American Journal of Kidney Diseases
Volume 54, Issue 1 , Pages 131-142 , July 2009

Polyomavirus Nephropathy: A Current Perspective and Clinical Considerations

  • Alexander C. Wiseman, MD

      Affiliations

    • Corresponding Author InformationAddress correspondence to Alexander C. Wiseman, MD, Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, 1635 N Ursula St, AOP 7089, Aurora, CO 80045

Received 15 December 2008 ,Accepted 30 January 2009.

References 

  1. Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (BK) isolated from urine after renal transplantation. Lancet. 1971;1:1253–1257
  2. Purighalla R, Shapiro R, McCauley J, Randhawa P. BK virus infection in a kidney allograft diagnosed by needle biopsy. Am J Kidney Dis. 1995;26:671–673
  3. Randhawa PS, Finkelstein S, Scantlebury V, et al. Human polyoma virus-associated interstitial nephritis in the allograft kidney. Transplantation. 1999;67:103–109
  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
  5. 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
  6. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319:1096–1100
  7. Stolt A, Sasnauskas K, Koskela P, Lehtinen M, Dillner J. Seroepidemiology of the human polyomaviruses. J Gen Virol. 2003;84:1499–1504
  8. Neff RT, Hurst FP, Falta EM, et al. Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation. 2008;86:1474–1478
  9. Hogan TF, Borden EC, McBain JA, Padgett BL, Walker DL. Human polyomavirus infections with JC virus and BK virus in renal transplant patients. Ann Intern Med. 1980;92:373–378
  10. Erard V, Storer B, Corey L, et al. BK virus infection in hematopoietic stem cell transplant recipients: Frequency, risk factors, and association with postengraftment hemorrhagic cystitis. Clin Infect Dis. 2004;39:1861–1865
  11. Brennan DC, Agha I, Bohl DL, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant. 2005;5:582–594
  12. Bressollette-Bodin C, Coste-Burel M, Hourmant M, Sebille V, Andre-Garnier E, Imbert-Marcille BM. A prospective longitudinal study of BK virus infection in 104 renal transplant recipients. Am J Transplant. 2005;5:1926–1933
  13. 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
  14. 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
  15. 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
  16. Hirsch HH. Polyomavirus BK nephropathy: A (re-)emerging complication in renal transplantation. Am J Transplant. 2002;2:25–30
  17. Randhawa P, Ho A, Shapiro R, et al. Correlates of quantitative measurement of BK polyomavirus (BKV) DNA with clinical course of BKV infection in renal transplant patients. J Clin Microbiol. 2004;42:1176–1180
  18. Hymes LC, Warshaw BL. Polyomavirus (BK) in pediatric renal transplants: Evaluation of viremic patients with and without BK associated nephritis. Pediatr Transplant. 2006;10:920–922
  19. Hirsch HH, Brennan DC, Drachenberg CB, et al. Polyomavirus-associated nephropathy in renal transplantation: Interdisciplinary analyses and recommendations. Transplantation. 2005;79:1277–1286
  20. Drachenberg CB, Papadimitriou JC, Ramos E. Histologic versus molecular diagnosis of BK polyomavirus-associated nephropathy: A shifting paradigm?. Clin J Am Soc Nephrol. 2006;1:374–379
  21. Viscount HB, Eid AJ, Espy MJ, et al. Polyomavirus polymerase chain reaction as a surrogate marker of polyomavirus-associated nephropathy. Transplantation. 2007;84:340–345
  22. Hoffman NG, Cook L, Atienza EE, Limaye AP, Jerome KR. Marked variability of BK virus load measurement using quantitative real-time PCR among commonly used assays. J Clin Microbiol. 2008;46:2671–2680
  23. Drachenberg CB, Papadimitriou JC, Hirsch HH, et al. Histological patterns of polyomavirus nephropathy: Correlation with graft outcome and viral load. Am J Transplant. 2004;4:2082–2092
  24. Chan GS, Tsoi HW, Wong SS, et al. BK virus nephropathy due to KOM-3 strain. Am J Kidney Dis. 2009;54:122–126
  25. Drachenberg CB, Hirsch HH, Papadimitriou JC, et al. Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: A prospective evaluation. Transplantation. 2007;84:323–330
