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FeedbackBK 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)
- Blood
- 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
- Decoy cells – infected cells that demonstrate rounded nuclei with intranuclear basophilic inclusion on Pap stain bodies
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
- Primary BK virus infection generally occurs in early childhood without specific symptoms
- 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)
- BK virus allograft nephropathy (BKVN)
- HCT patients – hemorrhagic cystitis and renal impairment
- BKVN is uncommon in HCT patients (Tomblyn, 2009)
- Hemorrhagic cystitis – more common in allogeneic versus autologous transplants
- Renal transplant patients – nephropathy with risk of graft loss
ARUP Laboratory 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”
Method
Quantitative Real-Time Polymerase Chain Reaction
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”
Method
Quantitative Real-Time Polymerase Chain Reaction
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”
Method
Quantitative Real-Time Polymerase Chain Reaction
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
Method
Microscopy
Aid in histologic diagnosis of BK virus
Stained and returned to client pathologist for interpretation; consultation available if needed
Method
Immunohistochemistry
Medical Experts
Contributor
Chadwick
Associate Professor of Anatomic Pathology, University of Utah
Medical Director, Anatomic Pathology and Cytopathology, ARUP Laboratories
Contributor
Hillyard
Professor of Pathology, University of Utah
Medical Director, Molecular Infectious Diseases, ARUP Laboratories
Contributor
Miles
Associate Professor of Clinical Pathology, University of Utah
Section Chief, Hematopathology, ARUP Laboratories
References
Additional Resources
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Bohl DL, Brennan DC. BK virus nephropathy and kidney transplantation. Clin J Am Soc Nephrol. 2007; 2 Suppl 1 S36-46.
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Bonvoisin C, Weekers L, Xhignesse P , et al. Polyomavirus in renal transplantation: a hot problem. Transplantation. 2008; 85 (7 Suppl): S42-8.
PubMed
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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
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Cimbaluk D, Pitelka L, Kluskens L , et al. Update on human polyomavirus BK nephropathy. Diagn Cytopathol. 2009; 37 (10): 773-9.
PubMed
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Harkensee C, Vasdev N, Gennery AR , et al. 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
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Hirsch HH, Randhawa P, AST Infectious Diseases Community of Practice. BK virus in solid organ transplant recipients. Am J Transplant. 2009; 9 Suppl 4 S136-46.
PubMed
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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
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Masutani K. Current problems in screening, diagnosis and treatment of polyomavirus BK nephropathy. Nephrology (Carlton). 2014; 19 Suppl 3 6-Nov.
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Morrison BJ, Labo N, Miley WJ, et al. Serodiagnosis for tumor viruses. Semin Oncol. 2015;42(2):191-206.
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Tomblyn M, Chiller T, Einsele H , et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009; 15 (10): 1143-238.
PubMed
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Weinberg GA, Mian AN. BK virus nephropathy and other polyoma virus infections. Pediatr Infect Dis J. 2010; 29 (3): 257-60.
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Resources from the ARUP Institute for Clinical and Experimental Pathology®
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Emerson LL, Carney HM, Layfield LJ , et al. 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
