Clinical Information

BK virus (BKV) is a circular, double-stranded DNA virus with an approximately 5 kilobase-size genome in the polyomavirus family, of which 13 members of the family are known, including the JC virus (JCV) and SV40. BKV shares about 75% of its DNA sequence with JCV. Nearly 80% of the adult population worldwide have antibodies to both viruses, indicating previous infection or exposure to these viruses.

Initial infection with BKV is usually acquired in childhood, mostly asymptomatic or manifesting as a mild flu-like illness. After primary infection, BKV establishes latency in the kidney and bladder of the infected individual. In the setting of immunosuppression, the virus reactivates and begins to replicate, triggering renal tubular cell lysis and viruria. As the reactivation progresses, the virus multiplies and crosses into the bloodstream, causing viremia and invading the kidney graft. In patients with kidney transplants, reactivation of BKV typically reaches peak incidence at 3 months post-transplantation with BK viral replication in the kidney graft, causing BKV-associated nephropathy (BKVAN), which manifests as kidney dysfunction that may result in eventual loss of the transplanted kidney. Reactivation of BKV in the bladder can lead to hemorrhagic cystitis. Currently, there are no US Food and Drug Administration-approved antiviral agents or treatments for BKVAN or BKV-associated hemorrhagic cystitis. The main treatment is to decrease the immunosuppression with risk of acute rejection of the kidney graft.

After BK reactivation, the virus is first detectable in the urine, with viremia developing several weeks later. Quantitative BKV DNA in the plasma is the most widely used and preferred test for the laboratory diagnosis of BKVAN and BKV-associated hemorrhagic cystitis, as BKV viremia has higher positive predictive value (50%-60%) than BKV viruria for the diagnosis of BKVAN. Serial monitoring of BKV DNA level in plasma is recommended to guide optimal immunosuppressant dosing regimen. In those with BKVAN, clearance of BK viremia is a sign of resolution of the nephropathy.