  26. Randhawa P, Baksh F, Aoki N, Tschirhart D, Finkelstein S. JC virus infection in allograft kidneys: Analysis by polymerase chain reaction and immunohistochemistry. Transplantation. 2001;71:1300–1303
  27. Kazory A, Ducloux D, Chalopin JM, Angonin R, Fontaniere B, Moret H. The first case of JC virus allograft nephropathy. Transplantation. 2003;76:1653–1655
  28. 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
  29. Polo C, Perez JL, Mielnichuck A, Fedele CG, Niubo J, Tenorio A. Prevalence and patterns of polyomavirus urinary excretion in immunocompetent adults and children. Clin Microbiol Infect. 2004;10:640–644
  30. Eash S, Manley K, Gasparovic M, Querbes W, Atwood WJ. The human polyomaviruses. Cell Mol Life Sci. 2006;63:865–876
  31. 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
  32. Mannon RB, Hoffmann SC, Kampen RL, et al. Molecular evaluation of BK polyomavirus nephropathy. Am J Transplant. 2005;5:2883–2893
  33. Lipshutz GS, Flechner SM, Govani MV, Vincenti F. BK nephropathy in kidney transplant recipients treated with a calcineurin inhibitor-free immunosuppression regimen. Am J Transplant. 2004;4:2132–2134
  34. Randhawa PS, Gupta G, Vats A, Shapiro R, Viscidi RP. Immunoglobulin G, A, and M responses to BK virus in renal transplantation. Clin Vaccine Immunol. 2006;13:1057–1063
  35. Awadalla Y, Randhawa P, Ruppert K, Zeevi A, Duquesnoy RJ. HLA mismatching increases the risk of BK virus nephropathy in renal transplant recipients. Am J Transplant. 2004;4:1691–1696
  36. Smith JM, Dharnidharka VR, Talley L, Martz K, McDonald RA. BK virus nephropathy in pediatric renal transplant recipients: An analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry. Clin J Am Soc Nephrol. 2007;2:1037–1042
  37. 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
  38. Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA, Cohen EP. BK virus nephritis: Risk factors, timing, and outcome in renal transplant recipients. Kidney Int. 2005;68:1834–1839
  39. Bohl DL, Storch GA, Ryschkewitsch C, et al. Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia. Am J Transplant. 2005;5:2213–2221
  40. Ginevri F, Azzi A, Hirsch HH, et al. Prospective monitoring of polyomavirus BK replication and impact of pre-emptive intervention in pediatric kidney recipients. Am J Transplant. 2007;7:2727–2735
  41. Bohl DL, Brennan DC, Ryschkewitsch C, Gaudreault-Keener M, Major EO, Storch GA. BK virus antibody titers and intensity of infections after renal transplantation. J Clin Virol. 2008;43:184–189
  42. Hariharan S, Cohen EP, Vasudev B, et al. BK virus-specific antibodies and BKV DNA in renal transplant recipients with BKV nephritis. Am J Transplant. 2005;5:2719–2724
  43. Randhawa P, Bohl D, Brennan D, et al. Longitudinal analysis of levels of immunoglobulins against BK virus capsid proteins in kidney transplant recipients. Clin Vaccine Immunol. 2008;15:1564–1571
  44. Krymskaya L, Sharma MC, Martinez J, et al. Cross-reactivity of T lymphocytes recognizing a human cytotoxic T-lymphocyte epitope within BK and JC virus VP1 polypeptides. J Virol. 2005;79:11170–11178
  45. Binggeli S, Egli A, Schaub S, et al. Polyomavirus BK-specific cellular immune response to VP1 and large T-antigen in kidney transplant recipients. Am J Transplant. 2007;7:1131–1139
  46. Comoli P, Azzi A, Maccario R, et al. Polyomavirus BK-specific immunity after kidney transplantation. Transplantation. 2004;78:1229–1232
  47. Comoli P, Binggeli S, Ginevri F, Hirsch HH. Polyomavirus-associated nephropathy: update on BK virus-specific immunity. Transpl Infect Dis. 2006;8:86–94
  48. Benavides CA, Pollard VB, Mauiyyedi S, Podder H, Knight R, Kahan BD. BK virus-associated nephropathy in sirolimus-treated renal transplant patients: Incidence, course, and clinical outcomes. Transplantation. 2007;84:83–88
  49. Wadei HM, Rule AD, Lewin M, et al. Kidney transplant function and histological clearance of virus following diagnosis of polyomavirus-associated nephropathy (PVAN). Am J Transplant. 2006;6:1025–1032
