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BK virus infection post renal transplant

BK virus infection post renal transplant. Dr. Introduction. We shall discuss today regarding Polyomavirus infection, replication, and disease in renal transplant recipients. Polyomavirus infection. Polyomavirus infection

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BK virus infection post renal transplant

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  1. BK virus infection post renal transplant Dr.

  2. Introduction • We shall discuss today regarding • Polyomavirus infection, replication, and disease in renal transplant recipients

  3. Polyomavirus infection • Polyomavirus infection • Typically occurs during childhood, with seroprevalence rates of 65% to 90% by the age of 10 years, and is usually asymptomatic • Individuals with altered immunity, however, can experience high-level replication and may present with urine cytology (“decoy” cells) Transplantation Reviews 2008;22:241–51

  4. Nefrologia 2010;30(6):613-7

  5. Polyomavirus infection • BK virus • Named after the first patient in which it was described • Ubiquitous polyomavirus • Acquired in childhood and becomes latent in uroepithelial cells • Reactivation of BK virus occurs in patients in immunosuppressed states, including • After transplantation Transplantation Proceedings 2008;40: S48–51

  6. Polyomavirus infection • Polyomavirus (BK)–associated nephropathy (BKVN) • Now recognized as significant problem in renal transplants that may lead to progressive allograft dysfunction • First recognized in 1999 in adult renal transplant recipients

  7. Polyomavirus infection • In renal transplant recipients, • Polyomavirus-associated nephropathy (PVAN) develops in 5% of patients and leads to graft loss in approximately 50% of cases • Pathogenesis of PVAN characterized by • Persisting high-level polyoma BK virus (BKV) replication in renal tubular epithelial cells, inflammation, and progressive organ failure with tubular atrophy and fibrosis Transplantation Reviews 2008;22:241–51

  8. Polyomavirus infection • Polyoma virus: Renal transplant recipients • Definitive diagnosis requires histopathological assessment, notably to exclude acute rejection • BK viruria: 20% - 40% of renal transplant patients • BK viremia: approx. 12% of patients • Studies have indicated that • BK viremia greater than 10e4/mL is predictive of definitive PVAN, and these patients should be regarded as having “presumptive PVAN,” and • Reduced immunosuppression should be considered Transplantation Reviews 2008;22:241–51

  9. Nefrologia 2010;30(6):613-7

  10. Polyomavirus infection • Screening patients and donors for BK-specific immunoglobulin G antibodies has the potential for clinical relevancy but is not currently recommended until more extensive data are available Transplantation Reviews 2010 ;24: 28–31

  11. Polyomavirus infection • Patients with 107 viral copies/mL of serum can be treated as having “presumptive” BK nephropathy • BK nephropathy develops through • Three stages • Stage A • Few viral inclusion bodies and occasional positive immunohistochemical staining, with an antibody to SV40 large T antigen that cross-reacts with BK large T antigen

  12. Polyomavirus infection • BK nephropathy • Stage B • Fulminant nephropathy shows an inflammatory infiltrate with focal tubulitis, which may mimic acute rejection but includes prominent intranuclear inclusions and T-antigen staining • Stage C • Diffuse interstitial fibrosis and closely resembles chronic allograft nephropathy

  13. Nefrologia 2010;30(6):613-7

  14. Lancet Infect Dis 2003; 3: 611–23

  15. Polyomavirus infection • A variety of factors related to the • Recipient, donor, transplant, or viruses have been proposed as risk factors for PVAN after renal transplantation, including • Use of intense immunosuppression • (often, but not exclusively, comprising triple therapy with tacrolimus-MMF-prednisolone) • Seems likely that both • Potency of immunosuppression and • Agent specific influences may contribute to the risk of BK reactivation and PVAN Transplantation Reviews 2008;22:241–51

  16. Polyomavirus infection • Consistent with the role of T cells to control BK infection, • he use of antithymocyte globulins has been associated with higher risk Clin J Am Soc Nephrol 2007;2:1037, Transplantation 2007;84:83, Nephrol Dial Transplant 2007;22(suppl 8):viii66,

