For decades, kidney transplant physicians have had only one real option for managing BK virus: reducing immunosuppression. However, this approach has limitations, including the risk of an acute rejection episode if immunosuppression reduction is too severe. Emerging antiviral therapies are now working their way through clinical trials, offering the hope of additional management options.

A dilemma that physicians face with their patients who undergo a kidney transplant is that enough immunosuppression prevents rejection, but too much allows dormant viruses such as BK virus (also known as BK polyomavirus) to reactivate, predisposing patients to graft dysfunction from BK nephropathy. BK reactivation is a common complication that can occur with kidney transplants and usually indicates excessive immunosuppression. When we reduce immunosuppression too much or for too long, patients can end up with an acute rejection episode, which is equally bad for the graft.

Another way to mismanage BK virus is by not detecting it. Guidelines recommend screening for BK virus, especially in the first year after undergoing a transplant. However, if it is not detected early, patients may be at greater risk of allograft loss.

We must look at the patient as a whole to determine their immunologic risk for rejection. If a patient has a high immunologic risk—perhaps they have had a rejection in the past or they have antibodies to the graft—I would be slower in reducing immunosuppression. If a patient has a low immunologic risk—perhaps they have no antibodies, are older, and/or they have already had other infections—to me, this is a signal that we need to be more aggressive with immunosuppression reduction. A third factor is BK viral load in the blood. If it is increasing quickly or the viral load is very high, this is another reason to be more aggressive.

Immunosuppression reduction remains the primary treatment for BK virus. Several adjunctive agents, including cidofovir, leflunomide, and fluoroquinolones, have been tried for a theoretical antiviral benefit, but none have shown proven clinical benefit, and they are not benign. For example, cidofovir carries a nephrotoxicity risk, and leflunomide can cause drug-induced liver injury. Fluoroquinolones have also failed to demonstrate clinical benefit in randomized trials and are not recommended for BK virus treatment or prophylaxis. The role of mTOR inhibitors remains uncertain.

More recently, there has been more drug development with agents specifically targeting the virus. Monoclonal antibodies are furthest along in development, with 2 phase 2 trials completed and 1 agent, potravitug, moving into a phase 3 trial. This is exciting, but phase 3 data are still needed. Moreover, monoclonal antibodies are administered via infusions, raising questions regarding cost and feasibility.

One drug that is already in use, intravenous immunoglobulin, is typically reserved for severe BK virus cases or when reducing immunosuppression alone has not worked. It is thought to work through passive immunity against BK, although the supporting data are weak, and it is an expensive infusion. Despite this, intravenous immunoglobulin remains a commonly used option, and a study evaluating its benefit is underway.

Vaccination remains an aspirational prevention strategy. We have identified some risk factors for BK viremia and nephropathy, but we cannot at this point identify which specific patients need prophylaxis or vaccination. The approach can also possibly involve vaccinating all patients. However, the vaccine is still in early stages of development.

I think that the ideal situation would be to not have to reduce immunosuppression if BK virus is the only issue a patient is facing. This way, the risk of rejection never enters the picture. However, in reality, immunosuppression reduction is most likely still going to be part of the approach, since BK virus replication is a signal of excessive immunosuppression. Therefore, it is likely going to be a combination of immunosuppression reduction and potential antiviral treatment.