Commentary on reducing infectious risks: polyoma (BK) virus

Abstract

E ven though it was first identified as a urologic pathogen in the 1970s, BK virus remained relatively obscure until the late 1990s.1,2 Its recent emergence as a threat to allograft longevity coincides with availability of potent immunosuppressive protocols. Initially, BK nephritis was confused with acute rejection, and immunosuppression was intensified. Now, its presence in blood or urine is thought to signify an overimmunosuppressed state, and reducing the dose of immunosuppressant drugs often results in viral clearance even before BK nephritis becomes clinically evident. Study 1 in this section by Ramos and colleagues reports outcomes in 93 patients with BK nephropathy. Graft loss occurred in 28% of patients despite reduction of immunosuppression, and more than 20% of patients experienced acute rejection with dose reduction. Interestingly, going from triple to double therapy, regardless of maintenance drug used with steroids, produced the best overall outcomes. In a smaller study conducted by Rocha and colleagues, patients who underwent transplantation between 1999 and 2000 were analyzed to discover the relationship between treatment of acute rejection and BK nephropathy. The authors concluded that higher tacrolimus levels were associated with increased risk for BK viruria but discontinuation of mycophenolate mofetil resulted in clearance of viruria without graft failure. This finding is consistent with our expanding knowledge regarding the lack of impact of tacrolimus on mycophenolate mofetil pharmacokinetics.3 New approaches are on the horizon. In the third study, Trofe and associates studied the relationship between early steroid cessation/avoidance and polyomavirus BK nephropathy. They determined that steroid avoidance regimens may be associated with substantially less risk of BK viremia and BK nephropathy than standard protocols. As greater longterm experience accrues with these regimens, this benefit may become better defined. In addition, some data from human studies, along with animal data, indicate that pyrimidine antagonists (such as leflunamide) may offer the combined benefits of immunosuppressive and antiviral effects. Obviously, much work in this area remains before substitution of leflunamide (or its analog, FK778) for mycophenolate mofetil can be recommended.