Abstract
The last decade has witnessed the introduction of several potent immunosuppressive agents in the field of transplant medicine. Contemporaneously, infection with BK virus (BKV) has emerged as an important complication of immunosuppression and an important cause of allograft loss after kidney transplantation. Rhandhawa et al reported the first case of BKV associated nephropathy (BKVN) in the modern era of transplantation, in 1995. Since then there has been a resurgence of interest in the epidemiology, biology and pathogenic associations of BKV especially in transplant medicine. Up to 90% of adults have serologic evidence of exposure to BKV. However, only 1–5% of normal healthy adults excrete the virus in the urine (asymptomatic viruria). Thus, for a vast majority of the population, the virus remains perfectly latent and this state of latency is of no obvious consequence. Almost all instances of disease by the BKV have been seen in immunocompromised patients. In recent years, BKV has been associated with nephropathy (BKVN) in about 5% of renal transplant patients. Once established, the disease may result in allograft loss in 45–70% of patients. Although not proven by any prospective study, BKVN causing allograft failure has been linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil. This is noteworthy, as both these agents have been used increasingly as the primary maintenance immunotherapy in solid organ transplantation since their introduction around 1990. In addition to the immunosuppressed state, other factors like allograft injury have been thought to be involved in the pathogenesis of the disease. We believe that reactivation of the BKV from its latent state crucially depends on an immunocompromised state but more factors than one dictate precipitation of clinical end organ disease.
In this Chapter, we will discuss the clinical aspects of BKV infection in the renal transplant recipient. We will focus on the role of immunosuppression as a seminal factor allowing replication of the virus. Not all patients who have replicating BKV go on to develop nephropathy: we will discuss other host factors that may constitute a’ second hit’ allowing replicating BKV to precipitate BKVN. Results of our recently concluded prospective study on the issue of current immunosuppressive agents in the development of BKVN will be discussed. Finally, based on our experience, we will provide some guidelines for early diagnosis and management of this disease.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Shah KV. Polyomaviruses. In: Fields BN, Knipe DM, Howley PM, eds. Fields Virology. 3rd ed. Philadelphia: Lippincott-Raven, 1996:2027–2043.
Gardner SD. Prevalence in England of antibody to human polyoma virus (BK). Br Med J 1973; 1:77–8.
Shah KV, Daniel RW, Warszawski RM. High prevalence of antibodies to BK virus, an SV 40 related papovavirus, in residents of Maryland. J Infect Dis 1973; 128:784–7.
Portolani M, Marzocchi A, Barbanti-Brodano G et al. Prevalence in Italy of antibodies to a new human papova virus (BK Virus). J Med Microbiol 1974; 7:543–6.
Goudsmid J, Van Dillen WP, van Strein 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; 10:91–9.
Hashida Y, Gaffney PC, Younis EJ. Acute hemorrhagic cystitis of childhood and and papova-like particles. J Paedriatics 1976; 89:85–7.
Saitoh K, Sugae N, Koike N et al. Diagnosis of childhood BK virus cystitis by electron microscopy and PCR. J Clin Path 1993; 46:773–5.
Voltz R, Jager G, Seelos K et al. BK virus encephalitis in an immunocompetent patient. Arch Neurol 1996; 53:101–3.
Howell DN, Smith SR, Butterly DW et al. Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients. Transplantation 1999; 68(9):1279–88.
Drachenberg CB, Papadimitriou JC, Wali R et al. Polyoma virus allograft nephropathy: Ultrastructural features from viral cell entry to lysis. Am J of Transplantation 2003; 3:1383.
Hirsch HH. Polyoma BK nephropathy: A (Re) emerging complication in renal transplantation. Am J of Transplantation 2002; 2:25–30.
Chang D, Wang M, Ou WC et al. Genotypes of human polyomaviruses in urine samples of pregnant women in Taiwan. J Med Virol 1996; 48(1):95–101.
Coleman DV, Gardner SD, Mulholland C et al. Human polyomavirus in pregnancy. A model for the study of defense mechanisms to virus reactivation. Clin Exp Immunol 1983; 53(2):289–96.
Borgatti M, Costanzo F, Portolani M et al. Evidence for reactivation of persistent infection during pregnancy and lack of congenital transmission of BK virus, a human papovavirus. Microbiologica 1979; 2:173–8.
Kahan AV, Coleman DV, Koss LG. Activation of human polyomavirus infection-detection by cytologic techniques. Am J Clin Pathol 1980; 74(3):326–32.
Kitamura T, Aso Y, Kuniyoshi N et al. High incidence of urinary JC virus excretion in nonimmunosuppressed older patients. J Infect Dis 1990; 161(6):1128–33.
Azzi A, Ciappi S, De Santis R et al. Hemorrhagic cystitis associated with BKV in patients with refractory acute lymphoblastic leukemia. Am J Hematol 1996; 52(2):121–2.
