J Korean Soc Transplant.  2012 Mar;26(1):23-31. 10.4285/jkstn.2012.26.1.23.

Clinical Manifestations of BK Virus Infection in Kidney Transplant Recipients: A Single Center Experience

• Yoo YS
• Park HS
• Oh SW
• Chae DW
• Lee T

• KMID: 1435079
• DOI: http://doi.org/10.4285/jkstn.2012.26.1.23

Abstract

BACKGROUND
BK virus (BKV) has emerged as an important cause of graft dysfunction and failure in renal transplant recipients. Reduction of immunosuppressive therapy is accepted as the primary strategy for management of BKV infection in renal transplant recipients, a strategy which frequently results in graft dysfunction and failure. Herein, a single center experience of BKV infection in renal transplant recipients is presented with an emphasis on the management of BKV infection.
METHODS
We retrospectively reviewed the medical records of 107 renal transplant recipients who were treated at the outpatient clinic in Seoul National University Bundang Hospital from April 2003 to April 2011. The effects of the modification of immunosuppression on the replication of BKV and graft outcome were analyzed.
RESULTS
Of a total of 35 patient evaluated for BKV infection, 20 tested positive in at least one BK virus test. Decoy cells in urine were detected in 13 of the 20 patients. Of these patients, 7 developed BKV nephropathy. Four out of seven of the BKV nephropathy patients were diagnosed with biopsy, and the other three were diagnosed based on a high titer of BKV replication detected in plasma samples. Despite the reduction in immunosuppression and use of leflunomide in the seven BKV nephropathy patients, two patients suffered deterioration of renal function and one patient lost the graft with progressive renal dysfunction.
CONCLUSIONS
BK virus nephropathy was not an uncommon disease and was a major cause of graft dysfunction or loss. Appropriate modification of immunosuppressive therapy, early in the course of BK nephropathy or before the occurrence of massive replication of BKV, is essential for the protection of renal allografts.

Keyword

BK virus; Viremia; Nephropathy; Immunosuppression reduction

MeSH Terms

Ambulatory Care Facilities
Biopsy
BK Virus
Humans
Immunosuppression
Isoxazoles
Kidney
Medical Records
Plasma
Retrospective Studies
Secondary Prevention
Transplantation, Homologous
Transplants
Viremia
Isoxazoles

Figure

• 

  Fig. 1 BK virus infection management algorithm based on our current practice.

• 

  Fig. 2 Flow diagram depicting clinical outcomes of 20 patients of BK virus infection. Abbreviations: U, urine BK virus DNA PCR; S, serum BK virus DNA PCR; BKVN, BK virus nephropathy.

• 

  Fig. 3 Clinical course of patient 1 (A) and patient 2 (B) who accompanied by concomitant acute rejection. Abbreviations: AR, acute rejection; BKVN, BK virus nephropathy; IVIG, intravenous immunoglobulin; Tac, tacrolimus; MMF, mycophenolate mofetil; ATG, antithymocyte globulin.

Reference

1. El-Zoghby ZM, Stegall MD, Lager DJ, Kremers WK, Amer H, Gloor JM, et al. Identifying specific causes of kidney allograft loss. Am J Transplant. 2009. 9:527–535.

2. Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ, et al. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med. 2002. 347:488–496.

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. 18:1190–1196.

4. Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP, et al. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation. 2005. 79:1277–1286.

5. Hirsch HH. Polyomavirus BK nephropathy: a (re-)emerging complication in renal transplantation. Am J Transplant. 2002. 2:25–30.

6. Binet I, Nickeleit V, Hirsch HH, Prince O, Dalquen P, Gudat F, et al. Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation. 1999. 67:918–922.

7. Brennan DC, Agha I, Bohl DL, Schnitzler MA, Hardinger KL, Lockwood M, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant. 2005. 5:582–594.

8. Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet. 1971. 1:1253–1257.

9. 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.

10. Dei R, Marmo F, Corte D, Sampietro MG, Franceschini E, Urbano P. Age-related changes in the prevalence of precipitating antibodies to BK virus in infants and children. J Med Microbiol. 1982. 15:285–291.

11. Bohl DL, Storch GA, Ryschkewitsch C, Gaudreault-Keener M, Schnitzler MA, Major EO, 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.

12. 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.

13. Gardner SD, MacKenzie EF, Smith C, Porter AA. Prospective study of the human polyomaviruses BK and JC and cytomegalovirus in renal transplant recipients. J Clin Pathol. 1984. 37:578–586.

