Child Kidney Dis.  2022 May;26(1):11-17. 10.3339/ckd.22.029.

BK polyomavirus-associated nephropathy

• Ahn YH
• Kang HG

• KMID: 2531929
• DOI: http://doi.org/10.3339/ckd.22.029

Abstract

BK polyomavirus (BKPyV) is a ubiquitous virus residing in the kidney tubules and is clinically significant only in immunocompromised patients. In clinical practice, BKPyV is a causative pathogen of BKPyV associated nephropathy (BKVAN) in kidney allograft recipients or hemorrhagic cystitis of hematopoietic stem cell transplant recipients. Currently, there is no effective treatment for BKVAN; therefore, careful monitoring and prudent modification of immunosuppression are necessary to prevent BKVAN. In this article, the epidemiology, pathophysiology, and current management strategies for BKVAN are reviewed.

Keyword

BK polyomavirus; BKVAN; Immunosuppression; Kidney allograft

Figure

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  Fig. 1. Monitoring and management strategy for BK polyomavirus (BKPyV)-associated nephropathy (BKVAN). HPF, high-power field; VL, viral load; EM, electron microscopy; PyV, polyomavirus; PyVAN, polyomavirus-associate nephropathy; AST-IDCOP, American Society of Transplantation Infectious Diseases Community of Practice; Tac, tacrolimus; CsA, cyclosporine-A; MPA, mycophenolic acid or equivalent; mTOR, mammalian target of rapamycin; IVIG, intravenous immunoglobulin. a)Allograft biopsy should be considered in patients with baseline allograft function, if concurrent (subclinical) acute rejection is likely; b)If decline in plasma BKPyV-DNAemia is <1 log10 copies/mL in <4 weeks, further immunosuppression is required. Reuse from Hirsch et al. Clin Transplant [7] with permission from John Wiley and Sons.

Reference

References

1. Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet. 1971; 1:1253–7.

2. Hurdiss DL, Frank M, Snowden JS, Macdonald A, Ranson NA. The structure of an infectious human polyomavirus and its interactions with cellular receptors. Structure. 2018; 26:839–47.

3. Mengel M, Marwedel M, Radermacher J, Eden G, Schwarz A, Haller H, et al. Incidence of polyomavirus-nephropathy in renal allografts: influence of modern immunosuppressive drugs. Nephrol Dial Transplant. 2003; 18:1190–6.

4. Patel H, Rodig N, Agrawal N, Cardarelli F. Incidence and risk factors of kidney allograft loss due to BK nephropathy in the pediatric population: a retrospective analysis of the UNOS/OPTN database. Pediatr Transplant. 2021; 25:e13927.

5. Cho MH. Monitoring BK virus infection in pediatric kidney transplant recipients. Korean J Pediatr. 2019; 62:414–5.

6. Myint TM, Chong C, Wyld M, Nankivell B, Kable K, Wong G. Polyoma BK virus in kidney transplant recipients: screening, monitoring, and management. Transplantation. 2022; 106:e76–89.

7. Hirsch HH, Randhawa PS; AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33:e13528.

8. Bohl DL, Brennan DC. BK virus nephropathy and kidney transplantation. Clin J Am Soc Nephrol. 2007; 2 Suppl 1:S36–46.

9. Vanichanan J, Udomkarnjananun S, Avihingsanon Y, Jutivorakool K. Common viral infections in kidney transplant recipients. Kidney Res Clin Pract. 2018; 37:323–37.

10. Kwon Y, Kim JY, Lee Y, Cho H. Clinical manifestations of BK virus infection in pediatric kidney transplant patients. Korean J Pediatr. 2019; 62:422–7.

11. Lee YH, Kang HG. Pediatric kidney transplantation. Child Kidney Dis. 2021; 25:8–13.

12. Schold JD, Rehman S, Kayle LK, Magliocca J, Srinivas TR, Meier-Kriesche HU. Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States. Transpl Int. 2009; 22:626–34.

13. Demey B, Tinez C, Francois C, Helle F, Choukroun G, Duverlie G, et al. Risk factors for BK virus viremia and nephropathy after kidney transplantation: a systematic review. J Clin Virol. 2018; 109:6–12.

14. Ducharme-Smith A, Katz BZ, Bobrowski AE, Backer CL, Pahl E. BK polyomavirus infection in pediatric heart transplant recipients: a prospective study. Pediatr Transplant. 2017; 21:e12830.

15. Dufek S, Haitel A, Muller-Sacherer T, Aufricht C. Duct Bellini carcinoma in association with BK virus nephropathy after lung transplantation. J Heart Lung Transplant. 2013; 32:378–9.

