Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Between 10% and 30% of renal transplant recipients (KTR) develop BK viremia; with 1-10% of KTR developing BK virus associated nephropathy (BKVAN), accounting for 7% of all renal allograft failures. Diagnosis currently requires biopsy confirmation with management using immunosuppression reduction having limited efficacy, often requiring re-biopsy to assess disease progression or resolution. Improved methods to diagnose BKVAN and follow disease progression or resolution are needed. We hypothesize that elevations (≥1%) of the level of donor derived cell free DNA (dd-cfDNA) may correlate with BKVAN, and potentially act as a surrogate to quantify the severity of viral injury for both diagnosis and management.
*Methods: We retrospectively analyzed the DART cohort of 384 KTR and 102 biopsies. BKV titers, biopsy results, and dd-cfDNA (AlloSure test) levels were correlated where available.
*Results: 11 patients with BK viremia had 14 paired dd-cfDNA and renal biopsy results, performed between 2015 and 2018. 7 KTR had BKV PCR titers that were correlated to dd-cfDNA results and biopsy pathology findings. Analysis showed a positive correlation of dd-cfDNA and BK viral load. Spearman correlation identified an r value = 0.874 (95% CI 0.35-0.98, p= 0.01). BK viremia without BKVAN had a median dd-cfDNA = 0.58% (IQR 0.43-1.15), while BKVAN had a median dd-cfDNA = 3.38% (IQR 2.3-4.56). KTR with biopsies meeting Banff criteria for acute cell-mediated rejection (TCMR; >Banff 1A) had a median BK PCR load = 4.42×105(IQR 2.1×103 – 5×105) while KTR not meeting criteria had median PCR load = 3.71×104 (IQR 1×105 – 2.2×107), these were not statistically different (p=0.45). Yet 5 of 7 BKVAN patients, but only 2 of 7 with isolated viremia, had biopsies meeting Banff criteria for TCMR, with median dd-cfDNA in non-rejection patients = 0.43% (IQR 0.29-0.91) versus 2.84% (IQR 1.49-4.29) in rejection patients, p=0.001.
*Conclusions: Lower levels of dd-cfDNA may indicate BK viremia is not causing nephropathy. In patients with BK viremia with or without BKVAN, the highest dd-cfDNA values tended to occur in patients whose biopsies met Banff criteria for TCMR. Further studies are required to define the role of dd-cfDNA in the diagnosis and or following the clinical response to treatment.
To cite this abstract in AMA style:Brennan D, Bromberg J, Yee J, Dholakia S, Haas M. Donor Derived Cell Free DNA (dd-cfDNA) May Aid in the Diagnosis of BK Virus Nephropathy [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-dd-cfdna-may-aid-in-the-diagnosis-of-bk-virus-nephropathy/. Accessed May 8, 2021.
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