Significant inter-assay variability in the quantification of BK virus (BKV) DNA has limited the broad applicability of thresholds for the management of BKV infection in transplantation. In 2016, the 1^st World Health Organization (WHO) International Standard for BKV (primary standard) was introduced as a common calibrator to improve the harmonization of BKV nucleic acid amplification testing (NAAT) and allow comparison of biological measurements worldwide. We evaluated the impact of the calibration of BKV NAAT results to the International Unit (IU) using the Altona RealStar® BKV assay (Altona) and the Exact Diagnostics® BKV Verification Panel, a secondary standard traceable to the primary standard. Comparison of the primary and secondary standards on Altona revealed nearly identical linear regression equations (primary standard, Y = 1.048*X – 0.2833, R²=0.986; secondary standard, Y = 1.039*X – 0.2551, R²=0.986) and conversion factors (primary standard, 1.11 IU/copy; secondary standard 1.09 IU/copy). Comparison of Altona with our laboratory-developed BKV NAAT assay in IU/mL versus copies/mL using Passing-Bablock regression, revealed similar regression lines, no proportional bias, and improvement in the systematic bias (95% confidence interval of intercepts, copies/mL, -0.52 to -1.01; IU/mL, 0.07 to -0.36). Additionally, Bland-Altman analyses revealed a clinically significant reduction of bias when results were reported in IU/mL (IU/mL, -0.099 log₁₀; copies/mL, -0.697 log₁₀). These results indicate that use of a common calibrator improved the agreement between the two assays. As clinical laboratories worldwide use calibrators traceable to the primary standard to harmonize BKV NAAT results, we can anticipate improved inter-assay comparisons and potential for establishing broadly applicable quantitative BKV DNA load cutoffs in IU/mL for clinical practice. Additionally, clinicians managing BKV infection in immunocompromised patients will need to understand the local impact of results interpretation as BKV NAAT results are reported in IU/mL.

CITATION INFORMATION: Tan S, Milligan S, Sahoo M, Taylor N, Pinsky B. Calibration of BK Virus Nucleic Acid Amplification Testing to the 1^st WHO International Standard for BK Virus. Am J Transplant. 2017;17 (suppl 3).

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