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Abstract: PO2043

Three Distinct Phases in the Amount of Total and Donor-Derived Cell-Free DNA Are Observed over Time in Plasma from Kidney Transplant Recipients

Session Information

Category: Transplantation

  • 1901 Transplantation: Basic

Authors

  • Van Hummelen, Paul, Natera, Inc., San Carlos, California, United States
  • Lee, Soong, Natera, Inc., San Carlos, California, United States
  • Ahmed, Ebad, Natera, Inc., San Carlos, California, United States
  • Gauthier, Philippe, Natera, Inc., San Carlos, California, United States
  • Tabriziani, Hossein, Natera, Inc., San Carlos, California, United States
  • Zimmermann, Bernhard, Natera, Inc., San Carlos, California, United States
  • Billings, Paul Richard, Natera, Inc., San Carlos, California, United States
  • Swenerton, Ryan, Natera, Inc., San Carlos, California, United States
Background

Donor-derived cell-free DNA (dd-cfDNA) is a clinically validated biomarker for allograft rejection in kidney transplant (KT) recipients. Fluctuations in the total amount of cfDNA (including donor and recipient-derived cfDNA) can impact the reported dd-cfDNA fraction. Here we analyzed the changes in total and dd-cfDNA quantity, over time, in KT patients.

Methods

We selected 3,925 samples from 747 clinically stable patients with >3 longitudinal samples. The median time from KT to sample collection was 134 days (range: 1 day - 37 years). Total cfDNA and dd-cfDNA were measured using the ProsperaTM test and expressed as relative units per ml plasma (RU/ml). Dynamic changes in dd-cfDNA and total cfDNA over time were compared to their respective medians for all samples at 3-year post-KT, defined as reference.

Results

One week following KT, median quantities of total cfDNA were elevated ~2-fold above the reference value (494 RU/ml), which normalized over the first month. At month 3, a 1.6-fold increase was observed, which normalized to the reference value over the first year post-KT. In contrast, the absolute quantity of dd-cfDNA was initially elevated ~100-fold above the reference (1.06 RU/ml) post-KT, which normalized over the first month to the reference level where it remained stable. The elevation in dd-cfDNA during the first week is likely due to trauma to the donor organ from surgery. Additionally, a significant elevation in both total and dd-cfDNA was observed in patients who received a kidney from a deceased donor as compared to a living donor.

Conclusion

Total and dd-cfDNA levels were highly dynamic in the first year post-KT but stabilized afterwards. Further investigation is needed to determine the causes of total-cfDNA increases at months 3 and 4. Potential factors include inflammatory responses and NETosis, viral infection or transient interstitial fibrosis and tubular atrophy (IF/TA) in the donor organ. The time dependent dynamics were statistically significant, but with a high coefficient of variance (CV>50%), which limits extrapolations to individual patients. Potential variability should be considered when interpreting dd-cfDNA tests performed within the first week post-KT.