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Bk Polyoma Virus
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  • 1. BK Polyoma Virus Dr Goh Ching Yan
  • 2. BK virus
    • Polyomavirus.
    • Ds DNA with 5 –kb genome.
    • Genotype I ,II , III , IV.
    • First isolated in 1970 from a Sudanese RTx pt with ureteric stricture.
    • BKVN –diagnosed in 1993 at Pittsburgh & published in1996.
  • 3. BK virus Mode of transmission
    • Multiple
    • Donor kidney
    • Feco-oral
    • Transplacental
  • 4. BK virus - pathogenesis
    • Lysis of the tubular cells releases BKV into tubules with bare BM
    • Virus particles can thus leak into intestitium, from where the virus gains access to capillaries, resulting in viremia
    • Somewhere along this pathway, genotype rearrangements may change the virulence characteristics of the virus.
  • 5. BK virus - Risk factors
    • Donor-related
    • High donor anti-BK Ab
    • High donor BK seropositivity
    • Absence of HLA-C7
    • Recepient –related
    • Age, male, caucasian DM, CMV infection, prior renal tubule injury
    • Recepient seronegayive
    • Absence of HLA-C7
  • 6. BK virus - Risk factors
    • Transplantation-related
    • Procurement injury
    • Cold ischaemic time
    • Delayed graft function
  • 7. BK virus
    • Clinical features
    • URTI
    • Acute cystitis w/wout hematuria
    • Latent phase- urogenital tract (kidneys, UB,prostate, cervix, vulva, testis, semen)
    • - hematolymphoid tissues
    • ( tonsils, mononuclear cells)
    • Reactivation - age, pregnancy,DM, immunosupression
    • RTx - (8/52 to 10/12 post –tx ) +/- fever, myalgia, malaise, leukopenia , anemia, thrombocytopenia, renal dysfuncyion, TIN, ureteral stenosis.
    • Rarely- vasculopathy, meningoencephalopathy, retinitis, pneumonitis, hepatitis
  • 8. BK virus Diagnosis & monitoring
    • Serology
    • Ab directed against the BKV –common in the general ppn , not helpful in the diagnosis
    • Viral culture
    • Grow slowly- weeks to months , not readily available
    • Urine cytology
    • Urine shedding of BKV is more prevalent than viremia.
    • BKV infected renal tubular epithelial (decoy-enlarged nucleus with a single large basophilic intranuclear inclusion) cells appear to deteriorate quickly (within minutes), which may limit urine microscopy as a screening tool -not sensitive or specific.
  • 9. Decoy cells
  • 10. BK virus Diagnosis & monitoring
    • PCR
    • Viral DNA in the plasma (> 10,000 copies/ml) or urine (10,000,000copies/ ml)
    • 100% sensitivity, 88% specificity
    • Histology  3 pattrerns
    • A : mild cytopathic/ cytolytic changes with absent /minimal inflammation or fibrosis
    • B : mild/ mod cytopathic/ cytolytic changes asso with patchy /diffuse tubulo-intestitial inflammation and atrophy
    • C : prominent tubular atrophy & intestitial fibrosis
  • 11. BKV nuclear incusions
  • 12. Type I: An amorphous ground-glass variant “ Ground-glass” appearance of nucleus
  • 13. Type II: granular variant surrounded by a “halo”
  • 14. Type III: a finely granular variant without halo
  • 15. Type II/III hybrid: Intranuclear vesicles
  • 16. Type IV: a vesicular variant with clumped, irregular chromatin
  • 17. BK virus Diagnosis & monitoring
    • Allograft biopsy
    • Characteristic intranuclear viral inclusions
    • Positive immunohistochemical staining/ in-situ hybridization of the infected cells
    • Viral particles by EM
  • 18. Screening Algorithm Clin J Am Soc Nephrol 1: 374–379, 2006
  • 19.  
  • 20. BK virus Differential Diagnosis
    • BKV nephropathy can resemble acute rejection on biopsy, usually unresponsive to steroids when treated as rejection.
    • Asso with endarteritis, fibrinoid arterial necrosis, glomerulitis or accumulation of C4d along the peritubular capillaries.
  • 21. BK virus- treatment
    • Prevention will be a better strategy than treatment of established disease
    • Therapeutic recommendation for BKVN are largely based on anecdotal cases & small series
    • Decreased Immunosuppression
  • 22. BK virus- treatment
    • Cidofovir- nucleotide analogue of cytosine
    • Inhibits viral DNA polymerase
    • 5mg/kg IV q2wks * ?wks
    • S/E: nephrotoxicity (ARF, proteinuria)
    • neutropenia
    • Probably not effective (low selectivity)
    De Clercg E. Clin Microbiol Rev 1997;10:674-693 Farasati, Transplantation 2005,79(1):116-118
  • 23. BK virus- treatment
    • Esterification of cidofovir with hexadecyloxypropyl, octadecyloethyl or oleyloxyethyl groups resuls in increase selectivity and bioavailability with less nephrotoxicity
    • A cautiously conducted controlled clinical trial of these compounds in the management of BKVN appears to be warranted.
    • Randhawa P,Farasati N.Antimicrob Agents Chemother 2006;50:1564-1566
  • 24.  
  • 25. BK virus- treatment
    • IV IgG
    • High seroprevalence
    • May treat rejection + BKVN
    • IV 2g/kg over 2-5days in 8 pts
    • 7/8 off dialysis (88%) after a mean follow-up of 15/12.
    Sener A et al Transplantation 2006;81:117-120
  • 26. BK virus- treatment
    • Retinoic acid  In-vitro effect
    • Leflunomide  MOA unknown,probably not effective (low selectivity)
    • Ciprofloxacin
    • Chen Y et al.Oncogen.1999;18:139-148
    • Farasati, Transplantation 2005,79(1):116-118
    • Josephson, MA, Gillen.Transplantation 2006;81:704
    • Leung, AJH,CID 40:528-537,2005
  • 27.  
  • 28. Conclusion
    • BK virus infection occurs commonly & early after transplantation
    • The donor Ab titer is the biggest risk
    • Urine/blood PCR is an excellent screening tool for BKV infection
    • No proven effective treatment exists
  • 29. THANK YOU
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