*Purpose: BK virus reactivation is common among kidney transplant recipients (KTRs) and is a risk factor for allograft loss. Currently, there is no clearly established threshold for BK quantification that predicts BK virus-associated nephropathy (BKVN). While management focuses on strategic reduction of immunosuppression, it is challenging to differentiate between BK viremia (BKV), BKVN or acute rejection in this setting. Here we demonstrate the relationship between dd-cfDNA as a marker of allograft injury and clinical outcomes in KTRs with BKV.

*Methods: Electronic medical records were reviewed to identify KTRs who developed BKV from January 2020 to January 2022 and were monitored with dd-cfDNA (AlloSure, CareDx). dd-cfDNA was collected as part of standard of care assessment for post-transplant surveillance. Peak BK viral titers and allograft biopsies were paired with dd-cfDNA results within 30 days for the purpose of this study.

*Results: A total of 33 patients were identified for analysis. Patient demographics are summarized in Table 1. Median time from transplant to peak BK viral titers was 6 months. There was no significant correlation between BK viral titer and dd-cfDNA levels (Figure 1). The median dd-cfDNA level for patients with BKV was 0.24% (IQR 0.17%-0.37%) compared to 0.62% (IQR 0.26%-2.5%) for BKVN (Figure 2, p=0.14). The median dd-cfDNA for acute rejection (acute cellular rejection or mixed) was 0.72% (IQR 0.5%-4.3%), which was significantly higher than patients with no histological evidence of rejection (Figure 2, p=0.03). Of those patients with dd-cfDNA >0.5% at the time of peak BK titers, 3 (30%) developed ACR within 60 days, compared to 1 patient (4%) with dd-cfDNA <0.5% who developed ACR following BK clearance.

*Conclusions: Elevated dd-cfDNA levels in the setting of BK viremia is associated with acute rejection. Furthermore, dd-cfDNA levels >0.5% may identify patients that are at increased risk of developing future rejection episodes. dd-cfDNA may be useful in assessing the clinical course of BKV and BKVN and provide additional information to interpretation of viral titers.

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