BK Virus

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