BK Virus

BK virus is a polyomavirus in the same family of viruses as JC virus and has become recognized as an important causal infectious agent in complications after kidney transplant and hematopoietic cell transplant (HCT).

Diagnosis

Indications for Testing

  • Previous renal transplant
  • Hemorrhagic cystitis in hematopoietic cell transplant (HCT) patients

Laboratory Testing

  • Polymerase chain reaction (PCR) – urine or blood
    • Blood
      • Quantitative testing provides objective estimate of viral load
    • Urine
      • More sensitive than urine cytology
      • Can distinguish BK virus from JC virus
      • Negative urine test has 100% predictive value (Kidney Disease: Improving Global Outcomes [KDIGO] guidelines, 2009)
      • Positive urine test must be followed up with serum test
        • Viruria alone does not increase risk of BK virus nephropathy (BKVN)
  • Urine cytology
    • Decoy cells – infected cells that demonstrate rounded nuclei with intranuclear basophilic inclusion on Pap stain bodies
      • Lack of decoy cells suggests no viral nephropathy
      • Presence of decoy cells suggests reactivation of virus but does not diagnose infection (100% sensitive; 20% positive predictive value)
        • Follow up with serum PCR test to demonstrate viremia

Histology

  • Definitive diagnosis requires biopsy and pathologist examination
  • Useful immunohistochemical stains may include Simian Virus 40 (SV-40) by Immunohistochemistry
  • For detailed descriptions, refer to ARUP’s Immunohistochemistry Stain Offerings

Differential Diagnosis

  • Other viral infections (eg, cytomegalovirus)
  • Rejection (acute or chronic)
  • Malignancy

Screening

  • Renal transplant patient recommendations as per American Society of Transplantation (AST, 2009) and Kidney Disease: Improving Global Outcomes (KDIGO, 2009) guidelines
    • Screen with serum for BK virus using nucleic acid testing (eg, polymerase chain reaction [PCR])
    • May initially screen with urine cytology (to detect decoy cells) or quantitative urine PCR
    • Duration and schedule for screening differ between societies
      • KDIGO – monthly first 3-6 months, then every 3 months until >1 year posttransplant
      • AST – every 3 months for first 2 years, then annually until 5th year posttransplant
  • Early identification of BK virus infection may allow preemptive measure to prevent BK virus nephropathy (BKVN)
  • Hematopoietic stem cell transplant patients recommendations as per American Society of Blood and Bone Marrow Transplantation (Tomblyn, 2009) – no evidence to support routine screening for BK virus

Monitoring

Polymerase chain reaction (PCR) quantitative – expect reduction in viremia with treatment

Background

Epidemiology

  • Prevalence
    • Primary BK virus infection generally occurs in early childhood without specific symptoms
      • 90% of population is seropositive
    • Transplant patients
    • Reactivation of BK virus
    • Populations affected
      • 1-5% of kidney transplant patients
      • Small percentage of hematopoietic cell transplant (HCT) patients
  • Transmission of primary infection
    • Presumably transmitted via respiratory droplets
    • Other speculated modes of transmission include urine, semen, blood transfusion, and organ transplantation

Organism

  • Double-stranded DNA virus
  • Human polyomavirus (genetically similar to JC virus)
  • BK virus becomes latent in the kidneys and urinary tract after primary infection
    • Reactivated BK virus infection may occur with immunosuppression

Clinical Presentation

  • Clinical BK virus disease is rare in immunocompetent adults
  • BK virus diseases
    • Renal transplant patients – nephropathy with risk of graft loss
      • BK virus allograft nephropathy (BKVN)​
        • Tubulointerstitial nephritis – most common manifestation
        • May lead to irreversible graft failure in large number of patients
      • ​New immunosuppressive regimens may increase the risk of BKVN
      • Majority of BKVN occurs in first 2 years posttransplantation (Kidney Disease: Improving Global Outcomes, 2009)
    • HCT patients – hemorrhagic cystitis and renal impairment
      • BKVN is uncommon in HCT patients (Tomblyn, 2009)
      • Hemorrhagic cystitis – more common in allogeneic versus autologous transplants

ARUP Lab Tests

Primary Tests

Detect and quantify BK virus in blood or urine

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”

Detect and quantify BK virus in blood 

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”

Detect and quantify BK virus in urine

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”

Detect BK virus infection in immunocompromised patients

This test is used for all nongynecologic sources EXCEPT specimens obtained by fine needle aspiration (FNA); for FNA specimens, refer to the cytology, fine needle aspirate test

Aid in histologic diagnosis of BK virus

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

Medical Experts

Contributor

Chadwick

Barbara Chadwick, MD
Associate Professor of Anatomic Pathology, University of Utah
Medical Director, Anatomic Pathology and Cytopathology, ARUP Laboratories
Contributor
Contributor

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®