De Silva LM, Bale P, de Courcy J et al. Renal failure due to BK virus infection in an immunodeficient child. J Med Virol 1995; 45(2):192–6.
Rosen S, Harmon W, Krensky AM et al. Tubulo-interstitial nephritis associated with polyomavirus (BK type) infection. N Engl J Med 1983; 308(20):1192–6.
Boldorini R, Zorini EO, Viagano P et al. Cytologic and biomolecular diagnosis of polyoma virus infection in urine specimens of HIV-positive patients. Acta Cytologica 2000; 44(2):205–10.
Smith RD, Galla JH, Skahan K et al. Tubulointerstitial nephritis due to a mutant polyomavirus BK virus strain, BKV (Cin), causing end-stage renal disease. J Clin Microbiol 1998; 36(6):1660–5.
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.
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):807–11.
Nickeleit V, Hirsch HH, Zeiler M et al. BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dial Transplant 2000; 15(3):324–32.
Atencio LA, Shadan FF, Zhou XJ et al. Adult mouse kidneys become permissive to acute polyomavirus infection and reactivate persistent infections in response to cellular damage and re generation. J Virol 1993; 67(3):1424–32.
Nickeleit V, Hirsch H, Binet I et al. Polyomavirus infection of renal allograft recipients: From latent infection to manifest disease. J Am Soc Nephrol 1999; 10:1080–1089.
Drachenberg RC, Drachenberg CB, Papadimitriou JC et al. Morphological spectrum of polyoma virus disease in renal allografts: Diagnostic accuracy of urine cytology. Am J Transplant 2001; 1:378–381.
Hirsch HH, Knowles W, Dickenmann M et al. Prospective study of polyomavirus type BK replication and nephropathy in renal transplant recipients. N Engl J Med 2002; 347:488–496.
Bedi A, Miller CB, Hanson JL et al. Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation. J Clin Oncol 1995; 13(5):1103–9.
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.
Purighalla R, Shapiro R, McCauley J et al. BK Virus infection in a kidney allograft diagnosed by needle biopsy. Am J Kidney Dis 1995; 26:671–673.
Binet I, Nickeleit V, Hirsch HH et al. Polyomavirus disease under new immunosuppressive drugs: A cause of renal graft dysfunction and graft loss. Transplantation 1999; 67(6):918–922.
Randhawa PS, Finkelstein S, Scantlebury V et al. Human polyomavirus-associated interstitial ne phritis in the allograft kidney. Transplantation 1999; 67(1):103–109.
Barri YM, Ahmad I, Ketel BL et al. Polyoma viral infection in renal transplantation: The role of immunosuppressive therapy. Clin Transplant 2001; 15(4):240–246.
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.
Hirsch HH, Mohaupt M, Klimkait T. Prospective monitoring of BK virus load after discontinuing sirolimus treatment in a renal transplant patient with BK virus nephropathy. J Infect Dis 2001; 184:1494.
Ramos E, Drachenberg CB, Portocarrero M et al. BK virus nephropathy diagnosis and treatment: Experience at the University of Maryland renal transplant program. Clin Transpl 2002; 143–153.
Celik B, Shapiro R, Vats A et al. Polyomavirus allograft nephropathy: Sequential assessment of histologic viral load, tubulitis and graft function following changes in immunosuppression. Am J Transplantation 2003; 3:1378–1382.
Buehrig CK, Lager DJ, Stegall MD et al. Influence of surveillance renal allograft biopsy on diagnosis and prognosis of polyomavirus-associated nephropathy. Kidney Int 2003; 64(2):665–673.
Nickeleit V, Klimkait T, Binet IF et al. Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy. N Engl J Med 2000; 342(18):1309–1315.
Limaye AP, Jerome KR, Kuhr CS et al. Quantitation of BK virus load in serum for the diagnosis of BK virus-associated nephropathy in renal transplant recipients. J Infect Dis 2001; 183(11):1669–1672.
Randhawa PS, Demetris AJ. Nephropathy due to polyomavirus type BK. N Engl J Med 2000; 342(18):1309–1915.
Ahuja M, Cohen EP, Dayer AM et al. Polyoma virus infection after renal transplantation. Use of immunostaining as a guide to diagnosis. Transplantation 2001; 71(7):896–899.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Eurekah.com and Springer Science+Business Media
About this chapter
Cite this chapter
Agha, I., Brennan, D.C. (2006). BK Virus and Immunosuppressive Agents. In: Ahsan, N. (eds) Polyomaviruses and Human Diseases. Advances in Experimental Medicine and Biology, vol 577. Springer, New York, NY. https://doi.org/10.1007/0-387-32957-9_12
Download citation
DOI: https://doi.org/10.1007/0-387-32957-9_12
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-29233-5
Online ISBN: 978-0-387-32957-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)