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Abstract: TH-OR56

The Role of Combined Gene Expression Profiling and Donor-Derived Cell-Free DNA to Diagnose Acute Rejection in Patients with Acute Allograft Dysfunction

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Park, Sookhyeon, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Guo, Kexin, Northwestern University Feinberg School of Medicine, Chicago, Illinois, 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
Background

Gene expression profiling (GEP) has been used to monitor for subclinical acute rejection. Conversely, the majority of data with donor-derived cell-free DNA (dd-cfDNA) has been in patients with allograft dysfunction. We hypothesized that combining GEP and dd-cfDNA could improve the diagnostic performance to detect acute rejection in patients with acute allograft dysfunction.

Methods

We analyzed a total of 131 blood samples paired with kidney biopsies from patients (n=96) with ‘for cause’ biopsies in the CTOT 08 study. Blood samples were analyzed with the GEP and the dd-cfDNA assay. The area under the receiver operating characteristics (AUROC) was used for GEP and dd-cfDNA separately based on their continuous output variables, and for combining two assays with logistic regression.

Results

Of 131 blood samples, 50 and 81 cases were biopsy-proven clinical acute rejection and acute allograft dysfunction without rejection, respectively. In binary analysis, GEP showed a lower positive predictive value (PPV) at 0.54 to 0.64 from dd-cfDNA, but a higher negative predictive value (NPV) at 0.80 to 0.70. When both tests were positive, PPV increased to 0.68 (95% CI, 0.50-0.88). In cases when both tests were negative, NPV increased to 0.88 (95% CI< 0.78-0.96) (Table 1). Performance of GEP and dd-cfDNA on detection of antibody-mediated rejection and acute cellular rejection shown in Figure 1. The combined use of two assays showed similar AUROC, to 0.75 than GEP (0.74, p-value = 0.26) and dd-cfDNA (0.72, p-value=0.69).

Conclusion

Combined GEP and dd-cfDNA assay might improve the diagnostic performance of acute rejection in patients with acute renal allograft dysfunction.

Funding

  • Commercial Support