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Abstract: FR-PO786

Serial Testing of Blood Gene Expression and Donor-Derived Cell-Free DNA for Predicting Future Kidney Allograft Failure

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Guo, Kexin, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Kushner, Alexis J., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Rebello, Christabel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Kinsella, Bradley M., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Sinha, Rohita, Eurofin Viracor, Lee Summit, Missouri, United States
  • Zhao, Lihui, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Friedewald, John J., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Park, Sookhyeon, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background

Both gene expression profiles (GEP) and donor-derived cell-free DNA (dd-cfDNA) have been established as non-invasive biomarkers to detect subclinical and clinical acute rejection in a kidney allograft. However, the clinical impact of combined serial testing of GEP and dd-cfDNA on kidney allograft survival has not been well studied. We hypothesized that we could predict future kidney allograft survival using serial testing of combined GEP and dd-cfDNA.

Methods

We analyzed 261 subjects from a previously reported multicenter, prospective observational study. Multiple serial samples of GEP and dd-cfDNA were collected throughout the study period. Graft failure was defined as returning to dialysis or re-transplant. We used a joint model to predict future allograft survival using serial GEP and dd-cfDNA and allograft failure. The study cohort was randomly divided into 70 and 30%, training and testing sets, respectively. We assessed the model performance with the area under the receiver operating characteristic (AUROC).

Results

Of 261 subjects, 182 (70%) were used for training the model. A total of 16 cases of allograft failure were observed in the training set. In the training set, the AUROC to predict graft failure at 4-year post kidney transplant (KT) was 0.83 using GEP and dd-cfDNA until 1 year KT (Fig 1A). When we used GEP and dd-cfDNA data from up to 2 years post KT, the AUROC improved to 0.88 (Figure 1B). For the validation set, 7 graft failures were observed from 79 subjects. The performance remains stable in the validation set. The AUROCs were 0.67 and 0.83, using up to 1-year and 2-year serial GEP and dd-cfDNA data, respectively.

Conclusion

The combination of GEP and dd-cfDNA tests can be used to predict future graft failure.

Funding

  • Private Foundation Support