BK Virus

Diagnosis

Indications for Testing

  • Renal transplant patient with deterioration in renal function; transplant patient presenting with hemorrhagic cystitis

Laboratory Testing

  • PCR assay
    • Quantitative and qualitative testing available
    • Substantially more sensitive than urine cytology measurements
    • Quantitative testing
      • Provides objective estimate of viral load
      • Can distinguish BK from JC viruria
  • Urine cytology
    • Infected cells show rounded nuclei with intranuclear basophilic inclusion on Pap stain bodies (decoy cells)
      • Lack of decoy cells suggests no viral nephropathy
      • Positive decoy means reactivation of virus but does not necessarily mean infection (100% sensitive but only 20% positive predictive value)

Histology

  • Gold standard in BK virus allograft nephropathy is renal biopsy
    • Demonstration of BK virus inclusions in tubular epithelium in renal tissue
  • Immunohistochemistry – simian virus 40 (SV-40); also known as BK virus

Differential Diagnosis

  • Other viral infections – cytomegalovirus
  • Acute or chronic rejection
  • Malignancy

Monitoring

  • PCR quantitative – expect reduction in viremia with treatment
  • International consensus panel (Hirsch HH, 2005) – monitoring for BK virus every 3 months for the first 2 years post-renal transplant or when allograft dysfunction occurs
    • Use urine cytology screen or urine PCR

Clinical Background

BK virus is a polyoma virus in the same family of viruses as human papilloma and JC virus and has become recognized as an important causal infectious agent in complications after kidney transplant.

Epidemiology

  • Prevalence
    • Primary BK infection generally occurs in childhood without specific symptoms
      • 90% of population seropositive
    • 1-5% of kidney transplant patients are affected
  • Transmission
    • Presumably transmitted via respiratory droplets
    • Other speculated modes include urine, semen, blood transfusion and organ transplantation

Organism

  • Double-stranded DNA virus
  • Human papillomavirus (genetically similar to JC virus)
  • After primary infection, BK virus becomes latent in the kidneys and urinary tract
  • Reactivated BK virus infection occurs with immunosuppression

Clinical Presentation

  • Clinical disease is rare in immunocompetent adults
  • BK virus infections are a cause of morbidity and mortality for patients with hematologic malignancies and transplants (most often bone and kidney)
  • Illnesses caused by BK virus
    • Nephropathy and graft loss in renal transplant patients
      • BK virus allograft nephropathy (BKVAN) present in up to 8% of kidney transplant patients
        • Tubulointerstitial nephritis
          • Most common manifestation
          • Leads to irreversible graft failure in 40-50% of patients
        • New immunosuppressive regimens may increase the risk of BKVAN
    • Hemorrhagic cystitis and renal impairment in patients with hematologic malignancy and bone marrow transplant

Treatment

  • Bone marrow/hematologic malignancies
    • Supportive in hemorrhagic cystitis; most patients recover
    • Refractory cystitis may be catastrophic
      • Poor response to antiviral therapy
  • Renal transplant patients
    • If no active rejection present, judicious reduction of immune suppression is acceptable and usually decreases viral load

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
BK Virus, Quantitative PCR 0090067
Method: Quantitative Real-Time Polymerase Chain Reaction

Exclude diagnosis of BKVAN

Monitor patient response to treatment

Limit of quantification is 2.6 log copies/mL; if assay didn’t detect virus, result reported as “<2/6 log copies/mL”; if assay detected presence of virus but was unable to quantify copies, result reported as “not quantified”

Renal allograft biopsy required to make a definitive diagnosis of BKVAN

BK Virus, Quantitative PCR, Blood 2002304
Method: Quantitative Real-Time Polymerase Chain Reaction

Viral load quantitation for treatment monitoring

Limit of quantification is 2.6 log copies/mL; if assay didn’t detect virus, result reported as “<2/6 log copies/mL”; if assay detected presence of virus but was unable to quantify copies, result reported as “not quantified”

 
BK Virus, Quantitative PCR, Urine 2002310
Method: Quantitative Real-Time Polymerase Chain Reaction

Detect BK virus infection and viral load quantitation

Limit of quantification is 2.6 log copies/mL; if assay didn’t detect virus, result reported as “<2/6 log copies/mL”; if assay detected presence of virus but was unable to quantify copies, result reported as “not quantified”

 
Cytology, Urologic 8209704
Method: Microscopy

May be helpful if negative, but PCR and biopsy are more sensitive

Positive test does not necessarily diagnose BKVAN

Biopsy or PCR is advised for positive test

Simian Virus 40 (SV-40) by Immunohistochemistry 2004137
Method: Immunohistochemistry

Aid in histologic diagnosis of BK virus

Stained and returned to client pathologist for interpretation; consultation available if needed