*Purpose: Donor-derived cell-free DNA (dd-cfDNA) has been proposed as a noninvasive biomarker to differentiate rejection from other types of injury in renal allografts.

*Methods: We analyzed all kidney transplant recipients who had for-cause dd-cfDNA testing at our institution since the test availability in September 2017 for evaluation of suboptimal renal function and clinical concern for rejection. We analyzed the association of dd-cfDNA results with clinical characteristics, biopsy diagnoses and pathological components of cellular rejection (ACR) and antibody mediated rejection (ABMR).

*Results: The median level of dd-cfDNA was 4.2% in patients with ABMR, 3.05% in those with mixed pathology of ABMR and ACR, 0.23% in those with ACR and 0.27% if no rejection (Fig 1). There was no association of dd-cfDNA with renal function (p=0.4). dd-cfDNA results improved the prediction of ABMR in patients with donor specific antibodies (DSA)(Fig 2) and levels of DSA’s did not strongly associate with dd-cfDNA levels (Fig 3). Levels of dd-cfDNA were associated with individual pathological components of ABMR diagnosis and microvascular inflammation but were less accurate than for composite ABMR. The levels of dd-cfDNA were higher (4.1% vs 0.27%, p=0.027) in patients with chronic-active ABMR (transplant glomerulopathy). There was no association between level of dd-cfDNA and presence of tubulitis (p=0.9) or interstitial inflammation (p=0.14).

*Conclusions: In patients with graft dysfunction, dd-cfDNA showed a significant association with ABMR and may predict its presence when DSA’s are present. No association with ACR was observed.

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