  50. Weiss AS, Gralla J, Chan L, Klem P, Wiseman AC. Aggressive immunosuppression minimization reduces graft loss following diagnosis of BK virus-associated nephropathy: A comparison of two reduction strategies. Clin J Am Soc Nephrol. 2008;3:1812–1819
  51. Wali RK, Drachenberg C, Hirsch HH, et al. BK virus-associated nephropathy in renal allograft recipients: Rescue therapy by sirolimus-based immunosuppression. Transplantation. 2004;78:1069–1073
  52. Womer KL, Guerra G, Dibadj K, et al. Immunosuppression reduction for BK virus nephropathy: A case for caution. Transpl Infect Dis. 2007;9:244–248
  53. 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
  54. McGilvray ID, Lajoie G, Humar A, Cattral MS. Polyomavirus infection and acute vascular rejection in a kidney allograft: Coincidence or mimicry?. Am J Transplant. 2003;3:501–504
  55. Drachenberg CB, Papadimitriou JC. Polyomavirus-associated nephropathy: Update in diagnosis. Transpl Infect Dis. 2006;8:68–75
  56. Hussain S, Bresnahan BA, Cohen EP, Hariharan S. Rapid kidney allograft failure in patients with polyoma virus nephritis with prior treatment with antilymphocyte agents. Clin Transplant. 2002;16:43–47
  57. Jahnukainen T, Malehorn D, Sun M, et al. Proteomic analysis of urine in kidney transplant patients with BK virus nephropathy. J Am Soc Nephrol. 2006;17:3248–3256
  58. Celik B, Shapiro R, Vats A, Randhawa PS. Polyomavirus allograft nephropathy: Sequential assessment of histologic viral load, tubulitis, and graft function following changes in immunosuppression. Am J Transplant. 2003;3:1378–1382
  59. 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
  60. Funk GA, Steiger J, Hirsch HH. Rapid dynamics of polyomavirus type BK in renal transplant recipients. J Infect Dis. 2006;193:80–87
  61. Farasati NA, Shapiro R, Vats A, Randhawa P. Effect of leflunomide and cidofovir on replication of BK virus in an in vitro culture system. Transplantation. 2005;79:116–118
  62. De Clercq E. Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. Clin Microbiol Rev. 2003;16:569–596
  63. Bernhoff E, Gutteberg TJ, Sandvik K, Hirsch HH, Rinaldo CH. Cidofovir inhibits polyomavirus BK replication in human renal tubular cells downstream of viral early gene expression. Am J Transplant. 2008;8:1413–1422
  64. Kuypers DR, Vandooren AK, Lerut E, et al. Adjuvant low-dose cidofovir therapy for BK polyomavirus interstitial nephritis in renal transplant recipients. Am J Transplant. 2005;5:1997–2004
  65. Josephson MA, Gillen D, Javaid B, et al. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplantation. 2006;81:704–710
  66. Faguer S, Hirsch HH, Kamar N, et al. Leflunomide treatment for polyomavirus BK-associated nephropathy after kidney transplantation. Transpl Int. 2007;20:962–969
  67. Leca N, Muczynski KA, Jefferson JA, et al. Higher levels of leflunomide are associated with hemolysis and are not superior to lower levels for BK virus clearance in renal transplant patients. Clin J Am Soc Nephrol. 2008;3:829–835
  68. Randhawa PS. Anti-BK virus activity of ciprofloxacin and related antibiotics. Clin Infect Dis. 2005;41:1366–1367author reply, 1367
  69. Leung AY, Chan MT, Yuen KY, et al. Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2005;40:528–537
  70. Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med. 2001;345:747–755
  71. Sener A, House AA, Jevnikar AM, et al. Intravenous immunoglobulin as a treatment for BK virus associated nephropathy: One-year follow-up of renal allograft recipients. Transplantation. 2006;81:117–120
  72. Sharma AP, Moussa M, Casier S, Rehman F, Filler G, Grimmer J. Intravenous immunoglobulin as rescue therapy for BK virus nephropathy. Pediatr Transplant. 2009;13:123–129
  73. Ortiz A, Justo P, Sanz A, et al. Tubular cell apoptosis and cidofovir-induced acute renal failure. Antivir Ther. 2005;10:185–190
  74. Bollee G, Anglicheau D, Loupy A, et al. High-dosage intravenous immunoglobulin-associated macrovacuoles are associated with chronic tubulointerstitial lesion worsening in renal transplant recipients. Clin J Am Soc Nephrol. 2008;3:1461–1468
