BK Polyoma Virus Dr Goh Ching Yan
BK virus <ul><li>Polyomavirus. </li></ul><ul><li>Ds DNA with 5 –kb genome. </li></ul><ul><li>Genotype I ,II , III , IV. </...
BK virus Mode of transmission <ul><li>Multiple </li></ul><ul><li>Donor kidney </li></ul><ul><li>Feco-oral </li></ul><ul><l...
BK virus -  pathogenesis <ul><li>Lysis of the tubular cells releases BKV into tubules with bare BM </li></ul><ul><li>Virus...
BK virus -  Risk factors <ul><li>Donor-related </li></ul><ul><li>High donor anti-BK Ab  </li></ul><ul><li>High donor BK se...
BK virus -  Risk factors <ul><li>Transplantation-related </li></ul><ul><li>Procurement injury </li></ul><ul><li>Cold ischa...
BK virus <ul><li>Clinical features </li></ul><ul><li>URTI </li></ul><ul><li>Acute cystitis w/wout hematuria </li></ul><ul>...
BK virus Diagnosis & monitoring <ul><li>Serology </li></ul><ul><li>Ab directed against the BKV –common in the general ppn ...
Decoy cells
BK virus Diagnosis & monitoring <ul><li>PCR </li></ul><ul><li>Viral DNA in the plasma (> 10,000 copies/ml) or urine (10,00...
BKV nuclear incusions
Type I: An amorphous ground-glass variant “ Ground-glass” appearance of nucleus
Type II: granular variant surrounded by a “halo”
Type III: a finely granular variant without halo
Type II/III hybrid: Intranuclear  vesicles
Type IV: a vesicular variant with clumped, irregular chromatin
BK virus Diagnosis & monitoring <ul><li>Allograft biopsy </li></ul><ul><li>Characteristic intranuclear viral inclusions </...
Screening Algorithm Clin J Am Soc Nephrol 1: 374–379, 2006
 
BK virus Differential Diagnosis  <ul><li>BKV nephropathy can resemble acute rejection on biopsy, usually unresponsive to s...
BK virus-  treatment <ul><li>Prevention will be a better strategy than treatment of established disease </li></ul><ul><li>...
BK virus-  treatment <ul><li>Cidofovir- nucleotide analogue of cytosine </li></ul><ul><li>Inhibits viral DNA polymerase </...
BK virus-  treatment <ul><li>Esterification of cidofovir with hexadecyloxypropyl, octadecyloethyl or oleyloxyethyl groups ...
 
BK virus-  treatment <ul><li>IV IgG </li></ul><ul><li>High seroprevalence </li></ul><ul><li>May treat rejection + BKVN </l...
BK virus-  treatment <ul><li>Retinoic acid   In-vitro effect </li></ul><ul><li>Leflunomide   MOA unknown,probably not ef...
 
Conclusion <ul><li>BK virus infection occurs commonly & early after transplantation </li></ul><ul><li>The donor Ab titer i...
THANK YOU
 
 
 
 
 
 
 
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Bk Polyoma Virus

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Dr Goh Ching Yan
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Bk Polyoma Virus

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

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