BK Virus Allograft Nephropathy: Unresolved Issues Complicate Diagnosis and Management

Abstract

BK virus has emerged as an important cause of graft loss in kidney transplant recipients. While surveillance strategies have increased early detection and, consequently, reduced graft loss, achieving a delicate balance in the use of potent immunosuppression remains key to preventing acute rejection and BK virus reactivation. In the kidney transplant population, BK virus, a polyomavirus, fi rst emerged as a clinical concern only in the mid1990s, after the introduction of more potent immunosuppressive medications. A signifi cant correlation was observed between the emergence of the infection and of the immunosuppressive regimen containing lymphocytedepleting agents for induction therapy followed by maintenance with calcineurin inhibitors (CNIs) and antiproliferative agents (mycophenolate mofetil, or MMF). At the current time, though, it seems more likely that the risk of BK virus reactivation relates to the total burden of immunosuppression, not to any one drug. Although the majority of reactivation occurs in the fi rst year posttransplant, BK virus nephropathy is a well-known cause of late allograft dysfunction. Risk factors for the condition include male gender, history of acute rejection, prolonged cold ischemia time, and degree of HLA mismatch. A robust association has been demonstrated between BK virus nephropathy and recipient seronegativity at the time of transplantation, similar to the epidemiology of other opportunistic viruses— e.g., herpes viruses, Epstein-Barr virus, and cytomegalovirus. Despite this known risk, testing for BK virus serostatus is not routinely performed, probably because seropositive renal transplant recipients can also develop BK virus nephropathy. Thus, although the precise etiopathogenesis remains unclear, BK virus nephropathy likely arises from complementary determinants in the host, the allograft, and the virus, in the setting of immunosuppression. When BK virus nephropathy does occur, reported rates of graft loss have ranged from 10% to 80%.