Patients who have undergone renal transplantation are known to be susceptible to upper respiratory tract infections and pneumonia, both viral and bacterial, because of their immunocompromised states. Pneumonia associated with the polyomavirus BK (BKV), however, has been reported infrequently. We report the case of a patient who had undergone a renal transplant years earlier and was on an immunosuppressive therapy regimen when she developed symptoms of BKV-associated pneumonia.

Case report
A 53-year-old woman reported symptoms of an upper respiratory tract infection—high-grade fever, chills, and nasal congestion—that had progressed to a productive cough, yielding sputum. Of note, she had undergone a cadaveric pancreatic transplant in 2002 and a renal transplant from a living, blood-related donor in 2003 and was taking mycophenolate mofetil.

The patient was discovered to have a right middle-lobe infiltrate. Her blood, urine, and sputum cultures were negative for bacteria. Viral workup included tests for respiratory syncytial virus and cytomegalovirus, which were also negative. The patient’s urine was tested for BKV using the DNA polymer chain reaction (PCR) technique. The results were positive, identifying a BKV load of 2 x 10⁶ copies/mL. This prompted a quantitative PCR analysis for BKV DNA in serum, which showed 6.4 x 10⁵ copies/mL. During this time, bronchoalveolar lavage was performed, which was negative for bacterial colonies but showed 640 colonies/mL for BKV DNA by PCR.

The patient was instructed to discontinue taking mycophenolate mofetil, and cidofovir was prescribed. According to PCR analysis, the BKV DNA peaked at 4.7 x 10⁶ copies/mL over the next 2 weeks before trending downward. After 6 months, levels were no longer detectable.

Discussion
BKV is a double-stranded DNA polyomavirus, named for the initials of the first patient from whom it was isolated in 1971.^1,2 BKV can be transmitted through contact with infected blood or respiratory and sexual fluids and by transplacental route.^3-6 Primary infection with this virus is generally asymptomatic and usually occurs in children, manifesting as a nonspecific upper respiratory tract infection.^7,8 

Once a primary infection has occurred, BKV can remain dormant in many sites including the liver, kidneys, eyes, lungs, and brain.^3,5,9 The kidneys are the most common site of latent infection, followed by the brain (Figure 1); other reported latent sites include the tonsils, nasopharynges, spermatozoa, pituitary gland, lungs, liver, and bones.¹⁰ Within these host cells’ viral genome, BKV may remain episomal or become integrated into the host-cell genome and out of reach of the host cell’s immune system.

BKV can be reactivated in states of relative or absolute immunodeficiency, at a cellular rather than humoral level, and cause disease.² Reactivation is seen mostly in patients with acquired immunodeficiency syndrome (AIDS) or those who have undergone organ transplants. The renal manifestations of BKV are nephritis, hemorrhagic and nonhemorrhagic cystitis, and ureteric stenosis.^11-14 Its pulmonary manifestations are pneumonitis and acute, nonspecific upper respiratory infection.^15-17

The kidneys are the most commonly reported site of BKV reactivation (Figure 2). Disease presentations include hematuria; acute, late-onset, long-duration hemor- rhagic cystitis (which should be differentiated from early-onset, transient cystitis caused by cyclophosphamide¹⁸); ureteric stenosis¹²; tubulointerstitial nephritis¹⁹; and allograft nephropathy, associated most commonly with immunosuppressant agents such as tacrolimus and mycophenolate mofetil.^20,21 

BKV-induced kidney lesions have a specific pathologic appearance. Microscopically, they appear as sclerosed glomeruli, atrophic and necrotic tubules, and interstitial fibrosis associated with a mononuclear cell infiltrate.²² Intranuclear inclusions test positive for BKV in the tubular cells and fibroblasts. Gross appearance of the kidneys includes circumscribed cortical scars and streaky fibrosis of the medulla.

BKV-related pulmonary disease has been reported most often in children and AIDS patients. Manifestations include acute, nonspecific upper respiratory infection and interstitial pneumonitis, which has been reported to progress to acute respiratory distress syndrome.^15,22,23 Pathologically, fibrosis is the most common finding, but interalveolar aggregates of pneumocytes, focal hemorrhages, and mononuclear cell infiltrates have also been observed.^2,17 Fibrocytes and pneumocytes have been shown to contain BKV DNA.

Traditionally, BKV arising in renal transplant patients has been treated by reducing the patient’s immunosuppressive therapy; however, 30% to 40% of these patients ultimately suffer allograft loss.²⁴ Cidofovir is an antiviral agent that has been effective in low doses (0.25 mg/kg, administered intravenously) at clearing BKV DNA from the patient’s blood and allograft, stabilizing renal function without significant toxicity.²⁴ The addition of cidofovir, concurrent with a reduction in immunosuppressant therapy, has been shown to reduce graft rejection and provide faster resolution of BKV.