  17. Nefrologia 2010;30(6):613-7

  18. BK viral nephropathy recommendations for prevention and early diagnosis

  19. BK virus infection: Treatment • The treatment of BKVN is unlikely to be satisfactory until safe and effective antiviral drugs are discovered • Hence, there is a lot of current emphasis on the prevention of this distressing complication

  20. BK virus infection: Treatment • Currently, • Reduction of immunosuppression remains the most widely accepted approach to treatment • It is now assumed that • Screening all transplant patients with serial PCR analyses of urine or serum, with • Prompt reduction of immunosuppression when patients initially display viruria or viremia, will • Prevent or reduce the risk for developing BKVN Transplantation Reviews 2010 ;24: 28–31

  21. BK virus infection: Treatment • Antiviral agents used empirically for BKVN include • Cidofovir • Leflunomide, • Quinolone antibiotics, and • Intravenous immunoglobulin • True efficacy of these strategies is unclear because • No randomized control trials have been done, and the • Value of therapy independent of reduction of immunosuppression has not been specifically evaluated Transplantation Reviews 2007;21:77–85

  22. BK virus infection: Treatment • Recent review “Treatment of polyomavirus infection in kidney transplant recipients” data • Pooled results found a death- censored graft loss rate of • 8/100 patient-years for immunosuppression reduction alone and • 8 and 13/100 patient-years for the addition of cidofovir or leflunomide, respectively Transplantation. 2010 May 15;89(9):1057-70.

  23. BK virus infection: Treatment • Recent review “Treatment of polyomavirus infection in kidney transplant recipients” Conclusions • There does not seem to be a graft survival benefit of adding cidofovir or leflunomide to immunosuppression reduction for the management of PVAN • However, the evidence base is poor and highlights the urgent need for adequately powered randomized trials to define the optimal treatment of this important condition Transplantation. 2010 May 15;89(9):1057-70.

  24. BK virus infection: Treatment • It is a medical and an ethical dilemma • Whether retransplantation should be done after a patient loses the renal graft to polyoma nephropathy • Should immunosuppressive therapy be altered? • Is nephroureterectomy of the failed graft necessary? • What is the natural course of the disease after retransplantation? Transplantation Reviews 2007;21:77–85

  25. BK virus infection: Treatment • Retransplantation after polyomavirus- associated nephropathy has been reported in 17 cases • In these cases, recurrence of nephropathy has occurred in 2 patients and viremia alone in a third patient. • For most of these patients, immunosuppression after retransplantation was the same as for the first transplantation • Allograft nephrectomy was performed in 11 of the 15 patients Transplantation Reviews 2007;21:77–85

  26. BK virus infection: Treatment • Also, all 15 patients had reconstituted their BKV-specific immune control, as demonstrated by negative urine cytology pretransplant • Authors conclude that • Retransplantation in patients without active replication is generally safe Transplantation Reviews 2007;21:77–85

  27. BK virus infection: Treatment • Authors conclude that.. • Control of viral replication, allowing enough time to raise sufficient immune response, which usually requires more than 12 weeks of reduced immunosuppression, appears to be a desirable goal before a second transplant is contemplated. • In addition, nephroureterectomy is not necessary when viral replication is absent before retransplantation. Transplantation Reviews 2007;21:77–85

  28. Conclusions • BKV infections remain a significant concern in kidney transplant patients • Intensive viral monitoring and preemptive adjustment of immunosuppression have led to reduction in the incidence of overt viral nephropathy • Nonetheless, approximately 30% of patients in major transplant programs develop viruria and need to be carefully monitored for the possible development of this complication

  29. Conclusions • In those patients who do develop BK Virus induced allograft injury, we do not have reliable antiviral drugs available at this time • Although early diagnosis and prompt therapeutic intervention have reduced rates of overt graft loss to approximately 15%, surviving grafts frequently show progressive decline in graft function

  30. Conclusions • It is likely that long-term low-grade viruria and viremia promote the development of chronic allograft nephropathy • The magnitude of this problem needs to be clarified by future clinical studies.

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