Polyomavirus BK Replication in De Novo Kidney Transplant Patients Receiving Tacrolimus or Cyclosporine: A Prospective, Randomized, Multicenter Study

Abstract

Polyomavirus BK (BKV)-associated nephropathy causes premature kidney transplant (KT) failure. BKV viruria and viremia are biomarkers of disease progression, but associated risk factors are controversial. A total of 682 KT patients receiving basiliximab, mycophenolic acid (MPA), corticosteroids were randomized 1:1 to cyclosporine (CsA) or tacrolimus (Tac). Risk factors were analyzed in 629 (92.2%) patients having at least 2 BKV measurements until month 12 posttransplant. Univariate analysis associated CsA-MPA with lower rates of viremia than Tac-MPA at month 6 (10.6% vs. 16.3%, p = 0.048) and 12 (4.8% vs. 12.1%, p = 0.004) and lower plasma BKV loads at month 12 (3.9 vs. 5.1 log(10) copies/mL; p = 0.028). In multivariate models, CsA-MPA remained associated with less viremia than Tac-MPA at month 6 (OR 0.60; 95% CI 0.36-0.99) and month 12 (OR 0.33; 95% CI 0.16-0.68). Viremia at month 6 was also independently associated with higher steroid exposure until month 3 (OR 1.19 per 1 g), and with male gender (OR 2.49) and recipient age (OR 1.14 per 10 years) at month 12. The data suggest a dynamic risk factor evolution of BKV viremia consisting of higher corticosteroids until month 3, Tac-MPA compared to CsA-MPA at month 6 and Tac-MPA, older age, male gender at month 12 posttransplant.

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References 36

1. 1.

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

   Not in our library10.1097/00007890-199901150-00018

2. 2.

   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.

   Not in our library10.1097/00007890-199903270-00022

3. 3.

   Ramos E, Drachenberg CB, Wali R, Hirsch HH. The decade of polyomavirus BK-associated nephropathy: State of affairs. Transplantation. 2009;87:621-630.

   Not in our library10.1097/tp.0b013e318197c17d

4. 4.

   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.

   Not in our library10.1097/01.asn.0000023435.07320.81

5. 5.

   Hirsch HH, Brennan DC, Drachenberg CB, et al. Polyomavirus-associated nephropathy in renal transplantation: Interdisciplinary analyses and recommendations. Transplantation. 2005;79:1277-1286.

   Not in our library10.1097/01.tp.0000156165.83160.09

6. 6.

   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(5 Pt 1):1025-1032.

   Not in our library10.1111/j.1600-6143.2006.01296.x

7. 7.

   Dharnidharka VR, Cherikh WS, Abbott KC. An OPTN analysis of national registry data on treatment of BK virus allograft nephropathy in the United States. Transplantation. 2009;87:1019-1026.

   Not in our library10.1097/tp.0b013e31819cc383

8. 8.

   Schold JD, Rehman S, Kayler 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;22:626-634.

   Not in our library10.1111/j.1432-2277.2009.00842.x

9. 9.

   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.

   Not in our library10.1056/nejmoa020439

10. 10.

    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.

    Not in our library10.1056/nejm200005043421802

11. 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.

    Not in our library10.1111/j.1600-6143.2005.00742.x

12. 12.

    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.

    Not in our library10.1097/01.tp.0000275205.41078.51

13. 13.

    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.

    Not in our library10.1111/j.1600-6143.2007.01984.x

14. 14.

    Schaub S, Hirsch HH, Dickenmann M, et al. Reducing immunosuppression preserves allograft function in presumptive and definitive polyomavirus-associated nephropathy. Am J Transplant. 2010;10:2615-2623.

    Not in our library10.1111/j.1600-6143.2010.03310.x

15. 15.

    Kasiske BLZM, Craig JC, Ekberg H, KDIGO clinical practice guideline for the care of kidney transplant recipients, et al. Am J Transplant. 2009;9(Suppl 3):S1-S155.

    Not in our library10.1111/j.1600-6143.2009.02834.x

16. 16.

    Hirsch HH, Randhawa P. BK virus in solid organ transplant recipients. Am J Transplant. 2009;9(Suppl 4):S136-S146.

    Not in our library10.1111/j.1600-6143.2009.02904.x

17. 17.

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

    Not in our library10.1016/s1473-3099(03)00770-9

18. 18.

    Egli A, Infanti L, Dumoulin A, et al. Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. J Infect Dis. 2009;199:837-846.

    Not in our library10.1086/597126

19. 19.

