Purpose: Donor-derived cell-free DNA (dd-cfDNA) is an established marker of active rejection in de novo kidney transplant recipients. Here we characterize dd-cfDNA in patients who have received a repeat transplant since both prior and newly transplanted kidneys may be sources of dd-cfDNA found in the recipient's bloodstream. Methods: The DART study included 41 patients with more than one renal allograft in situ. Patients from the multiple transplant group who began dd-cfDNA surveillance testing (AlloSure) within 2 months post-transplant and had no rejections (n=15) and those who met the same conditions but had single kidney transplant (n=204) were included in the surveillance groups. A cohort with clinically indicated biopsy of the most recent allograft was examined for the impact of biopsy-proven active rejection on dd-cfDNA in repeat transplant patients. dd-cfDNA was measured by targeted amplification and sequencing as described previously. The assumptions in the computation of dd-cfDNA level are not impacted by the number of allografts, but do not distinguish which kidney(s) may have contributed dd-cfDNA. Results: 71 samples from the multiple transplant surveillance group had a median dd-cfDNA of 0.30% (interquartile range (IQR) 0.11%, 0.72%). 204 patients (1164 samples) with single allograft and no rejection had a significantly lower median dd-cfDNA of 0.19% (IQR 0.1%, 0.35%, p < 0.001). The demographics of the multiple and single allograft patients were similar. In 8 retransplanted patients with a diagnosis of active rejection of the most recent allograft, the median dd-cfDNA at the time of a clinically indicated biopsy was 2.06%, significantly higher than the median 0.45% (p=0.005) of 6 retransplanted patients negative for rejection at a clinically-indicated biopsy. Patients with single allograft and active rejection had a median dd-cfDNA of 1.6%, and patients with no biopsy findings of rejection had a median of 0.3%. Conclusions: Patients with multiple kidney transplants in situ have higher combined dd-cfDNA levels than patients with a single allograft. However, the dd-cfDNA levels during periods of stability are still relatively low compared to levels found in biopsy proven rejection. dd-cfDNA testing has the potential to be used to monitor active rejection and related injury in patients with repeat kidney transplants.

CITATION INFORMATION: Mehta S., Chang J., Hailey T., Hiller D., Grskovic M., Yee J., Mannon R. Repeat Kidney Transplant Patients with Active Rejection Have Elevated Donor-Derived Cell-Free DNA Am J Transplant. 2017;17 (suppl 3).

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