| BK virus | |
|---|---|
| Virus classification | |
| Group: | Group I (dsDNA) |
| Family: | Polyomaviridae |
| Genus: | Polyomavirus |
| BK virus | |
|---|---|
| Classification and external resources | |
| MeSH | D027601 |
The BK virus is an incurable member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunocompromised and the immunosuppressed.
Contents |
History
The BK virus was first isolated in 1971 from the urine of a renal transplant patient, initials B.K.[1] 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 or by using a PCR based genotyping approach.
Presentation
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.
The virus then disseminates to the kidneys and urinary tract where it persists for the life of the individual. It is thought that up to 80% of the population contains a latent form of this virus, which remains latent until there is some form of immunosuppression.
Presentation in these individuals is much more severe. Clinical manifestations include renal dysfunction (seen by a progressive rise in serum creatinine), and an abnormal urinalysis consisting of renal tubular cells and inflammatory cells.
Transmission
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 or urine, since infected individuals periodically excrete virus in the urine. A survey of 400 healthy blood donors was reported as showing that 82% were positive for BK virus.[2]
Immunosuppressant-induced susceptibility
In some renal transplant patients, the necessary use of immunosuppressant medications has the side-effect of allowing the virus to replicate within the graft, a disease called BK nephropathy.[3]
It is thought that 1-10% of patients progress to BK virus nephropathy (BKVN) and up to 80% of these patients were reported to lose their grafts. The onset of nephritis can occur in as early as days post-transplant or as late as 5 years.
It is also associated with ureteral stenosis and interstitial nephritis. In bone marrow transplant recipients it is notable as a cause for hemorrhagic cystitis.
Diagnosis
This virus can be diagnosed by BKV blood & urine testing, in addition to carrying out a biopsy in the kidneys. PCR techniques are also carried out to identify the virus.[4]
Treatment
1) Reduction of Immunosuppression Recent surge in BKVN correlates with use of potent immunosuppressant drugs, such as tacrolimus and mycophenolate mofetil (MMF).
• Studies have not shown any correlation between BKVN and a single immunosuppressive agent but rather the overall immunosuppressive load.
Cornerstone of therapy is reduction in immunosupression
• No guidelines or drug levels and doses exist for proper reduction of immunosupressants in BKVN
• Most common methods:
o Withdrawal of MMF or tacrolimus
o Replacement of tacrolimus by cyclosporine
o Overall reduction of immunosuppressive load
o Some cyclosporine trough levels reported to be reduced to 100-150 ng/ml and tacrolimus levels reduced to 3-5 ng/ml
• Retrospective analysis of 67 patients concluded graft survival was similar between reduction and discontinuation of agents.
• Single center study showed renal allografts were preserved in 8/8 individuals managed with reduction in immunosupression while graft loss occurred in 8/12 patients treated with an increase in therapy for what was thought to be organ rejection.
Other therapeutic options include Leflunomide, Cidofovir, IVIG, and the fluoroquinolones. Leflunomide is now generally accepted as the second treatment option behind reduction of immunosuppression.
Leflunomide in BKVN The rationale behind using leflunomide in BKVN comes from its combined immunosuppressive and antiviral properties.
• Two studies consisting of 26 and 17 patients who developed BKVN on a three-drug regimen of tacrolimus, MMF, and steroids had their MMF replaced with leflunomide 20-60mg daily.
o 84 and 88% of patients, respectively had clearance or a progressive reduction in viral load and a stabilization or improvement of graft function7.
• In a study conducted by Teschner et al8. in 2009, 12/13 patients who had their MMF exchanged with leflunomide cleared the virus by 109 days.
• In a case series, there was improvement or stabilization in 23/26 patients with BKVN after switching MMF to leflunomide.
Dosing and Monitoring' There are no dosing guidelines for leflunomide in BKVN. Patient to patient variability has made dosing and monitoring of leflunomide extremely difficult.
• Study of 26 and 17 patients were dosed between 20mg/day and 60mg/day with trough levels of 50-100 mcg/ml.
o Failure was seen in patients with leflunomide plasma levels <40 mcg/ml
• One study of 21patients found that low levels (<40 mcg/ml) and high levels (>40mcg/ml) had similar effects on the rate of viral clearance
o Those with higher levels had more adverse events (hematologic, hepatic)
• In the study by Teschner et al8., dosages and drug concentration showed no correlation with substantial variation from person to person.
In the Teschner8 study, low drug concentrations were associated with decrease in viral load.
• This makes it difficult to determine whether or not reduction of viral load or addition of leflunomide was the cause for viral clearance.
Other Treatment Options
• Quinolone Antibiotics
o Ciprofloxaxin was shown to significantly lower viral loads but no data on survival and graft loss.
• IVIG
o Has use in the treatment of infection and allograft rejection – hard to distinguish
• Cidofovir
o Limited data, highly nephrotoxic
References
- ^ Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet. 1971 Jun 19;1(7712):1253-7.
- ^ Egli A, Infanti L, Dumoulin A, et al. (2009). "Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors". J Infect Dis 199 (6): 837–846. doi:.
- ^ Fishman J. BK Virus Nephropathy — Polyomavirus Adding Insult to Injury. New England Journal of Medicine 15 Aug, 2002
- ^ Bista BR, Ishwad C, Wadowsky RM, Manna P, Randhawa PS, Gupta G, Adhikari M, Tyagi R, Gasper G, Vats A. Development of Loop Mediated Isothermal Amplification Assay for Rapid Detection of BK virus. Journal of Clinical Microbiology. 2007 May;45(5):1581-7. PMID 17314224
External links
- 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.
- Katrien Blanckaert and An S. De Vriese, 2006. Nephrology Dialysis Transplantation, journal of the European Renal Association and the European Dialysis and Transplant Association
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