Specimen Required

Plasma

Container/Tube: Lavender-top (EDTA).

Specimen Volume: 1 mL of plasma

Collection Instructions: Spin specimen down promptly and separate plasma from EDTA tube.

Specimen Minimum Volume

0.5 mL

Transport Temperature

*The samples should be stored for not more than 2 days at 2-8^°C.

**For longer delay, freeze at -20^°C or below and transport on dry ice.

Reject Due To

Useful For

Quantitative detection of BK viremia in plasma of renal transplant recipients to monitor BK virus induced nephritis.

Clinical Information

BK virus (a human polyomavirus) is a nonenveloped icoashedral virion containing a circular dsDNA genome. Primary BKV infection is typically asymptomatic or associated with a mild upper respiratory disease. By age nine 98% of children have evidence of previous exposure. The virus persists in the kidney and B lymphocytes following primary infection. Infection is lifelong and associated with asymptomatic shedding in the urine (1% detected by polymerase chain reaction in urine from healthy subjects). Significant illness results from reactivation of latent virus from the kidneys in immunocompromised patients; including pregnancy, organ transplant recipients, antitumor therapy recipients, AIDS and other immunodeficient states.

BKV nephropathy (BKVN) has increasingly been recognized as an early event and occurs within the first year after transplantation. Patients usually remain asymptomatic and are detected when they experience renal insuffiency. BKV DNA is detected in the urine and plasma in nearly all cases of BKVN. Renal dysfunction secondary to ureteric stricture leading to hydronephrosis is occasionally seen and severe systemic disease leading to multiorgan failure has been reported.

Definitive BKVN diagnosis requires renal biopsy showing polyomavirus-induced cytopathic changes in tubular or glomerular epithelial cells. Because BKVN can be focal in distribution, a negative biopsy result does not rule out BKVN with certainty. BKV DNA can be detected in urine and plasma by PCR. Because of the high rate of excretion of BKV in urine of renal transplant recipients, the finding of BKV DNA by PCR in urine is of limited use. Testing of BKV DNA in plasma is more promising as a noninvasive diagnostic test for BKVN. BKV DNA quantitation in plasma is used as an important diagnostic tool and is detected in 15 – 30% of renal transplant recipients during the first post-transplantation year. Quantitative PCR for BKV in plasma has a high degree of sensitivity and specificity, however not all patients with BKV viremia have nephritis. Higher BKV DNA copy number is associated with an increased likelihood of having nephritis and has been correlated with severity of disease. BKV DNA >10,000 copies/ml plasma is used by some as a threshold for significant infection and correlates with BKVN. BKVN, however, can be seen with BKV DNA at <7,000 copies/ml plasma.

Screening for quantitative BKV DNA in plasma at 1, 3, 6, 12, and 24 months has been shown to be effective in detecting early infection before the occurrence of nephritis.

Interpretation

BKV DNA >10,000 copies/ml plasma is used by some as a threshold for significant infection and correlates with BKVN. BKVN, however, can be seen with BKV DNA at lower levels.

References

Major, E. O., Ryschkewitsch, C., Valsamakis, A., and Hou, J. 2007. Human Polyomaviruses, p. 1612-1621. In Murray, P. R., Baron, E. J., Jorgensen, J. H., Landry, M. L., and Pfaller, M. A. Manual of Clinical Microbiology, 9^th ed., vol. 2. ASM Press, American Society for Microbiology, Washington, DC.

Medipalli, R, Vasudev B, Zhu Y, et al. 2007. Improved outcomes of BKVN: Impact on [BK virus surveillance protocol. Am J Transplant 7[Suppl 2]: 150.

Tan, C. S., and Koralnik, I. J. 2010. JC, BK, and Other Polyomaviruses: Progressive Multifocal Leukoencephalopathy, p. 2051-2058. In Mandell, D., Bennett, J. E., and Dolin, R. 2010. Principles and practice of infectious diseases, 7^th ed., vol. 2. Churchill Livingstone, Elsevier, Philadelphia, PA.

Method Description

Quantitative real-time PCR

Performing Laboratory Location

National Microbiology Laboratory, Winnipeg, MB