediated Rejection and T Cell-Mediated Rejection Diagnosis in Kidney Transplantation: Dynamic Duo of Urine CXCL10 and Donor-Derived Cell-Free DNA

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Fantus, Daniel, Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada
  • Casas, Sílvia, CareDx Inc, Brisbane, California, United States
  • Tangprasertchai, Narin S., CareDx Inc, Brisbane, California, United States
  • Viard, Thierry, CareDx Inc, Brisbane, California, United States
  • Belair, Justin, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada
  • Saw, Chee Loong, McGill University Health Centre, Montreal, Quebec, Canada
  • Daniel, Claude, McGill University Health Centre, Montreal, Quebec, Canada
  • Ho, Julie, University of Manitoba Max Rady College of Medicine, Winnipeg, Manitoba, Canada
Background

Biopsies are required to diagnose rejection but they are invasive and difficult to use for monitoring. While there is evidence that donor derived cell free DNA (dd-cfDNA) performs well as a biomarker of antibody-mediated rejection (AMR), its ability to identify T cell mediated rejection (TCMR) remains unclear. In contrast, urine CXCL10 is a well-characterised biomarker of tubulitis. Due to these complementary properties, we hypothesized that use of these 2 biomarkers together would improve the diagnosis of rejection phenotypes marked predominantly by tubulitis, particularly TCMR.

Methods

A single center exploratory study was conducted whereby 126 transplant biopsies (with paired plasma and urine) were selected. Banff criteria were followed to generate the following diagnostic categories: AMR (n=20), low and high grade TCMR (n=17) and normal histology (n=43). Urine CXCL10 was measured using the Meso Scale V-Plex assay. Cell free DNA was extracted from EDTA plasma samples and percent donor derived cell free DNA calculated using the CareDx AlloSeq cfDNA kit.

Results

The AUC for AMR (versus normal) was 0.952 (0.893-1000) using dd-cfDNA. In contrast, the AUC for AMR was 0.595 (0.469-0.722) using urine CXCL10 and increased to 0.969 (0.923-1.000) when dd-cfDNA was added (p=1.71X10-8). For high grade TCMR, AUC using dd-cfDNA was 0.762 (0.562-0.963). AUC using urine CXCL10 was 0.681 (0.474-0.888) and increased to 0.792 (0.585-1.000) when dd-cfDNA was added (p=0.16). For low grade TCMR, AUC was 0.577 (0.442-0.711) using dd-cfDNA. AUC was 0.595 (0.424-0.767) using urine CXCL10 and increased to 0.652 (0.473-0.832) (p=0.32) when dd-cfDNA was added.

Conclusion

Urine CXCL10 is a weaker diagnostic biomarker of AMR compared to dd-cfDNA. In contrast, when evaluating TCMR, there was no clear advantage of one biomarker over the other, though their combination may improve diagnosis. These findings require prospective multi-center studies.

Funding

  • Private Foundation Support