References
1. Gardner SD, Field AM, Coleman DV, et al. New human papovavirus (BK) isolated from urine after renal transplantation. Lancet. 1971;1(7712):1253-1257.

2. Reploeg MD, Storch GA, Clifford DB. BK virus: a clinical review. Clin Infect Dis. 2001;33(2):191-202.

3. Monini P, Rotola A, de Lellis L, et al. Latent BK virus infection and Kaposi’s sarcoma pathogenesis. Int J Cancer. 1996;66(6): 717-722.

4. Shah KV, Daniel RW, Warszawski RM. High prevalence of antibodies to BK virus, an SV40-related papovavirus, in residents of Maryland. J Infect Dis. 1973;128(6):784-787.

5. Sundsfjord A, Spein AR, Lucht E, et al. Detection of BK virus DNA in nasopharyngeal aspirates from children with respiratory infections but not in saliva from immunodeficient and immunocompetent adult patients. J Clin Microbiol. 1994;32(5):1390-1394.

6. Taguchi F, Nagaki D, Saito M, et al. Transplacental transmission of BK virus in humans. Jpn J Microbiol. 1975;19(5):395-398.

7. Goudsmit J, Wertheim-van Dillen P, van Strien A, et al. The role of BK virus in acute respiratory tract disease and the presence of BKV DNA in tonsils. J Med Virol. 1982;10(2):91-99.

8. Mantyjarvi RA, Meurman OH, Vihma L, et al. A human papovavirus (BK), biological properties and seroepidemiology. Ann Clin Res. 1973;5(5):283-287.

9. Vago L, Cinque P, Sala E, et al. JCV-DNA and BKV-DNA in the CNS tissue and CSF of AIDS patients and normal subjects. Study of 41 cases and review of the literature. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;12(2):139-146.

10. De Mattei M, Martini F, Tognon M, et al. Polyomavirus latency and human tumors. J Infect Dis. 1994;169(5):1175-1176.

11. Coleman DV, Mackenzie EF, Gardner SD, et al. Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients. J Clin Pathol. 1978;31(4):338-347.

12. Gardner SD, MacKenzie EF, Smith C, et al. Prospective study of the human polyomaviruses BK and JC and cytomegalovirus in renal transplant recipients. J Clin Pathol. 1984;37(5):578-586.

13. Padgett BL, Walker DL, Desquitado MM, et al. BK virus and nonhaemorrhagic cystitis in a child. Lancet. 1983;1(8327):770.

14. Saitoh K, Sugae N, Koike N, et al. Diagnosis of childhood BK virus cystitis by electron microscopy and PCR. J Clin Pathol. 1993; 46(8): 773-775.

15. Sandler ES, Aquino VM, Goss-Shohet E, et al. BK papova virus pneumonia following hematopoietic stem cell transplantation. Bone Marrow Transplant. 1997;20(2):163-165.

16. Shah KV. Polyomaviruses. In: Fields BN, Knipe DM, eds. Virology. 2d ed. New York, NY: Raven Press; 1990:1609-1623.

17. Vallbracht A, Lohler J, Gossmann J, et al. Disseminated BK- type polyomavirus infection in an AIDS patient associated with central nervous system disease. Am J Pathol. 1993;143(1):29-39.

18. Apperley JF, Rice SJ, Bishop JA, et al. Late-onset hemorrhagic cystitis associated with urinary excretion of polyomaviruses after bone marrow transplantation. Transplantation. 1987;43(1): 108-112.

19. Nebuloni M, Tosoni A, Boldorini R, et al. BK virus renal infection in a patient with the acquired immunodeficiency syndrome. Arch Pathol Lab Med. 1999;123(9): 807-811.

20. Andrews CA, Shah KV, Daniel RW, et al. A serological investigation of BK virus and JC virus infections in recipients of renal allografts. J Infect Dis. 1988;158(1):176-181.

21. Coleman DV, Gardner SD, Field AM. Human polyomavirus infection in renal allograft recipients. Br Med J. 1973;3(5876): 371-375.

22. Cubukcu-Dimopulo O, Greco A, Kumar A, et al. BK virus infection in AIDS. Am J Surg Pathol. 2000;24(1):145-149. 

23. Goudsmit J, Baak ML, Sleterus KW, et al. Human papovavirus isolated from urine of a child with acute tonsillitis. Br Med J (Clin Res Ed). 1981;283(6303): 1363-1364.

24. Howell DN, Smith SR, Butterly DW, et al. Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients. Transplantation. 1999;68(9):1279-1288.