  75. Vo AA, Cam V, Toyoda M, et al. Safety and adverse events profiles of intravenous gammaglobulin products used for immunomodulation: A single-center experience. Clin J Am Soc Nephrol. 2006;1:844–852
  76. Randhawa P, Brennan DC. BK virus infection in transplant recipients: An overview and update. Am J Transplant. 2006;6:2000–2005
  77. Bansal S, Lucia MS, Wiseman A. A case of polyomavirus-associated nephropathy presenting late after transplantation. Nat Clin Pract Nephrol. 2008;4:283–287
  78. Saad ER, Bresnahan BA, Cohen EP, et al. Successful treatment of BK viremia using reduction in immunosuppression without antiviral therapy. Transplantation. 2008;85:850–854
  79. Almeras C, Foulongne V, Garrigue V, et al. Does reduction in immunosuppression in viremic patients prevent BK virus nephropathy in de novo renal transplant recipients? (A prospective study). Transplantation. 2008;85:1099–1104
  80. Kiberd BA. Screening to prevent polyoma virus nephropathy: A medical decision analysis. Am J Transplant. 2005;5:2410–2416
  81. Sukov WR, Lewin M, Sethi S, Rakowski TA, Lager DJ. BK virus-associated nephropathy in a patient with AIDS. Am J Kidney Dis. 2008;51:e15–e18
  82. Maddirala S, Pitha JV, Cowley BD, Haragsim L. End-stage renal disease due to polyomavirus in a cardiac transplant patient. Nat Clin Pract Nephrol. 2007;3:393–396
  83. Barber CE, Hewlett TJ, Geldenhuys L, Kiberd BA, Acott PD, Hatchette TF. BK virus nephropathy in a heart transplant recipient: Case report and review of the literature. Transpl Infect Dis. 2006;8:113–121
  84. Limaye AP, Smith KD, Cook L, et al. Polyomavirus nephropathy in native kidneys of non-renal transplant recipients. Am J Transplant. 2005;5:614–620
  85. Menahem SA, McDougall KM, Thomson NM, Dowling JP. Native kidney BK nephropathy post cardiac transplantation. Transplantation. 2005;79:259–260
  86. Doucette KE, Pang XL, Jackson K, et al. Prospective monitoring of BK polyomavirus infection early posttransplantation in nonrenal solid organ transplant recipients. Transplantation. 2008;85:1733–1736
  87. Thomas LD, Vilchez RA, White ZS, et al. A prospective longitudinal study of polyomavirus shedding in lung-transplant recipients. J Infect Dis. 2007;195:442–449
  88. Barton TD, Blumberg EA, Doyle A, et al. A prospective cross-sectional study of BK virus infection in non-renal solid organ transplant recipients with chronic renal dysfunction. Transpl Infect Dis. 2006;8:102–107
  89. Atencio IA, Shadan FF, Zhou XJ, Vaziri ND, Villarreal LP. 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
  90. Fishman JA. BK virus nephropathy—Polyomavirus adding insult to injury. N Engl J Med. 2002;347:527–530
  91. Bogdanovic G, Priftakis P, Giraud G, et al. Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation. J Clin Microbiol. 2004;42:5394–5396
  92. Poduval RD, Meehan SM, Woodle ES, et al. Successful retransplantation after renal allograft loss to polyoma virus interstitial nephritis. Transplantation. 2002;73:1166–1169
  93. 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
  94. Ramos E, Vincenti F, Lu WX, et al. Retransplantation in patients with graft loss caused by polyoma virus nephropathy. Transplantation. 2004;77:131–133
  95. 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
  96. Poduval RD, Meehan SM, Woodle ES, et al. Successful retransplantation after renal allograft loss to polyoma virus interstitial nephritis. Transplantation. 2002;73:1166–1169
  97. Hirsch HH, Ramos E. Retransplantation after polyomavirus-associated nephropathy: just do it?. Am J Transplant. 2006;6:7–9
  98. Womer KL, Meier-Kriesche HU, Patton PR, et al. Preemptive retransplantation for BK virus nephropathy: Successful outcome despite active viremia. Am J Transplant. 2006;6:209–213
  99. Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis. 2003;3:611–623

 Originally published online as doi: 10.1053/j.ajkd.2009.01.271 on April 27, 2009.

PII: S0272-6386(09)00504-6

doi: 10.1053/j.ajkd.2009.01.271

American Journal of Kidney Diseases
Volume 54, Issue 1 , Pages 131-142 , July 2009

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