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Primer: histopathology of polyomavirus-associated nephropathy in renal allografts

Nature Clinical Practice Nephrology volume 2, pages 631–636 (2006)Cite this article

Abstract

The BK polyomavirus exhibits tropism for the renal tubular epithelium, where it establishes latent infection. Vigorous immunosuppression of renal allograft recipients can lead to reactivation of the infection and the development of polyomavirus-associated nephropathy (PVAN). Clinically, gradually decreasing renal function, viremia and viruria are observed several months after transplantation; allograft failure occurs in 1–10% of patients. Definitive diagnosis requires an allograft biopsy. Histologically, viral replication results in tubular epithelial cell enlargement, karyomegaly and nuclear inclusion bodies. The cytopathic changes are often associated with lysis of tubular epithelial cells, denudation of the basement membrane and an interstitial inflammatory response. The involvement is multifocal; distal nephron segments are more severely affected than proximal segments. Changes observed during light microscopy are suggestive but not pathognomonic for PVAN, and the diagnosis must be confirmed by adjunct studies. Adjunct studies consist of immunohistochemistry on paraffin sections using an antibody to the SV40 large T antigen, or electron microscopy of infected tubular epithelial cells (virions 40 nm in diameter). PVAN manifests in three histologic patterns: pattern A, viral cytopathic changes with no or only minimal inflammation; pattern B, cytopathic and cytolytic lesions with interstitial inflammation; or pattern C, predominantly interstitial fibrosis and tubular atrophy, with variable cytopathic and inflammatory changes. These patterns correlate with clinical outcomes.

Key Points

  • The incidence of polyomavirus-associated nephropathy (PVAN) of renal allografts has increased since the introduction of new-generation immunosuppressive regimens

  • PVAN is caused by the ubiquitous BK virus, which establishes latent infection in urothelium and renal tubular epithelium; latent BK virus can be reactivated by immunosuppression

  • Diagnosis of PVAN requires renal biopsy; histopathological features include enlargement of tubular epithelial cells and development of nuclear inclusion bodies therein, and interstitial inflammation

  • PVAN must be distinguished from other types of viral infections, and acute and chronic rejection

  • Minimization of immunosuppression is the mainstay of PVAN management

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Figure 1: Polyomavirus cytopathy with large, pleomorphic tubular epithelial cells (green arrows) and associated mixed interstitial inflammation.
Figure 2: Various types of nuclear inclusions in tubular epithelial cells.
Figure 3: Polyomavirus-induced tubulopathy resembling acute tubular necrosis in a tubular profile.
Figure 4: Ultrastructure of polyomavirus-associated nephropathy.
Figure 5: Severe interstitial mononuclear inflammation and tubulitis (green arrowheads) associated with polyomavirus-associated nephropathy.

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References

  1. Zuckerman AJ et al. (Eds; 2004) Principles and Practice of Clinical Virology, edn 5. Chichester: John Wiley and Sons Ltd

    Book  Google Scholar 

  2. Pappo O et al. (1996) Human polyoma virus infection of renal allografts: histopathologic diagnosis, clinical significance, and literature review. Mod Pathol 9: 105–109

    CAS  PubMed  Google Scholar 

  3. Boldorini R et al. (2005) Kidney and urinary tract polyomavirus infection and distribution: molecular biology investigation of 10 consecutive autopsies. Arch Pathol Lab Med 129: 69–73

    PubMed  Google Scholar 

  4. Randhawa P et al. (2005) A comparative study of BK and JC virus infections in organ transplant recipients. J Med Virol 77: 238–243

    Article  PubMed  Google Scholar 

  5. Kazory A et al. (2003) The first case of JC virus allograft nephropathy. Transplantation 76: 1653–1655

    Article  PubMed  Google Scholar 

  6. Howell DN et al. (1999) Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients. Transplantation 68: 1279–1288

    Article  CAS  PubMed  Google Scholar 

  7. Coleman DV et al. (1978) Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients. J Clin Pathol 31: 338–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ramos E et al. (2002) BK virus nephropathy diagnosis and treatment: experience at the University of Maryland Renal Transplant Program. Clin Transplant 13: 143–153

    Google Scholar 

  9. Binet I et al. (1999) Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation 67: 918–922

    Article  CAS  PubMed  Google Scholar 

  10. Humar A (2006) Reactivation of viruses in solid organ transplant patients receiving cytomegalovirus prophylaxis. Transplantation 27 (Suppl): S9–S14

    Article  Google Scholar 

  11. Drachenberg CB et al. (2003) BK polyoma virus allograft nephropathy: ultrastructural features from viral cell entry to lysis. Am J Transplant 3: 1383–1392

    Article  PubMed  Google Scholar 

  12. Drachenberg CB et al. (2005) Polyomavirus disease in renal transplantation: review of pathological findings and diagnostic methods. Hum Pathol 36: 1245–1255

