Skip to main content
SpringerLink
Log in
Book cover

Polyomaviruses and Human Diseases pp 160–173Cite as

Polyomavirus-Associated Nephropathy in Renal Transplantation

Critical Issues of Screening and Management

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 577))

Abstract

Polyomavirus-associated nephropathy (PVAN) is an emerging disease in renal transplant patients with variable prevalence of 1–10% and graft loss up to 80%. BK virus (BKV) is the primary etiologic agent, but JC virus (JCV) and possibly simian virus SV40 may account for some cases. Intense immunosuppression is viewed as the most important risk factor. However, the preferential manifestation in renal transplants as compared to other allografts or to autologous kidneys of other organ transplants suggests that organ determinants and immunologic factors synergize: Renal tubular epithelial cells and their compensatory proliferation to restore tubular integrity after immunologic, ischemic or toxic injury may provide the critical cellular milieu supporting polyomavirus replication while immune control is impaired due to maintenance immunosuppression, anti-rejection treatment and HLA-mismatches. Patient determinants (older age, male gender, seronegative recipient), and viral factors (genotype, serotype) may have a contributory role. The definitive diagnosis of PVAN requires allograft biopsy which is, however, challenged by (i) limited sensitivity due to (multi-)focal involvement (sampling errors); (ii) varying presentations with cytopathic-inflammatory and/or fibrotic/scarring patterns; (iii) coexisting acute rejection which is difficult to differentiate, but impacts on intervention strategies. Screening for polyomavirus replication in the urine and in the plasma complements allograft biopsy by high sensitivity and allows for noninvasive monitoring. Thus, we suggest a terminology similar to invasive fungal diseases where viruria (“decoy cells”) defines patients at risk (“possible PVAN”) who should be evaluated for plasma viral load. Increasing BK viremia (> 10,000 copies/mL) or urine VP-1 mRNA (>6.5×105 copies/ng total RNA) load defines “presumptive PVAN” for which an intervention of reducing immunosuppression should be considered even if the diagnosis could not be confirmed by allograft biopsy (“definitive PVAN”). The response to intervention should be monitored using plasma DNA or urine mRNA load.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gardner SD, Field AM, Coleman DV et al. New human papovavirus (B.K.) isolated from urine after transplantation. Lancet 1971; i:1253–1257.

    Article  Google Scholar 

  2. Padgett BL, Walker DL, Zu Rhein GM et al. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1971; i:1257–1260.

    Article  Google Scholar 

  3. 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.

    Article  PubMed  CAS  Google Scholar 

  4. 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; 67:918–922.

    Article  PubMed  CAS  Google Scholar 

  5. Drachenberg CB, Beskow CO, Cangro CB et al. Human polyoma virus in renal allograft biopsies: Morphological findings and correlation with urine cytology. Hum Pathol 1999; 30:970–977.

    Article  PubMed  CAS  Google Scholar 

  6. Mackenzie EF, Poulding JM, Harrison PR et al. Human polyoma virus (HPV)-a significant pathogen in renal transplantation. Proc Eur Dial Transplant Assoc 1978; 15:352–360.

    PubMed  CAS  Google Scholar 

  7. Hirsch HH. Polyomavirus BK nephropathy: A (re)emerging complication in renal transplantation. Am J Transplant 2002; 2:25–30.

    Article  PubMed  Google Scholar 

  8. Rosen S, Harmon W, Krensky AM et al. Tubulo-interstitial nephritis associated with polyomavirus (BK type) infection. N Engl J Med 1983; 308:1192–1196.

    Article  PubMed  CAS  Google Scholar 

  9. Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis 2003; 3:611–623.

    Article  PubMed  Google Scholar 

  10. Pappo O, Demetris AJ, Raikow RB et al. Human polyoma virus infection of renal allografts: Histopathologic diagnosis, clinical significance, and literature review. Mod Pathol 1996; 9:105–109.

    PubMed  CAS  Google Scholar 

  11. Mathur VS, Olson JL, Darragh TM et al. Polyomavirus-induced interstitial nephritis in two renal transplant recipients: Case reports and review of the literature. Am J Kidney Dis 1997; 29:754–758.

    Article  PubMed  CAS  Google Scholar 

  12. Randhawa PS, Finkelstein S, Scantlebury V et al. Human polyoma virus-associated interstitial nephritis in the allograft kidney. Transplantation 1999; 67:103–109.

    Article  PubMed  CAS  Google Scholar 

  13. Knowles WA, Pipkin P, Andrews N et al. Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40. J Med Virol 2003; 71:115–123.

    Article  PubMed  Google Scholar 

  14. Shah KV, Daniel R, Warszawski R. High prevalence of antibodies to BK virus, an SV40-related papovavirus, in residents of Maryland. J Infect Dis 1973; 128:784–787.

