The document discusses BK polyomavirus, which is a double-stranded DNA virus that can cause BK virus nephropathy (BKVN) in transplant recipients. It is transmitted through multiple routes and reactivates due to immunosuppression after transplantation. BKVN diagnosis involves detecting viral DNA in plasma/urine and identifying viral inclusions on allograft biopsy. While prevention is important, no treatment has proven fully effective against established BKVN. Common approaches include decreasing immunosuppression and off-label use of antivirals like cidofovir or IV immunoglobulin.

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

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

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

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

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