TY - JOUR
T1 - Donor-derived Cell-free DNA and the Prediction of BK Virus-associated Nephropathy
AU - Kant, Sam
AU - Bromberg, Jonathan
AU - Haas, Mark
AU - Brennan, Daniel
N1 - Publisher Copyright:
© 2020 Wolters Kluwer Health. All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background. Approximately 15% of kidney transplant recipients (KTRs) develop BK viremia (BKV), with 1%-10% developing BK virus-associated nephropathy (BKVAN), which histologically resembles rejection. The Diagnosing Acute Rejection in Kidney Transplant Recipients (DART) study showed that donor-derived cell-free DNA (dd-cfDNA) levels <1% have a negative predictive value of 85% for active allograft rejection. Using data from this study, we evaluated the association of dd-cfDNA with plasma BK viral loads and biopsy findings to determine if dd-cfDNA can distinguish asymptomatic BKV from BKVAN. Methods. Data on dd-cfDNA, plasma BK viral loads, and biopsy findings from patients from the DART study were retrospectively examined. BKV was defined as 500-10 000 copies/mL. Presumptive BKVAN was defined as BK >10 000 copies/mL. Results. Of 102 participants with biopsies, 10 patients with BKV and BKVAN had paired dd-cfDNA, and viral loads available for analysis. Patients diagnosed with BKV and BKVAN had a median dd-cfDNA of 0.58% (IQR 0.43-1.15) and 3.38% (IQR 2.3-4.56, P = 0.001), respectively. dd-cfDNA titers correlated with BK PCR viral loads (R = 0.874, P = 0.01) and the presence of histologic evidence of BKVAN (100% sensitivity, 50% specificity). Five of 7 patients with BKVAN, but only 2 of 7 with BKV, had biopsies meeting Banff criteria for T-cell-mediated rejection. Median dd-cfDNA in nonrejection patients was 0.43% versus 2.84% in rejection patients (P = 0.001). Conclusion. Higher dd-cfDNA titers were associated with higher BK viral loads, biopsy-diagnosed BVAN, as well histologic changes meeting Banff criteria for as T-cell-mediated rejection. dd-cfDNA may be a useful noninvasive test to assess for progression of BKV to BKVAN.
AB - Background. Approximately 15% of kidney transplant recipients (KTRs) develop BK viremia (BKV), with 1%-10% developing BK virus-associated nephropathy (BKVAN), which histologically resembles rejection. The Diagnosing Acute Rejection in Kidney Transplant Recipients (DART) study showed that donor-derived cell-free DNA (dd-cfDNA) levels <1% have a negative predictive value of 85% for active allograft rejection. Using data from this study, we evaluated the association of dd-cfDNA with plasma BK viral loads and biopsy findings to determine if dd-cfDNA can distinguish asymptomatic BKV from BKVAN. Methods. Data on dd-cfDNA, plasma BK viral loads, and biopsy findings from patients from the DART study were retrospectively examined. BKV was defined as 500-10 000 copies/mL. Presumptive BKVAN was defined as BK >10 000 copies/mL. Results. Of 102 participants with biopsies, 10 patients with BKV and BKVAN had paired dd-cfDNA, and viral loads available for analysis. Patients diagnosed with BKV and BKVAN had a median dd-cfDNA of 0.58% (IQR 0.43-1.15) and 3.38% (IQR 2.3-4.56, P = 0.001), respectively. dd-cfDNA titers correlated with BK PCR viral loads (R = 0.874, P = 0.01) and the presence of histologic evidence of BKVAN (100% sensitivity, 50% specificity). Five of 7 patients with BKVAN, but only 2 of 7 with BKV, had biopsies meeting Banff criteria for T-cell-mediated rejection. Median dd-cfDNA in nonrejection patients was 0.43% versus 2.84% in rejection patients (P = 0.001). Conclusion. Higher dd-cfDNA titers were associated with higher BK viral loads, biopsy-diagnosed BVAN, as well histologic changes meeting Banff criteria for as T-cell-mediated rejection. dd-cfDNA may be a useful noninvasive test to assess for progression of BKV to BKVAN.
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U2 - 10.1097/TXD.0000000000001061
DO - 10.1097/TXD.0000000000001061
M3 - Article
C2 - 33134498
AN - SCOPUS:85095790048
SN - 2373-8731
JO - Transplantation Direct
JF - Transplantation Direct
M1 - e622
ER -