Donor Derived Cell Free DNA Kinetics Post Kidney Transplant Biopsy

Abstract Background:Donor-derived cell-free DNA (dd-cfDNA) has generated interest as a biomarker for kidney transplant (KT) rejection. It is possible that the KT biopsy procedure can cause the release of dd-cfDNA, therefore affecting the reliability of this assay in the post biopsy period. In this study we evaluated the effect of KT biopsy on the kinetics of dd-cfDNA.Methods:We conducted a single arm prospective study. Samples were collected from 16 adult KT recipients undergoing KT biopsy. All participants had samples drawn within eight hours prior to the biopsy (pre-biopsy), within 20 minutes (hour 0), 2 hours (hour 2), and 24-48 hours (hours 24-48) after the biopsy. We evaluated the change in dd-cfDNA from the pre-biopsy time point to the following 3 time points after the biopsy.Results:At hour 0 and hour 2, there was a significantly larger log dd-cfDNA mean score compared to the pre-biopsy score [Least square mean (LSM) estimate 0.4 (0.17, 0.63) and 0.39 (0.09, 0.68) respectively]. By 24-28 hours post biopsy there was no significant difference in log dd-cfDNA mean score compared to the pre-biopsy score [LSM estimate -0.21 (-0.6, 0.19)]. Conclusion:KT biopsy leads to an increase in dd-cfDNA after the procedure, however, this rise is transient and resolves by 24-48 hour after the biopsy. Providers can obtain dd-cfDNA level as soon as 48 hours post biopsy with high confidence that the levels have not been affected by the biopsy. In addition, our findings suggest possible non-traditional reasons for increase in dd-cfDNA such as mechanical reasons.