BK Virus Quantitative PCR

BK is a type of polyomavirus that is ubiquitous in nature and infects most people in early childhood. Seroprevalence is 60-100% in epidemiologic studies. Following primary infection, the virus becomes latent in lymphocytes and renal epithelium. Intermittent viral shedding may occur in immunocompetent individuals (up to 20% incidence) and more frequently in immunocompromised individuals (up to 60% incidence). BK is so-named from the initials of the patient from whom the virus was first isolated. A related poly-omavirus that infects humans is JC virus, which is associated with progressive multifocal leukoencephalpathy. 

BK virus reactivation is a major concern for renal transplant and bone marrow transplant recipients. Following reactivation, BK virus either clears spontaneously, perisists in urine, or progresses to viremia. Reactivation has been linked to tubulointerstitial nephritis and nephropathy as well as ureteral stenosis in renal transplant patients. Bone marrow transplant patients are at risk for hemorrhagic cystitis. BK virus associated nephropathy is an important cause of allograft failure and affects renal transplant patients an average of 44 weeks post-transplant. Increasing degrees of immunsuppression are associated with increased risk for BK reactivation. The risk for BKV nephropathy may be higher among HLA- and ABO-mismatched patients, possibly due to the increased rate of rejection and increased immunosuppression among such patients

BK virus infections progress through detectable stages. Patients with BK virus nephropathy most commonly present with an asymptomatic progressive rise in serum creatinine concentration. Urinalysis may reveal pyuria, hematuria, and/or cellular casts consisting of renal tubular cells and inflammatory cells Viral replication in urine is detected in up to 60% of renal transplant recipients and precedes viremia by approximately four weeks. Renal transplant recipients with higher urine DNA levels are more likely to develop detectable DNA in plasma. BK viremia is detected in 10 to 30 percent of recipients in the first six months post transplantation and in 5 to 10 percent of recipients thereafter. Sustained viremia precedes clinically overt BK virus nephropathy. 

Serum antibodies directed against BK virus are common in the general population and are not helpful in the diagnosis of BK virus infection. Quantitative real-time polymerase chain reaction (PCR) for BK viral DNA of plasma or serum, and less so of urine, is useful for diagnosis of BK virus infection and monitoring in transplant recipients. In the absence of a definitive renal biopsy, sustained BK viral load of more than 10,000 copies/mL for more than two weeks duration defines presumptive BK virus nephropathy. 

BK virus is a small nonenveloped double stranded DNA virus that codes for six viral proteins. T antigen is responsible for cell immortalization and latency. Agnoprotein assists in the assembly of viral particles. The three viral capsid proteins are named VP-1, VP-2, and VP-3.  PCR primers are directed to the large T antigen gene, which is a conserved sequence specific for BK virus. This assay does not detect JC virus or SV-40

Specimen requirement for PCR is 1mL of blood collected in a lavender top tube containing EDTA. 

References

Bechert CJ, et al. Monitoring of BK viral load in renal allograft recipients by real time PCR assays. Am J Clin Pathol. 2010;133(2):242-250.

Hirsch HH, Randhawa PS; AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation-guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13528.