BK Virus

Diagnosis

Indications for Testing

  • Renal transplant patients
  • Hematopoietic cell transplant (HCT) patient with hemorrhagic cystitis

Laboratory Testing

  • Polymerase chain reaction (PCR) assay – urine or blood
    • More sensitive than urine cytology
    • Quantitative testing provides objective estimate of viral load
      • Can distinguish BK virus from JC virus in urine
      • Negative urine test has 100% predictive value (Kidney Disease Improving Global Outcome Guidelines [KDIGO], 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)

Histology

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

Differential Diagnosis

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

Screening

  • Renal transplant patient recommendations as per American Society of Transplantation and Kidney Disease Improving Global Outcome Guidelines (KDIGO, 2009)
    • Screen with serum for BK virus using nucleic acid testing (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 (2009)
    • No evidence to support routine screening for BK virus

Monitoring

  • Use polymerase chain reaction (PCR) quantitative – expect reduction in viremia with treatment

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 virus infection generally occurs in childhood without specific symptoms
      • 90% of population is seropositive
    • Transplant patients (reactivation of BK virus)
      • 1-5% of kidney transplant patients are affected
      • Small percentage of hematopoietic cell transplant (HCT) patients
  • Transmission of primary infection
    • 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 (usually in childhood), BK virus becomes latent in the kidneys and urinary tract
    • Reactivated BK virus infection occurs with immunosuppression

Clinical Presentation

  • Clinical BK virus disease is rare in immunocompetent adults
  • BK virus infections are a cause of morbidity and mortality for patients with hematologic  and renal transplants
  • Illnesses caused by BK virus
    • Renal transplant patients – nephropathy and graft loss
      • BK virus allograft nephropathy (BKVN) – present in up to 8% of kidney transplant patients
        • Tubulointerstitial nephritis – most common manifestation
        • May lead to irreversible graft failure in 40-50% of patients
      • New immunosuppressive regimens may increase the risk of BKVN
      • 95% of BKVN occurs in first 2 years posttransplantation (KDIGO 2009)
    • HCT patients – hemorrhagic cystitis and renal impairment
      • BKVN is uncommon in HCT patients
      • Hemorrhagic cystitis – more common in allogeneic versus autologous transplants

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

Detects 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”

Renal allograft biopsy required to make a definitive diagnosis of BKVAN

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

Detects 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”

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

Detects 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”

With positive urine test, serum quantification of BK virus is necessary

Cytology, Non-Gynecologic 2000623
Method: Microscopy

Detects BK virus infection in immunocompromised patients

Less sensitive than PCR

With positive test, consider biopsy or PCR

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