14. Nickeleit V, Hirsch HH, Zeiler M, Gudat F, Prince O, Thiel G, et al. BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dial Transplant. 2000. 15:324–332.

15. Ramos E, Drachenberg CB, Papadimitriou JC, Hamze O, Fink JC, Klassen DK, et al. Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol. 2002. 13:2145–2151.

16. Barri YM, Ahmad I, Ketel BL, Barone GW, Walker PD, Bonsib SM, et al. Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy. Clin Transplant. 2001. 15:240–246.

17. 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.

18. 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. 22:626–634.

19. 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.

20. Manitpisitkul W, Drachenberg C, Ramos E, Munivenkatappa R, Philosophe B, Klassen D, et al. Maintenance immunosuppressive agents as risk factors for BK virus nephropathy: a case-control study. Transplantation. 2009. 88:83–88.

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

22. Randhawa PS, Demetris AJ. Nephropathy due to polyomavirus type BK. N Engl J Med. 2000. 342:1361–1363.

23. Randhawa P, Vats A, Shapiro R. Monitoring for polyomavirus BK And JC in urine: comparison of quantitative polymerase chain reaction with urine cytology. Transplantation. 2005. 79:984–986.

24. Singh HK, Andreoni KA, Madden V, True K, Detwiler R, Weck K, et al. Presence of urinary Haufen accurately predicts polyomavirus nephropathy. J Am Soc Nephrol. 2009. 20:416–427.

25. Nickeleit V, Klimkait T, Binet IF, Dalquen P, Del Zenero V, Thiel G, 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.

26. Vera-Sempere FJ, Rubio L, Moreno-Baylach MJ, Garcia A, Prieto M, Camanas A, et al. Polymerase chain reaction detection of BK virus and monitoring of BK nephropathy in renal transplant recipients at the University Hospital La Fe. Transplant Proc. 2005. 37:3770–3773.

27. Randhawa P, Ho A, Shapiro R, Vats A, Swalsky P, Finkelstein S, 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.

28. Lefferts JA, Hicks ND, Tsongalis GJ. Evaluation of a BK virus real-time PCR assay designed using novel bioinformatics technology. Exp Mol Pathol. 2010. 89:99–102.

29. Limaye AP, Jerome KR, Kuhr CS, Ferrenberg J, Huang ML, Davis CL, et al. Quantitation of BK virus load in serum for the diagnosis of BK virus-associated nephropathy in renal transplant recipients. J Infect Dis. 2001. 183:1669–1672.

30. Laskin BL, Goebel J. Cost-efficient screening for BK virus in pediatric kidney transplantation: a single-center experience and review of the literature. Pediatr Transplant. 2010. 14:589–595.

31. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009. 9:Suppl 3. S1–S155.

32. Howell DN, Smith SR, Butterly DW, Klassen PS, Krigman HR, Burchette JL Jr, et al. Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients. Transplantation. 1999. 68:1279–1288.

33. Drachenberg C, Hirsch HH, Papadimitriou JC, Mozafari P, Wali R, McKinney JD, et al. Cost efficiency in the prospective diagnosis and follow-up of polyomavirus allograft nephropathy. Transplant Proc. 2004. 36:3028–3031.

34. Ginevri F, Azzi A, Hirsch HH, Basso S, Fontana I, Cioni M, 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.

35. Cosio FG, Amer H, Grande JP, Larson TS, Stegall MD, Griffin MD. Comparison of low versus high tacrolimus levels in kidney transplantation: assessment of efficacy by protocol biopsies. Transplantation. 2007. 83:411–416.

36. Kayler LK, Batal I, Mohanka R, Morgan C, Basu A, Shapiro R, et al. Antirejection treatment in kidney transplant patients with BK viruria. Transplantation. 2008. 86:797–803.

37. Sener A, House AA, Jevnikar AM, Boudville N, McAlister VC, Muirhead N, 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.

38. Johnston O, Jaswal D, Gill JS, Doucette S, Fergusson DA, Knoll GA. Treatment of polyomavirus infection in kidney transplant recipients: a systematic review. Transplantation. 2010. 89:1057–1070.

39. Andrews CA, Shah KV, Daniel RW, Hirsch MS, Rubin RH. A serological investigation of BK virus and JC virus infections in recipients of renal allografts. J Infect Dis. 1988. 158:176–181.

40. Vera-Sempere FJ, Rubio L, Felipe-Ponce V, Garcia A, Sanahuja MJ, Zamora I, et al. Renal donor implication in the origin of BK infection: analysis of genomic viral subtypes. Transplant Proc. 2006. 38:2378–2381.