BK virus

Polyomavirus

BK virus belongs to the family papovaviridae and genus polyomavirus. It is a small non-enveloped, virus with Circular double-stranded DNA and icosahedral symmetry.

There are 14 species of polyomavirus, of which only a few have been known to cause human disease.

• BK virus - nephropathy, ureteric stenosis in renal transplant patients.

• JC virus - progressive multifocal leukoencephalopathy

• Merkel cell virus -  Merkel cell carcinoma

Other polyomavirus are WU virus, KI virus, NJ virus etc.

Distribution/prevalence

The distribution is worldwide. Most primary infection of BK (and JC virus) occurs in childhood. By the age of 10 years, >90% of children are seropositive.

Transmission

BK virus (and JC) is transmitted via oral and respiratory routes. Direct skin contact has been implicated in Merkel virus transmission.

Primary BK virus infection

Primary BK virus infection occurs in childhood. Most infections are asymptomatic but mild upper respiratory or urinary tract symptoms may occur.

The viraemia following the primary infection carries the virus to other organs where it develops a latent phase. In the case of BK virus is carried to the renal tubular epithelium, urothelium, tonsil etc.

In healthy individuals, asymptomatic viruria may occur in up to 20% of cases (approx 3.5 X10^3 copies/ml). The rate may go up to 60% in immunocompromised patients. Viruria is evidence of virus replication.

BK virus can cause tubulointerstitial nephropathy and ureteral stenosis in renal transplant patients. It can also cause hemorrhagic cystitis in haematopoietic stem cell transplant patients, presenting with frequency, dysuria, hematuria, and urinary obstruction.

The prevalence of BK virus active infection in kidney transplant recipients is 10%. The graft failure rate was >50% with BKVN. With the identification of the BK virus and prompt treatment, the failure rate is decreasing.

The first sign is often a high level of BK viruria and viraemia, without any deterioration of renal allograft function. However, The commonest and usual manifestation is a rising creatinine level. Viruria may precede the viraemia by up to 4 weeks. Sustained viraemia has a higher sensitivity and specificity.

• BK virus-positive donor, BK virus-negative recipient.
  HLA mismatch.
  Female donor; male recipient.
  African-American donor; white recipient.

• High level of immunosuppression,
  Tacrolimus & MMF based immunosuppression;
  Anti-thymocyte globulin (ATG) induction.

• CMV seronegative recipient,
  Prophylactic use of anti-CMV agent - valganciclovir.

• Diabetes,
  unilateral stent,
  cold-ischaemia time.
  Extremes of age for the recipient.

Methods of monitoring

• Urine PCR

• Serum PCR

• Decoy cell

• Haufen (novel method)

• mRNA (novel method)

How different methods compare against each other?

Most infections are in the early stages, peak 1-3 months. It is rare after 2 years.

Screening is preferred using serum quantitative PCR.

Monitor starting at 1-month posttransplant and then monthly plasma screening for the first 6 to 9 months, then every 3 months until 2 years posttransplant. Then yearly until year 5 post-transplant.

Serum PCR >10000 copies/ml (10^4 copies/ml) with evidence of allograft dysfunction should have renal biopsy.
Serum PCR >10000 copies/ml (10^4 copies/ml) for >2 weeks (i.e. persistent) associated with deteriorating renal function could be taken as a presumptive diagnosis of BK virus nephropathy.

Some units may monitor using urine PCR (viruria precede viraemia by approx 4 weeks). However, it must be confirmed by serum PCR.

BKV DNA PCR greater than 10^7 copies/mL may indicate BK nephropathy.

• Reduction of immunosuppression - T cell is important for recovery. Humoral immunity may play some role.
  
  Stepwise 25-50% reduction in antiproliferative agents (mycophenolate/ azathioprine) & celcineurine inhibitors (tacrolimus) an stopping if control not achieved, as per local protocol.

• Other (less effective/limited use) - cidofovir, leflunomide, fluoroquinolones, and intravenous immunoglobulin (IVIG).

Monitoring response

• Serum Creatinine - once/twice per week.

• Serum BK PCR every 2 weeks

• Allograft biopsy at 2 months

• Monitoring the level of immunosuppressive drugs.

Target

• Clearance of viraemia,

• Normalisation of renal function,

• Increase in BKV-specific IgG level