16. Bedi A, Miller CB, Hanson JL, Goodman S, Ambinder RF, Charache P, et al. Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation. J Clin Oncol. 1995; 13:1103–9.

17. Cesaro S, Dalianis T, Hanssen Rinaldo C, Koskenvuo M, Pegoraro A, Einsele H, et al. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients. J Antimicrob Chemother. 2018; 73:12–21.

18. Ruderfer D, Wu M, Wang T, Srivaths PR, Krance RA, Naik S, et al. BK virus epidemiology, risk factors, and clinical outcomes: an analysis of hematopoietic stem cell transplant patients at Texas Children's Hospital. J Pediatric Infect Dis Soc. 2021; 10:492–501.

19. Laskin BL, Denburg MR, Furth SL, Moatz T, Altrich M, Kleiboeker S, et al. The natural history of BK polyomavirus and the host immune response after stem cell transplantation. Clin Infect Dis. 2020; 71:3044–54.

20. Helle F, Brochot E, Handala L, Martin E, Castelain S, Francois C, et al. Biology of the BKPyV: an update. Viruses. 2017; 9:327.

21. Sawinski D, Trofe-Clark J. BK virus nephropathy. Clin J Am Soc Nephrol. 2018; 13:1893–6.

22. Nickeleit V, Singh HK, Randhawa P, Drachenberg CB, Bhatnagar R, Bracamonte E, et al. The Banff Working Group classification of definitive polyomavirus nephropathy: morphologic definitions and clinical correlations. J Am Soc Nephrol. 2018; 29:680–93.

23. Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation. Am J Transplant. 2013; 13 Suppl 4:179–88.

24. Ryu TH, Kim Hy, Oh JS, Kim JK. Combination therapy of low-dose cidofovir and leflunomide in a kidney transplant recipient with BK virus nephropathy: a case report. Korean J Transplant. 2021; 35(Supple 1):S61.

25. Mallat SG, Tanios BY, Itani HS, Lotfi T, McMullan C, Gabardi S, et al. CMV and BKPyV infections in renal transplant recipients receiving an mTOR inhibitor-based regimen versus a CNI-based regimen: a systematic review and meta-analysis of randomized, controlled trials. Clin J Am Soc Nephrol. 2017; 12:1321–36.

26. Ahlenstiel-Grunow T, Pape L. Immunosuppression, BK polyomavirus infections, and BK polyomavirus-specific T cells after pediatric kidney transplantation. Pediatr Nephrol. 2020; 35:625–31.

27. Schneidewind L, Neumann T, Drager DL, Kranz J, Hakenberg OW. Leflunomide in the treatment of BK polyomavirus associated nephropathy in kidney transplanted patients: a systematic review. Transplant Rev (Orlando). 2020; 34:100565.

28. Bernhoff E, Tylden GD, Kjerpeseth LJ, Gutteberg TJ, Hirsch HH, Rinaldo CH. Leflunomide inhibition of BK virus replication in renal tubular epithelial cells. J Virol. 2010; 84:2150–6.

29. Jung YH, Moon KC, Ha JW, Kim SJ, Ha IS, Cheong HI, et al. Leflunomide therapy for BK virus allograft nephropathy after pediatric kidney transplantation. Pediatr Transplant. 2013; 17:E50–4.

30. Patel SJ, Knight RJ, Kuten SA, Graviss EA, Nguyen DT, Moore LW, et al. Ciprofloxacin for BK viremia prophylaxis in kidney transplant recipients: results of a prospective, double-blind, randomized, placebo-controlled trial. Am J Transplant. 2019; 19:1831–7.

31. Hocker B, Schneble L, Murer L, Carraro A, Pape L, Kranz B, et al. Epidemiology of and risk factors for BK polyomavirus replication and nephropathy in pediatric renal transplant recipients: an international CERTAIN registry study. Transplantation. 2019; 103:1224–33.

32. Schmidt T, Adam C, Hirsch HH, Janssen MW, Wolf M, Dirks J, et al. BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication. Am J Transplant. 2014; 14:1334–45.

33. Smith JM, McDonald RA, Finn LS, Healey PJ, Davis CL, Limaye AP. Polyomavirus nephropathy in pediatric kidney transplant recipients. Am J Transplant. 2004; 4:2109–17.

34. Ginevri F, De Santis R, Comoli P, Pastorino N, Rossi C, Botti G, et al. Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches. Transplantation. 2003; 75:1266–70.

35. Miettinen J, Lautenschlager I, Weissbach F, Wernli M, Auvinen E, Mannonen L, et al. BK polyomavirus viremia and antibody responses of pediatric kidney transplant recipients in Finland. Pediatr Transplant. 2019; 23:e13324.