0508_NewsPath-Renal_Allograft_and_the_BK_Virus.doc Page 1 of 2

NewsPath® Editor: Megan J. DiFurio, MD, FCAP This newsletter is produced in cooperation with the College of American Pathologists’ Public Affairs Committee and may be reproduced in whole or in part as a service to the medical community. Copyright © 2005

Renal Allograft and the BK Virus Oyedele Adeyi, MB, BS College of American Pathologists’ Surgical Pathology Committee

One of the greatest challenges to achieving an optimum rejection-free experience for renal allograft recipients is the need to balance adequate immunosuppression with prevention of infection. Opportunistic agents constitute a major group of infectious agents that have confounded transplant physicians and immunologists because they are difficult to both diagnose and treat. One agent in particular, the BK virus (BKV)—a member of the polyoma virus group, which also includes the JC virus and the SV40 agents—presents a significant problem to transplant specialists.

The BKV is usually acquired early in life, often asymptomatic, and capable of reactivation from latency in an immunosuppressed host. Among renal transplant patients, positive urine and/or serum BKV DNA can be demonstrated by cytologic or molecular means, without evidence of graft infection or BKV-associated nephropathy (BKVAN). However, by an average of 40 weeks post-transplantation, up to 5% of renal allograft recipients can be expected to develop BKVAN, with progression to irreversible failure of the allograft in up to 45% of these cases.1 In addition, BKV infection has been implicated as the cause of ureteric strictures in renal transplant recipients.2

It is therefore essential that the diagnosis of BKVAN be made and treatment instituted as soon as possible to prevent graft loss. As opposed to BKVAN, allograft rejection, the most important differential diagnosis, would require increased immunosuppression instead of antiviral therapy. The correct diagnosis and treatment in a timely manner are vitally important for graft survival.

The diagnosis of BKVAN requires a combination of clinical and laboratory findings, but the gold standard remains the identification of characteristic viral inclusions, sometimes with the help of immunohistochemistry, in biopsy materials obtained from the graft (Figure 1).

It is important for the clinician to know when a biopsy is required and to perform it at a center with facilities for processing these specimens, preferably as “stat” requests. Interpreting the biopsy also requires appropriate expertise by the pathologist, who should be aware of the focal nature of the characteristic viral inclusions and actively search for them.

0508_NewsPath-Renal_Allograft_and_the_BK_Virus.doc Page 2 of 2

NewsPath® Editor: Megan J. DiFurio, MD, FCAP This newsletter is produced in cooperation with the College of American Pathologists’ Public Affairs Committee and may be reproduced in whole or in part as a service to the medical community. Copyright © 2005

Figure 1: Typical inclusion of BK virus in renal epithelial cells:

nuclear enlargement with “smudgy” appearance (original magnification 100×).

So far attempts at identifying surrogate markers of BKVAN have had limited success and evaluation of biopsy material will probably remain the main diagnostic test for some time. The use of molecular methods on biopsy materials appears to be showing some promise.

A recent abstract presented at the 2005 annual United States & Canadian Academy of Pathology (USCAP) conference described the use of laser capture microdissection with real-time PCR techniques to detect the presence of this virus in renal allograft biopsy materials.3 However, the morphologic demonstration of viral inclusions remains the gold standard, and renal transplant clinicians continue to rely on pathologists to provide this all-important information for optimum patient care and prolongation of graft survival.

References:

1. Hirsch HH. Polyomavirus BK nephropathy: a (re-)emerging complication in renal transplantation. Am J Transplant. 2002;2(1):25-30

2. Coleman DV, Mackenzie EF, Gardner SD, et al. Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients. J Clin Pathol. 1978;31:338-47.

3. Adeyi OA, Belloni DR, Dufresne SD, et al. Detection of BK virus in laser capture microdissected kidney biopsies using real-time PCR. Human Pathol. 2005;18(S):264A