BK virus

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The BK virus is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon.

The BK virus was first recognized from a renal transplant patient. This BK virus is similar to another virus called the JCV since their genome sequence share 75% homology. Both of these viruses can be identified and differentiated from each other by carrying out serological tests using specific antibodies.

The BK virus rarely causes disease since many people who are infected with this virus are asymptomatic. If symptoms do appear then many of them will be mild such as having a respiratory infection or a fever. These are known as the primary infections. Latent infections can occur in the kidneys and sometimes in the brain. A latent infection occurs when the virus becomes reactivated. However it is not known how this virus is transmitted. It is known however that the virus is spread from person to person and not from an animal source. It has been suggested that this virus may be transmitted through respiratory fluids.

Clinically, BK virus becomes relevant in immunocompromised patients. It is notable as a cause for hemorrhagic cystitis in bone marrow transplant recipients. In renal transplant patients, it is associated with ureteral stenosis and interstitial nephritis. In addition, the presence of BK polyoma in the bladder is statistically linked to the development of bladder carcinoma.

This virus can be diagnosed by carrying out a biopsy in the kidneys. PCR techniques and LAMP (Loop mediated isothermal amplification) can also be carried out to identify the virus. Renal transplant patients infected with this virus can be treated by using cidofovir which is an antiviral drug. Cidofovir is a nucleotide analogue that has the ability to interfere with the action of the BK virus. It is known to have treated individuals with a renal transplant that were infected with this virus.

Treatment

• BK virus treatment

• 1. Immunosuppression should be reduced in kidney transplant patients with definitive polyomavirus associated nephropathy.

• Immunosuppressant drugs

• Preferred regimen (1): Tacrolimus trough levels are commonly targeted to < 6 ng/mL,
• Preferred regimen (2): Cyclosporine trough levels to < 150 ng/mL ,
• Preferred regimen (3): Sirolimus trough levels of < 6 ng/mL, and
• Preferred regimen (4): Mycophenolate mofetil daily dose equivalents of ≤ 1000 mg.
• Note (1): Lower calcineurin inhibitor levels, that is targeting trough levels for Tacrolimus of 3 ng/mL and Cyclosporine of 100 ng/mL may be considered as a first step.
• Note (2): Additional strategies have been switching from Tacrolimus to low-dose Cyclosporine or switching from Mycophenolic acid to Leflunomide, to low-dose Sirolimus, or from calcineurin inhibitor to low-dose Sirolimus.
• Note (3): Immunosuppression is further adapted according to the course of serum creatinine concentration and the plasma viral loads, but responses may require several weeks.

• 2. In patients with sustained high-level plasma BK virus load despite adequately reduced immunosuppression, the adjunctive use of agents with antiviral activity may be considered

• Preferred regimen (1): Cidofovir 0.25 mg/kg-1.0 mg/kg IV at 1–3 weekly intervals, without Probenecid 1 mg/kg, administered weekly as a slow IV infusion after hydration, for up to 10 weeks.
• Preferred regimen (2): Loading dose of Leflunomide 100 mg PO for 5 days, followed by an initial maintenance dose of Leflunomide 40 mg PO.
• Note: Leflunomide is orally administered as a replacement for discontinued Mycophenolic acid.
• Preferred regimen (3): Intravenous immunoglobulins (IVIG) 0.2 g/kg-2.0 g/kg in conjunction with reduced immunosuppression.
• Preferred regimen (4): Fluoroquinolones may inhibit BKV replication.
• Note (1): Acute rejection following reduced immunosuppression for presumptive or definitive polyomavirus associated nephropathy should be treated according to standard protocols.
• Note (2): Anti-rejection treatment administered in patients with a history of BK virus replication with or without polyomavirus associated nephropathy should be accompanied by at least bi-weekly monitoring of the urine and plasma viral load.

Prevention and prophylaxis

• Kidney transplant recipients should be screened for BKV replication to identify patients at increased risk of polyomavirus associated nephropathy.
• Retransplantation can be considered for patients after loss of a first kidney allograft due to polyomavirus associated nephropathy, but frequent screening for BK virus replication is recommended

References

• Overview of the BK virus
• MicrobiologyBytes: Polyomaviruses
• Reploeg, MD., Storch, GA., Clifford, DB., BK virus: A clinical review
• Blackwell Munksgaard, 2004. BK virus. American Journal of Transplantation.