    PubMed  CAS  Google Scholar 

  15. zur Hausen H. SV40 in human cancers—an endless tale? Int J Cancer 2003; 107:687.

    Article  PubMed  CAS  Google Scholar 

  16. Fishman JA. BK virus nephropathy—polyomavirus adding insult to injury. N Engl J Med 2002; 347:527–530.

    Article  PubMed  Google Scholar 

  17. Moens U, Rekvig OP. Molecular biology of BK virus and clinical and basic aspectes of BK virus renal infection. In: Khalili K, Stoner GL, eds. Human Polyomaviruses: Molecular and clinical perspectives. New York: Wiley-Liss, 2001:215–226.

    Google Scholar 

  18. Tognon M, Corallini A, Martini F et al. Oncogenic transformation by BK virus and association with human tumors. Oncogene 2003; 22:5192–5200.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    Google Scholar 

  20. 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; 64:665–673.

    Article  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. Mengel M, Marwedel M, Radermacher J et al. Incidence of polyomavirus-nephropathy in renal allografts: Influence of modern immunosuppressive drugs. Nephrol Dial Transplant 2003; 18:1190–1196.

    Article  PubMed  CAS  Google Scholar 

  23. Trofe J, Gaber LW, Stratta RJ et al. Polyomavirus in kidney and kidney-pancreas transplant recipeents. Transpl Infect Dis 2003; 5:21–28.

    PubMed  CAS  Google Scholar 

  24. Ginevri F, De Santis R, Comoli P et al. Polyomavirus BK infection in pediatric kidney-allograft recipients: A single-center analysis of incidence, risk factors, and novel therapeutic approaches. Transplantation 2003; 75:1266–1270.

    Article  PubMed  CAS  Google Scholar 

  25. Rahamimov R, Lustig S, Tovar A et al. BK polyoma virus nephropathy in kidney transplant recipient: The role of new immunosuppressive agents. Transplant Proc 2003; 35:604–605.

    Article  PubMed  CAS  Google Scholar 

  26. Kang YN, Han SM, Park KK et al. BK virus infection in renal allograft recipients. Transplant Proc 2003; 35:275–277.

    Article  PubMed  CAS  Google Scholar 

  27. Ramos E, Drachenberg CB, Papadimitriou JC et al. Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol 2002; 13:2145–2151.

    Article  PubMed  Google Scholar 

  28. Li RM, Mannon RB, Kleiner D et al. BK virus and SV40 coinfection in polyomavirus nephropathy. Transplantation 2002; 74:1497–1504.

    Article  PubMed  Google Scholar 

  29. Maiza H, Fontaniere B, Dijoud F et al. Graft dysfunction and polyomavirus infection in renal allograft recipients. Transplant Proc 2002; 34:809–811.

    Article  PubMed  CAS  Google Scholar 

  30. Moriyama T, Namba Y, Kyo M et al. Prevalence and characteristics of biopsy-proven BK virus nephropathy in Japanese renal transplant patients: Analysis in Protocol, NonEpisode and Episode Biopsies. J Am Soc Nephrol 2003; 14:F-PO571.

    Google Scholar 

  31. Drachenberg CB, Papadimitriou JC, Hirsch HH et al. Histological patterns of polyomavirus nephropathy: Correlation with graft outcome and viral load. Am J Transplantation 2004; 4:2082–2092.

    Article  Google Scholar 

  32. Trofe J, Cavallo T, First M et al. Polyomavirus in kidney and kidney-pancreas transplantation: A defined protocol for immunosuppression reduction and histologic monitoring. Transplant Proc 2002; 34:1788–1789.

    Article  PubMed  Google Scholar 

  33. Ding R, Medeiros M, Dadhania D et al. Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine. Transplantation 2002; 74:987–994.

    Article  PubMed  CAS  Google Scholar 

  34. Ramos ER, Drachenberg CB, Papadimitriou JC et al. Impact of prospective urine cytology on graft function (GF) for earlier diagnosis of polyoma virus nephropathy. J Am Soc Nephrol 2003; 13:378A (Abstract #561).

    Google Scholar 

  35. Agha I, Brennan DC. BK virus and current immunosuppressive therapy. Graft 2002; 5:S65–S72-.

    Article  Google Scholar 

  36. Drachenberg CB, Papadimitriou JC, Wali R et al. Improved outcome of polyoma virus allograft nephropathy with early biopsy. Transplant Proc 2004; 36:758–759.

    Article  PubMed  CAS  Google Scholar 

  37. Nickeleit V, Hirsch HH, Binet IF et al. Polyomavirus infection of renal allograft recipients: From latent infection to manifest disease. J Am Soc Nephrol 1999; 10:1080–1089.

    PubMed  CAS  Google Scholar 

  38. 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; 342:1309–1315.

