BK Virus

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

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

Laboratory Testing

  • Polymerase chain reaction (PCR) assay – 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 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)
        • Follow up with serum PCR test to demonstrate viremia

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 (eg, cytomegalovirus)
  • Rejection (acute or chronic)
  • Malignancy
  • 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 (Tomblyn, 2009)
    • No evidence to support routine screening for BK virus
  • Use polymerase chain reaction (PCR) quantitative – expect reduction in viremia with treatment

BK virus is a polyoma virus 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 transplantation (HCT).

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 are affected
      • 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 (KDIGO, 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
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.

BK Virus, Quantitative PCR 0090067
Method: Quantitative Real-Time Polymerase Chain Reaction

Recommended Use 

Detects BK virus infection and viral load quantitation

Limitations 

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”

Follow-up 

Renal allograft biopsy required to make a definitive diagnosis of BKVAN

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

Recommended Use 

Detects BK virus infection and viral load quantitation

Limitations 

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

Recommended Use 

Detects BK virus infection and viral load quantitation

Limitations 

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”

Follow-up 

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

Cytology, Non-Gynecologic 2000623
Method: Microscopy

Recommended Use 

Detects 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

Limitations 

Less sensitive than PCR

Follow-up 

With positive test, consider biopsy or PCR

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

Recommended Use 

Aid in histologic diagnosis of BK virus

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

Guidelines

Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009; 9 Suppl 3: S1-155. PubMed

Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JH, Boeckh MJ, Boeckh MA, Center for International Blood and Marrow Research, National Marrow Donor program, European Blood and MarrowTransplant Group, American Society of Blood and Marrow Transplantation, Canadian Blood and Marrow Transplant Group, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, Association of Medical Microbiology and Infectious Disease Canada, Centers for Disease Control and Prevention. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009; 15(10): 1143-238. PubMed

General References

Bohl DL, Brennan DC. BK virus nephropathy and kidney transplantation. Clin J Am Soc Nephrol. 2007; 2 Suppl 1: S36-46. PubMed

Bonvoisin C, Weekers L, Xhignesse P, Grosch S, Milicevic M, Krzesinski J. Polyomavirus in renal transplantation: a hot problem. Transplantation. 2008; 85(7 Suppl): S42-8. PubMed

Boothpur R, Brennan DC. Human polyoma viruses and disease with emphasis on clinical BK and JC. J Clin Virol. 2010; 47(4): 306-12. PubMed

Cimbaluk D, Pitelka L, Kluskens L, Gattuso P. Update on human polyomavirus BK nephropathy. Diagn Cytopathol. 2009; 37(10): 773-9. PubMed

Harkensee C, Vasdev N, Gennery AR, Willetts IE, Taylor C. Prevention and management of BK-virus associated haemorrhagic cystitis in children following haematopoietic stem cell transplantation--a systematic review and evidence-based guidance for clinical management. Br J Haematol. 2008; 142(5): 717-31. PubMed

Masutani K. Current problems in screening, diagnosis and treatment of polyomavirus BK nephropathy. Nephrology (Carlton). 2014; 19 Suppl 3: 11-6. PubMed

Morrison BJ, Labo N, Miley WJ, Whitby D. Serodiagnosis for tumor viruses Semin Oncol. 2015; 42(2): 191-206. PubMed

Weinberg GA, Mian AN. BK virus nephropathy and other polyoma virus infections. Pediatr Infect Dis J. 2010; 29(3): 257-60. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Emerson LL, Carney HM, Layfield LJ, Sherbotie JR. Collecting duct carcinoma arising in association with BK nephropathy post-transplantation in a pediatric patient. A case report with immunohistochemical and in situ hybridization study. Pediatr Transplant. 2008; 12(5): 600-5. PubMed

Medical Reviewers

Chadwick, Barbara E., MD, Medical Director, Cytology, and Staff Pathologist, Surgical Pathology at ARUP Laboratories; Assistant Professor of Anatomic Pathology, University of Utah

Hillyard, David R., MD, Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Professor of Clinical Pathology, Adjunct Professor of Biology, University of Utah

Salama, Mohamed E., MD, Medical Director, Hematopathology and Immunohistochemistry Staining at ARUP Laboratories; Associate Professor of Clinical Pathology, Director of Hematopathology Fellowship Program, University of Utah

Last Update: August 2016

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