Abstract: FR-OR080

Donor-Derived Cell-Free DNA Improves DSA-Informed Diagnosis of ABMR in Kidney Transplant Patients

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Jordan, Stanley C., Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Matas, Arthur J., University of Minnesota, Minneapolis, Minnesota, United States
  • Bunnapradist, Suphamai, UCLA, Los Angeles, California, United States
  • Langone, Anthony J., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Hiller, David, CareDx, Brisbane, California, United States
  • Woodward, Robert, CareDx, Brisbane, California, United States
  • Grskovic, Marica, CareDx, Brisbane, California, United States
  • Sninsky, John J, CareDx, Brisbane, California, United States
  • Yee, Jim, CareDx, Brisbane, California, United States
Background

Donor-derived cell-free DNA (dd-cfDNA) discriminates active T cell mediated (TCMR) and antibody mediated rejection (ABMR) in kidney transplant patients. Many transplant patients are monitored with donor-specific antibodies (DSA), which is a risk factor for ABMR. This study assesses the combined use of dd-cfDNA and DSA to diagnose active rejection and subtypes of rejection.

Methods

dd-cfDNA (AlloSure) was assayed in 107 blood samples with paired clinically indicated biopsies from 102 kidney transplant patients from the DART multicenter study (NCT02424227). Patients were divided into those who had prior or current positive DSA (DSA+, n=33 samples) and those who did not (DSA-, n=74 samples). DSA+ cutoffs were determined by center. Prevalence of biopsy-based diagnosis of rejection was computed. Mixed rejections were included in the ABMR group. Samples were further divided into dd-cfDNA > 1% (dd-cfDNA+) and dd-cfDNA ≤ 1% (dd-cfDNA-), and PPV of dd-cfDNA to predict ABMR and TCMR within DSA+ and DSA- patients were computed.

Results

DSA+ patients were 47 ± 14 years old, 48% Caucasian, and 58% male. DSA- patients were 53 ± 13 years old, 51% Caucasian, 62% male. 40% of DSA+ and no DSA- patients had ABMR. PPV of dd-cfDNA+ to detect ABMR in DSA+ patients is 76% (95% CI, 63%-100%). 14% of DSA+ and 13% of DSA- patients had TCMR. PPV of dd-cfDNA to detect TCMR in DSA+ patients is 25% (95% CI, 0%-54%) and in DSA- patients is 22% (95% CI 0%-44%). 13/16 DSA+, dd-cfDNA+ patients had ABMR and 1/16 had TCMR. 3/17 DSA+, dd-cfDNA- patients had ABMR and 3/17 had TCMR. 2/12 DSA-, dd-cfDNA+ patients had TCMR. 5/62 DSA-, dd-cfDNA- patients had TCMR.

Conclusion

Donor-derived cell free DNA may be used in conjunction with DSA status to improve the diagnosis of rejection in kidney transplant patients. Patients with dd-cfDNA+/ DSA+ have highest probability of rejection, most likely ABMR. Patients with dd-cfDNA-/DSA+ have a medium probability of rejection, either TCMR or ABMR. Since DSA is required to diagnose ABMR (Banff 2013), DSA- patients can only have TCMR. Patients with dd-cfDNA+/DSA- have a medium probability of TCMR and patients with dd-cfDNA-/DSA- have a low probability of TCMR.

Funding

  • Commercial Support