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Kidney Week

Abstract: PO2172

Trajectory of Gene Expression Profile and Donor-Derived Cell-Free DNA Before and After Subclinical Acute Rejection

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Park, Sookhyeon, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Dietch, Zachary, 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

Subclinical acute rejection (subAR) is associated with poor kidney allograft outcomes. Blood gene expression profile (GEP) and donor-derived cell-free DNA (dd-cfDNA) have been used to exclude or diagnose kidney allograft rejection non-invasively. However, the trajectory of GEP and dd-cfDNA are unknown after subAR. We investigated the changes in GEP and dd-cfDNA after subAR.

Methods

We analyzed 100 subjects with GEP and 87 with dd-cfDNA, with some subjects in both groups. GEP and dd-cfDNA were performed before, at, and after the time of subAR. The cohort was extracted from a previously reported prospective, multicenter observational study. GEP was performed using a microarray-based 120 gene expression profile. The study reported dd-cfDNA as a percentage of donor cell-free DNA over total cell-free DNA. Locally estimated scatterplot smoothing (LOESS) and linear mixed effect models were used to analyze longitudinal changes of GEP and dd-cfDNA scores.

Results

A total of 1,314 blood samples were assessed. The longitudinal changes of GEP scores at a sample level are shown in Figure 1. GEP scores peaked at the time of subAR and decreased after. The slope of GEP scores was significantly different after subAR (slope difference = -0.201 p-value <0.001) (Figure 2). On the other hand, dd-cfDNA continued to rise even after subAR (Figure 1). There were no significant changes to the slope of dd-cfDNA between pre-subAR and post subAR (0, p-value = 0.98)(Figure 2).

Conclusion

GEP scores significantly dropped, while dd-cfDNA persistently increased after subAR. How this may inform the biology of gene expression vs. dd-cfDNA after treatment of rejection requires additional study.

Funding

  • Commercial Support