    Article  PubMed  CAS  Google Scholar 

  39. Randhawa PS, Khaleel-Ur-Rehman K, Swalsky PA et al. DNA sequencing of viral capsid protein VP-1 region in patients with BK virus interstitial nephritis. Transplantation 2002; 73:1090.

    Article  PubMed  CAS  Google Scholar 

  40. Randhawa PS, Vats A, Zygmunt D et al. Quantitation of viral DNA in renal allograft tissue from patients with BK virus nephropathy. Transplantation 2002; 74:485–488.

    Article  PubMed  CAS  Google Scholar 

  41. Wen MC, Wang CL, Wang M et al. Association of JC virus with tubulointerstitial nephritis in a renal allograft recipient. J Med Virol 2004; 72:675–678.

    Article  PubMed  Google Scholar 

  42. Kazory A, Ducloux D, Chalopin JM et al. The first case of JC virus allograft nephropathy. Transplantation 2003; 76:1653–1655.

    Article  PubMed  Google Scholar 

  43. Hurault de Ligny B, Etienne I, Francois A et al. Polyomavirus-induced acute tubulo-interstitial nephritis in renal allograft recipients. Transplant Proc 2000; 32:2760–2761.

    Article  PubMed  CAS  Google Scholar 

  44. Milstone A, Vilchez RA, Geiger X et al. Polyomavirus simian virus 40 infection associated with nephropathy in a lung-transplant recipient. Transplantation 2004; 77:1019–1024.

    Article  PubMed  Google Scholar 

  45. Baksh FK, Finkelstein SD, Swalsky PA et al. Molecular genotyping of BK and JC viruses in human polyomavirus-associated interstitial nephritis after renal transplantation. Am J Kidney Dis 2001; 38:354–365.

    Article  PubMed  CAS  Google Scholar 

  46. Trofe J, Roy-Chaudhury P, Gordon J et al. Early cessation/avoidance regimens are associated with lower incidence of polyomavirus nephropathy. Am J Transplantation 2003; 3:371 (Abstract).

    Google Scholar 

  47. Hirsch HH, Steiger J, Mihatsch MJ. Immunosuppression and BKV Nephropathy. N Engl J Med 2002; 347:2079–2080.

    Article  Google Scholar 

  48. Comoli P, Basso S, Azzi A et al. Dendritic cells pulsed with polyomavirus BK antigen induce ex vivo polyoma BK virus-specific cytotoxic T-cell lines in seropositive healthy individuals and renal transplant recipients. J Am Soc Nephrol 2003; 14(12):3197–3204.

    Article  PubMed  CAS  Google Scholar 

  49. Ginevri F, Pastorino N, De Santis R et al. Retransplantation after kidney graft loss due to polyoma BK virus nephropathy: Successful outcome without original allograft nephrectomy. Am J Kidney Dis 2003; 42:821–825.

    Article  PubMed  Google Scholar 

  50. Vaz B, Swarup S, Randhawa PS et al. Cytokine gene polymorphism is associated with BK virus nephropathy in renal transplantation. J Am Soc Nephrol 2003; 13:(Abstract) [SA-FC191].

    Google Scholar 

  51. Barri YM, Ahmad I, Ketel BL et al. Polyoma viral infection in renal transplantation: The role of immunosuppressive therapy. Clin Transplant 2001; 15:240–246.

    Article  PubMed  CAS  Google Scholar 

  52. Randhawa P, Zygmunt D, Shapiro R et al. Viral regulatory region sequence variations in kidney tissue obtained from patients with BK virus nephropathy. Kidney Int 2003; 64:743–747.

    Article  PubMed  CAS  Google Scholar 

  53. Helderman JH, Bennett WM, Cibrik DM et al. Immunosuppression: Practice and trends. Am J Transplantation 2003; 3(S4):41–52.

    Article  Google Scholar 

  54. Hodur DM, Mandelbrot D. Immunosuppression and BKV Nephropathy. N Engl J Med 2002; 347:2079.

    Article  PubMed  Google Scholar 

  55. Sachdeva MS, Nada R, Jha V et al. The high incidence of BK polyoma virus infection among renal transplant recipients in India. Transplantation 2004; 77:429–431.

    Article  PubMed  Google Scholar 

  56. Wong W, Hirsch HH, Pascual MDMT et al. BK virus replication in kidney transplant recipients who received thymoglobulin induction. J Am Soc Nephrol 2003; 14:(Abstract) [SU-PO539].

    Google Scholar 

  57. Atencio IA, 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 regeneration. J Virol 1993; 67:1424–1432.

    PubMed  CAS  Google Scholar 

  58. Dadhania D, Muthukumar T, Snopkowski C et al. Epidemiology of BK virus replication in renal allograft recipients and identification of corticosteroid maintenance therapy as an independent risk factor. Am J Transplantation 2004; 4:S198 (Abstract #144).