    Article  CAS  PubMed  Google Scholar 

  13. Namba Y et al. (2005) Prevalence, characteristics, and outcome of BK virus nephropathy in Japanese renal transplant patients: analysis in protocol and episode biopsies. Clin Transplant 19: 97–101

    Article  PubMed  Google Scholar 

  14. Mengel M et al. (2003) Incidence of polyomavirus-nephropathy in renal allografts: influence of modern immunosuppressive drugs. Nephrol Dial Transplant 18: 1190–1196

    Article  CAS  PubMed  Google Scholar 

  15. Bressollette-Bodin C et al. (2005) A prospective longitudinal study of BK virus infection in 104 renal transplant recipients. Am J Transplant 5: 1926–1933

    Article  CAS  PubMed  Google Scholar 

  16. Nickeleit V et al. (2003) Polyomavirus nephropathy: morphology, pathophysiology, and clinical management. Curr Opin Nephrol Hypertens 12: 599–605

    Article  PubMed  Google Scholar 

  17. Hirsch HH et al. (2005) Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation 79: 1277–1286

    Article  PubMed  Google Scholar 

  18. Trofe J et al. (2006) Polyomavirus-associated nephropathy: update of clinical management in kidney transplant patients. Transplant Infect Dis 8: 76–85

    Article  CAS  Google Scholar 

  19. Josephson MA et al. (2006) Polyomavirus-associated nephropathy: update on antiviral strategies. Transplant Infect Dis 8: 95–101

    Article  CAS  Google Scholar 

  20. Boldorini R et al. (2005) Periodic assessment of urine and serum by cytology and molecular biology as a diagnostic tool for BK virus nephropathy in renal transplant patients. Acta Cytol 49: 235–243

    Article  PubMed  Google Scholar 

  21. Vera-Sempere FJ et al. (2005) Polymerase chain reaction detection of BK virus and monitoring of BK nephropathy in renal transplant recipients at the University Hospital La Fe. Transplant Proc 37: 3770–3773

    Article  CAS  PubMed  Google Scholar 

  22. Ramos E et al. (2004) Retransplantation in patients with graft loss caused by polyoma virus nephropathy. Transplantation 77: 131–133

    Article  PubMed  Google Scholar 

  23. Womer KL et al. (2006) Preemptive retransplantation for BK virus nephropathy: successful outcome despite active viremia. Am J Transplant 6: 7–9

    Article  Google Scholar 

  24. Nickeleit V et al. (2000) BK-virus nephropathy in renal transplants—tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dial Transplant 15: 324–332

    Article  CAS  PubMed  Google Scholar 

  25. Nickeleit V et al. (1999) Polyomavirus infection of renal allograft recipients: from latent infection to manifest disease. J Am Soc Nephrol 10: 1080–1089

    CAS  PubMed  Google Scholar 

  26. Ahuja M et al. (2001) Polyoma virus infection after renal transplantation: use of immunostaining as a guide to diagnosis. Transplantation 71: 896–899

    Article  CAS  PubMed  Google Scholar 

  27. Celik B et al. (2004) Glomerular changes in BK virus nephropathy. Hum Pathol 35: 367–370

    Article  PubMed  Google Scholar 

  28. Nickeleit V and Mihatsch MJ (2005) Histologic changes in polyomavirus allograft nephropathy. In Updates in Nephropathology and Transplantation; Proceedings of the Nephropathology Pre-congress Meeting of the 20th European Congress of Pathology; Paris, 36–40 (Eds Vizjak A et al.) Ljubljana: Institute of Pathology, University of Ljubljana

    Google Scholar 

  29. Gaber LW et al. (2006) Clinical utility of histological features of polyomavirus allograft nephropathy. Transplantation 82: 196–204

    Article  PubMed  Google Scholar 

  30. Racusen LC et al. (2003) Antibody mediated rejection criteria—an addition to the Banff '97 classification of renal allograft rejection. Am J Transplant 3: 1–7

    Article  Google Scholar 

  31. Solez K et al. (1993) International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int 44: 411–422

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The nephropathologic activities of B Ivanyi are supported by the Hungarian Scientific Research Fund (OTKA) via grant T-038271.

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Authors and Affiliations

  1. Glasgow School of Pathology, Glasgow, UK

    Peter Liptak

  2. Department of Pathology at the University of Szeged, Szeged, Hungary

    Eva Kemeny & Bela Ivanyi

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  1. Peter Liptak
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  2. Eva Kemeny
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  3. Bela Ivanyi
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Correspondence to Bela Ivanyi.

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Liptak, P., Kemeny, E. & Ivanyi, B. Primer: histopathology of polyomavirus-associated nephropathy in renal allografts. Nat Rev Nephrol 2, 631–636 (2006). https://doi.org/10.1038/ncpneph0319

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