Posted August 1, 2005
Oyedele Adeyi, MB, BS
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
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.
Figure 1: Typical inclusion of BK virus in
renal epithelial cells: nuclear
enlargement with “smudgy”
appearance (original magnification 100x).
(Download this image in a higher-resolution. 824 KB)
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.
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.
- Hirsch HH. Polyomavirus BK nephropathy: a (re-)emerging complication in renal transplantation. Am J Transplant. 2002;2(1):25-30
- 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.
- 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
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NewsPath® Editor: Megan
J. DiFurio, MD, FCAP
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