BK Polyoma Virus:
A Mini Tutorial
Joel C Reynolds, MD
Walter Reed Army Medical Center
Nephrology Service
What We Know:
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BKV seroprevalence is almost ubiquitous with
over 90% of all people seropositive by age 10.1
BKV nephropathy is a significant cause of renal
allograft loss.2
Urine shedding of BKV is more prevalent than
viremia.1,2
Primary infection with seroconversion has been
documented.1
To date all studies have shown 100% urine PCR
positivity when viremia is present by PCR.1,2
What We Know:
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BKV nephropathy can resemble acute
rejection on biopsy, usually unresponsive
to steroids when treated as rejection.3
Allograft biopsy is currently considered
the “gold standard” for diagnosis, but has
questionable sensitivity.3
BKV infected renal tubular epithelial
(decoy) cells appear to deteriorate quickly
(within minutes), which may limit urine
microscopy as a screening tool.4
What We Know:
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Urine BKV DNA load is usually at least
105x higher than serum viral DNA load
and may be present without viremia.5
No studies to date have identified clear
risk factors which would help predict
those at risk for BKV nephropathy, to
include tacrolimus, mycophenolate, or
steroids.2
What We Suspect:
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Overall immunosuppression levels are too high.
Prevalence is much higher than previously
suspected.
Antiviral drugs (cidofovir) may be effective
treatment.6
Failure to detect BKV early leads to irreversible
nephropathy.4
Allograft biopsy sensitivity for BKV is suspect
due to the spotty nature of early infection and
apparent predeliction of the virus for medullary
renal tissue.3
What We Don’t Know:
• Is there a reservoir for BKV other than urinary
tract?
• What are the risk factors for developing BKVN?
• Risk factors for reactivation of harbored BKV?
• Does serology of donor/recipient change risk?
• What level of serum BKV DNA denotes those at
increased risk of progression to BKVN?
• How does cidofovir (known to inhibit viral DNA
polymerase) inhibit BKV replication (which has
no DNA polymerase)?
What We Don’t Know:
• What is the most cost effective/sensitive test
to help predict those at increased risk for
developing BKVN?
– Serum PCR, very sensitive (4 copies/ml),
expensive (~$200), significance of levels?
– Urine PCR, very sensitive, expensive, not
specific, signficance of levels?
– Urine decoy cell microscopy, inexpensive,
operator/time dependent, significance of
positive finding?
What Is Needed?
• Large, prospective trials including transplant
recipients not on calcineurin inhibitors, and on
steroid free protocols, to adequately assess for risk
factors which would predispose to infection by
BKV.
• Likely would require multi-center cooperation to
achieve power to detect factors with significance
(similar to the studies of CMV status of
donor/recipient performed in the ‘70s).
References:
1.
Hirsch HH, et.al. Prospective study of polyomavirus type BK replication
and nephropathy in renal-transplant recipients. N Engl J Med. 2002 Aug
15;347(7):488-96.
2.
Ramos E, et.al. Clinical course of polyoma virus nephropathy in 67 renal
transplant patients. J Am Soc Nephrol. 2002 Aug;13(8):2145-51.
3.
Drachenberg RC, et.al. Morphological spectrum of polyoma virus disease
in renal allografts: diagnostic accuracy of urine cytology. Am J Transplant
2001 Nov;1(4):373-81.
4.
Personal observations in our clinic (Walter Reed AMC).
5.
Brennan DC, unpublished data, Washington Univ School of Medicine, St.
Louis, MO.
6.
Vats A, et.al. Quantitative viral load monitoring and cidofovir therapy for
the management of BK virus-associated nephropathy in children and
adults.Transplantation. 2003 Jan 15;75(1):105-12.
7.
Nickeleit V, et.al. BK virus infection after kidney transplantation. Graft.
2002 Dec; S18 (5): S46-57.
A Pictorial Tutorial
Unstained Freshly-Voided Urine with
Decoy Cells:
(Renal Tubular Epithelial cells with BKVAssociated Intranuclear Inclusions)
Digital photographs courtesy of Mr.
David Oliver and Mrs. Luana Kiandoli,
Nephrology Laboratory, WRAMC
Type I: An amorphous ground-glass variant
“Ground-glass” appearance of nucleus
Reference 7
400x (Olympus BH2 microscope)
Type II: granular variant surrounded by a “halo”
Reference 7
400x (Olympus BH2 microscope)
Type III: a finely granular variant without halo
Reference 7
400x (Olympus BH2 microscope),
Enlarged 1.6x in processing image.
Type II/III hybrid:
Intranuclear
vesicles
Reference 7
400x (Olympus BH2 microscope),
Enlarged 2x in processing image.
Type IV: a vesicular variant with clumped, irregular
chromatin
Reference 7
400x (Olympus BH2 microscope),
Enlarged 2x in processing image.