    Meier-Kriesche HU, Li S, Gruessner RW, et al. Immunosuppression: Evolution in practice and trends, 1994–2004. Am J Transplant. 2006;6(5 Pt 2):1111-1131.

    Not in our library10.1111/j.1600-6143.2006.01270.x

20. 20.

    Manitpisitkul W, Drachenberg C, Ramos E, et al. Maintenance immunosuppressive agents as risk factors for BK virus nephropathy: A case–control study. Transplantation. 2009;88:83-88.

    Not in our library10.1097/tp.0b013e3181aa8d93

21. 21.

    Ramos E, Drachenberg CB, Portocarrero M, et al. BK virus nephropathy diagnosis and treatment: Experience at the University of Maryland Renal Transplant Program. Clin Transplant. 2002;143-153.

    Not in our library

22. 22.

    Vincenti F, Friman S, Scheuermann E, et al. Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus. Am J Transplant. 2007;7:1506-1514.

    Not in our library10.1111/j.1600-6143.2007.01749.x

23. 23.

    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.

    Not in our library10.1086/324425

24. 24.

    Funk GA, Gosert R, Comoli P, Ginevri F, Hirsch HH. Polyomavirus BK replication dynamics in vivo and in silico to predict cytopathology and viral clearance in kidney transplants. Am J Transplant. 2008;8:2368-2377.

    Not in our library10.1111/j.1600-6143.2008.02402.x

25. 25.

    Dadhania D, Snopkowski C, Ding R, et al. Epidemiology of BK virus in renal allograft recipients: Independent risk factors for BK virus replication. Transplantation. 2008;86:521-528.

    Not in our library10.1097/tp.0b013e31817c6447

26. 26.

    Gosert R, Rinaldo CH, Funk GA, et al. Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology. J Exp Med. 2008;205:841-852.

    Not in our library10.1084/jem.20072097

27. 27.

    Khamash HA, Wadei HM, Mahale AS, et al. Polyomavirus-associated nephropathy risk in kidney transplants: The influence of recipient age and donor gender. Kidney Int. 2007;71:1302-1309.

    Not in our library10.1038/sj.ki.5002247

28. 28.

    Arns W, Breuer S, Choudhury S, et al. Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil. Clin Transplant. 2005;19:199-206.

    Not in our library10.1111/j.1399-0012.2004.00318.x

29. 29.

    Koukoulaki M, Grispou E, Pistolas D, et al. Prospective monitoring of BK virus replication in renal transplant recipients. Transpl Infect Dis. 2009;11:1-10.

    Not in our library10.1111/j.1399-3062.2008.00342.x

30. 30.

    Funk GA, Steiger J, Hirsch HH. Rapid dynamics of polyomavirus type BK in renal transplant recipients. J Infect Dis. 2006;193:80-87.

    Not in our library10.1086/498530

31. 31.

    Li YJ, Weng CH, Lai WC, et al. A suppressive effect of cyclosporine A on replication and noncoding control region activation of polyomavirus BK virus. Transplantation. 2010;89:299-306.

    Not in our library10.1097/tp.0b013e3181c9b51c

32. 32.

    Acott PD, O'Regan PA, Lee SH, Crocker JF. In vitro effect of cyclosporin A on primary and chronic BK polyoma virus infection in Vero E6 cells. Transpl Infect Dis. 2008;10:385-390.

    Not in our library10.1111/j.1399-3062.2008.00330.x

33. 33.

    Acott P, O'Regan PA, Crocker JF. Suppression of early and chronic BK polyoma virus replication by mycophenolic acid in Vero cells. Transpl Int. 2009;22:225-231.

    Not in our library10.1111/j.1432-2277.2008.00766.x

34. 34.

    Hirsch HH, Min L, Wernli M. Polyomavirus BK (BKV) replication in renal tubular epithelial cells is inhibited by mTOR inhibitors, but activated by tacrolimus in a pathway involving the FKBP12 (Abstract #497; Accepted for Oral Presentation at the 11th ATC 2011). Am J Transplant. 2011;11-179.

    Not in our library

35. 35.

    Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med. 1998;338:1741-1751.

    Not in our library10.1056/nejm199806113382407

36. 36.

    Comoli P, Hirsch HH, Ginevri F. Cellular immune responses to BK virus. Curr Opin Organ Transplant. 2008;13:569-574.

    Not in our library10.1097/mot.0b013e3283186b93

Cited by papers we hold 1

• Total nephroureterocystectomy and urethrectomy due to urothelial carcinoma associated with the BK polyomavirus infection after kidney transplantation: a case report with literature review · 2020
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