    Google Scholar 

  59. 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 Transplant 2003; 3:1378–1382.

    Article  PubMed  Google Scholar 

  60. Moens U, Subramaniam N, Johansen B et al. A steroid hormone response unit in the late leader of the noncoding control region of the human polyomavirus BK confers enhanced host cell permissivity. J Virol 1994; 68:2398–2408.

    PubMed  CAS  Google Scholar 

  61. 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; 1:373–381.

    Article  PubMed  CAS  Google Scholar 

  62. Nickeleit V, Steiger J, Mihatsch MJ. BK virus infection after kidney transplantation. Graft 2003; 5:S46–S57.

    Article  Google Scholar 

  63. 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; 15:324–332.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  65. 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; 184:1494–1495.

    Article  PubMed  CAS  Google Scholar 

  66. 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; 183:1669–1672.

    Article  PubMed  CAS  Google Scholar 

  67. Wali R, Drachenberg CB, Hirsch HH et al. Early detection of BK virus-nephropathy in renal allograft recipients and modification of immunosuppressive therapy to combinations with sirolimus and prednisone is associated with a reduction in BK viremia and improvement of allograft function. Transplantation 2004; 78:1069–1073.

    Article  PubMed  CAS  Google Scholar 

  68. Josephson M, Javaid B, Robert H et al. Polyoma nephropathy: Leflunomide blood levels needed for control of this infection. Am J Transplantation 2004; 4:S587 (Abstract #1563).

    Google Scholar 

  69. Brennan DC, Agha I, Bohl DL et al. Incidence of BK with tacrolimus versus cyclosporine and impact of presumptive immunosuppression reduction. Am J Transplant 2005; 5:in press.

    Google Scholar 

  70. Ramos E, Drachenberg CB, Portocarrero M et al. Effects of type of immunosuppression reduction in patients with BK allograft nephropathy. Am J Transplantation. 2003; 561:(Abstract #1596).

    Google Scholar 

  71. Mayr M, Nickeleit V, Hirsch HH et al. Polyomavirus BK nephropathy in a kidney transplant recipeent: Critical Issues of Diagnosis and Management. Am J Kidney Dis 2001; 38:13E.

    Article  Google Scholar 

  72. Al Jedai AH, Honaker MR, Trofe J et al. Renal allograft loss as the result of polyomavirus interstitial nephritis after simultaneous kidney-pancreas transplantation: Results with kidney retransplantation. Transplantation 2003; 75:490–494.

    Article  Google Scholar 

  73. Kadambi PV, Josephson MA, Williams J et al. Treatment of refractory BK virus-associated nephropathy with cidofovir. Am J Transplant 2003; 3:186–191.

    Article  PubMed  Google Scholar 

  74. Vats A, Shapiro R, Randhawa PS et al. BK virus associated nephropathy and cidofovir: Long term experience. Am J Transplantion 2003; 190:(Abstract #148).

    Google Scholar 

  75. Vats A, Shapiro R, Singh RP et al. Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults. Transplantation 2003; 75:105–112.

    Article  PubMed  CAS  Google Scholar 

  76. Chandraker A, Ali S, Drachenberg C et al. Use of fluorochinolones to treat BK infection in renal transplant recipients. Am J Transplantation 2004; 4:587 (Abstract #1564).

    Google Scholar 

  77. Boucek P, Voska L, Saudek F. Successful retransplantation after renal allograft loss to polyoma virus interstitial nephritis. Transplantation 2002; 74:1478.

    Article  PubMed  Google Scholar 

  78. Poduval RD, Meehan SM, Woodle ES et al. Successful retransplantation after renal allograft loss to polyomavirus interstitial nephritis. Transplantation 2002; 73:1166–1163.

    Article  PubMed  Google Scholar 

  79. Ramos E, Vincenti F, Lu WX et al. Retransplantation in patients with graft loss caused by polyoma virus nephropathy. Transplantation 2004; 77:131–133.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Basel, Basel, Switzerland

    Hans H. Hirsch M.D., M.S. & Juerg Steiger M.D.

  2. University of Maryland School of Medicine, Baltimore, Maryland, USA

    Cinthia B. Drachenberg & Emilio Ramos

Authors
  1. Hans H. Hirsch M.D., M.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cinthia B. Drachenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juerg Steiger M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Emilio Ramos
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Mayo Clinic Transplant Center, Mayo Clinic - College of Medicine, Jacksonville, Florida, USA

    Nasimul Ahsan M.D., FACP

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Eurekah.com and Springer Science+Business Media

About this chapter

Cite this chapter

Hirsch, H.H., Drachenberg, C.B., Steiger, J., Ramos, E. (2006). Polyomavirus-Associated Nephropathy in Renal Transplantation. 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_11

Download citation

Publish with us

Policies and ethics

Search

Navigation