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, Urologic (To order, use Test code 2000623, NG REQUEST) 8209704
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