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  • Review Article
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Management of polyomavirus-associated nephropathy in renal transplant recipients

Nature Reviews Nephrology volume 8, pages 390–402 (2012)Cite this article

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Abstract

Polyomavirus-associated nephropathy (PVAN) remains an important infectious complication after renal transplantation, affecting 1–10% of recipients and causing graft loss in approximately 50% of cases. With the lack of effective antiviral therapy, intensive monitoring for BK virus (BKV) using nucleic acid testing or urine cytology—in combination with a reduction of immunosuppressive therapy—is advocated to detect and prevent BKV reactivation and PVAN, respectively. In this Review, new insights into BKV biology and the development of PVAN are discussed. Clinical diagnostic approaches for the detection, surveillance and therapeutic monitoring of BKV are described. In addition, various strategies for reduction of immunosuppressive therapy are reviewed and an evaluation provided of the mechanisms of action and clinical effects of currently used adjuvant medication such as cidofovir, leflunomide, intravenous immunoglobulins and fluoroquinolone antibiotics. Finally, novel compounds and their in vitro actions against BKV are discussed together with future prospects for specific antiviral drug development.

Key Points

  • Polyomavirus-associated nephropathy (PVAN) occurs in 1–10% of renal allograft recipients, predominantly in the first 2 years after transplantation; PVAN causes graft loss in approximately 50% of cases

  • Monthly BK virus (BKV) screening using plasma nucleic acid testing is advocated in the first 3–6 months, then every 3 months until 2 years after transplantation; any unexplained decline in renal function or treatment for acute rejection should prompt additional testing

  • Pre-emptive reduction of immunosuppressive therapy for BKV viremia (sequential/simultaneous lowering of antimetabolite doses by 50% and doses of calcineurin inhibitors and proliferation signal inhibitors by 30–50%) results in viral clearance in 85–95% of cases

  • Failure to achieve BKV plasma clearance through reduction of immunosuppressive therapy alone and/or occurrence of allograft dysfunction should prompt performance of a renal biopsy in order to exclude PVAN

  • For established PVAN, reduction of immunosuppressive therapy alone is associated with a reduction in pooled death-censored graft failure rate to eight per 100 patient-years

  • Adjuvant therapy with low-dose cidofovir or leflunomide can be attempted in individual cases of PVAN where adequate reduction of immunosuppressive therapy alone fails to clear PVAN, but adverse effects should be weighed against the insufficient proof of benefit

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Figure 1: Histological features of PVAN.
Figure 2: Suggested clinical roadmap for the management of BKV reactivation and PVAN.

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Acknowledgements

The author's work is supported in part by Health Resources and Services Administration contract 234-2005-370011C. The content is the responsibility of the author alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The author would like to thank E. Lerut, Department of Morphology and Molecular Pathology, University Hospitals Leuven, Belgium, for providing the microphotographs for Figure 1.

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  1. Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium

    Dirk R. J. Kuypers

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Kuypers, D. Management of polyomavirus-associated nephropathy in renal transplant recipients. Nat Rev Nephrol 8, 390–402 (2012). https://doi.org/10.1038/nrneph.2012.64

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