American Journal of Transplantation 2006; 6: 20002005

Blackwell Munksgaard
C
2006 The Authors
Journal compilation
C
2006 The American Society of
Transplantation and the American Society of Transplant Surgeons
doi: 10.1111/j.1600-6143.2006.01403.x Minireview
BK Virus Infection in Transplant Recipients:
An Overview and Update
P. Randhawa
a,
and D. C. Brennan
b
a
Department of Pathology, Division of Transplantation
Pathology, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania, USA
b
Department of Medicine, Division of Nephrology,
Washington University, Saint Louis, Missouri, USA

Corresponding author: Parmjeet Randhawa,

randhawapa@msx.UPMC.edu
BK virus infection after kidney transplantation has
been a subject of great interest in the past decade.
This article traces the discovery of BK virus and the
subsequent development of our knowledge about this
emerging pathogen. The pathobiology of the virus is
summarized with particular reference to epidemiol-
ogy, interactions with host cell receptors, cell entry, cy-
toplasmic trafcking and targeting of the viral genome
to the nucleus. This is followed by a discussion of clin-
ical features, laboratory monitoring and therapeutic
strategies. Finally, we present potential cellular mech-
anisms that explain the basis of virus-mediated dam-
age to the human kidney.
Key words: BK virus, epidemiology, JC virus, kid-
ney, pathobiology, pathogenesis, polyomavirus, renal,
SV40 virus, transplantation
Received 30 March 2006, revised 16 April 2006 and
accepted for publication 18 April 2006
Virology
Polyomavirus BK virus (BKV) is a double-stranded DNA
virus with a 5-kb genome. It has been classied in the Poly-
omaviridae family, which includes JC virus (JCV), a well
known cause of progressive multifocal leukoencephalopa-
thy, and the simian virus SV40 (1). The BKV genome com-
prises the non-coding control region (NCCR), the early-
coding region coding for the small and large T antigens,
and the late-coding region coding for the viral capsid pro-
teins (VP1, VP2 and VP3) and agnoprotein. The NCCR con-
tains (a) the origin of replication (ori) and (b) the regulatory
regions containing enhancer elements that can alter viral
transcription. T antigen binds to tumor suppressor proteins
Rb and p53 and initiates the cell cycle in host cells. VP1,
VP2 and VP3 are structural proteins that make up the viral
capsid. The VP1 gene displays considerable genetic hetero-
geneity, and this genetic variation has led to recognition of
viral genotypes I, II, III and IV. Agnoprotein plays a role in
several cellular processes, including cell cycle progression,
DNA repair, viral capsid assembly and virion release from
cell.
Historical Aspects
BKV was rst isolated in 1970 from a Sudanese kidney
transplantation recipient with a ureteric stricture. Epidemi-
ological studies showed that up to 90% of some human
populations become exposed to BKV by adulthood (1). Af-
ter kidney transplantation, 1060% of patients were noted
to excrete virus in the urine. However, viruria was typically
asymptomatic or associated with only transient graft dys-
function, though occasionally, virus-induced tissue damage
was noted at allograft nephrectomy or at autopsy. A new
era in the study of BKV began when BKV nephropathy
(BKVN) was diagnosed by a needle biopsy in a renal trans-
plant recipient suspected of having acute rejection. This
case was diagnosed in 1993 at Pittsburgh and published
in 1996. In the following years, additional cases were re-
ported from kidney transplant centers worldwide (25). It
is commonly believed that this epidemic of BKVN in the
1990s is the result of potent immunosuppressive drugs
such as tacrolimus, mycophenolate mofetil and sirolimus.
Mode of Transmission
Given that polyomavirus is latent in the kidney, it is not
surprising that the donor kidney itself appears to be an im-
portant source of infection in transplant recipients. Donor
seropositivity has been implicated in development of BK
viruria, viremia or BKVN in pediatric and adult transplant
recipients (69). The mode of viral transmission in the gen-
eral population is incompletely understood, but multiple
routes of infection are likely involved (1). Thus, BKV DNA
has been amplied from 040% of urine samples, and
1%of nasopharyngeal aspirates obtained frominfants with
respiratory infections. The possibility of feco-oral transmis-
sion has been recently raised by the demonstration of vi-
ral DNA in urban sewage. Blood, semen, genital tissues
and normal skin biopsies have also been shown to contain
BKV. Transplacental transmission of polyomaviruses from
mother to fetus has been recorded.
2000
BK Virus
Cell Entry and Intracellular Trafcking
BKV interactions with host cellular receptors have been
the subject of only limited investigations. The primary re-
ceptor binding determinant on BKV is the VP1 protein. The
host cell receptor for BKV appears to be an N-linked gly-
coprotein, in which GT1b and GD1b have been identied
as component gangliosides (10). Both these gangliosides
have an a-(2-8) linked di-sialic acid-motif as a common fea-
ture. An a-(2-3) sialic acid linkage has also been shown
to be important (10,11). Despite considerable homology at
the genetic level, BKV differs from other polyomaviruses
with regard to the chemical nature of its receptor. Thus, the
JCV receptor is an N-linked glycoprotein containing termi-
nal a-(2-3)- and a-(2-6)-linked sialic acids. The mouse poly-
omavirus binds to receptors containing a-(2-3)-linked sialic
acid N-glycoproteins as well as a4b1 integrins. SV40 VP1
interacts with major histocompatibility class I proteins and
O-linked glycan molecules.
The mode of BKV entry into the cell and routes of intra-
cellular trafcking are currently being claried. Electron mi-
croscopic observations on human biopsy material show
that BKV entry into host cells is similar to SV40, and medi-
ated by non-clathrin coated vesicles resembling caveolae.
In contrast, JCV enters the cell by clathrin-dependent endo-
cytosis. The mechanisms of endocytosis and intra-cellular
trafcking utilized by BKV have not been investigated in de-
tail. However, it has been established that the route from
cell membrane to the nucleus includes the endoplasmic
reticulumand microtubules (12,13). There may also be par-
ticipation of the Golgi apparatus, and other cytoskeletal el-
ements such as actin, and microlaments, as has been
shown for other members of the polyomavirus family. The
mechanism by which polyomavirus traverses the nuclear
envelope to enter the nucleus is only partially understood.
VP2 and VP3 contain a nuclear transport signal that may
facilitate nuclear targeting of the viral mini-chromosome.
Nucleoporin, a protein associated with the nuclear pore
complex, has also been implicated. The uncoating process
of polyomaviruses has been stated to occur after the viri-
ons have entered the cell nuclei, but it has been shown for
SV40 virus that some disassembly can occur in the endo-
plasmic reticulum.
Risk Factors for Infection
Conicting information has been reported on risk factors
for BK infection in transplant recipients (9,1416). Risk fac-
tors may be donor, recipient, transplant or virus related. Re-
ported donor-related factors include deceased-donor ver-
sus living-donor transplant, the presence of active BKV or
cytomegalovirus (CMV) infection, donor seropositivity and
the absence of HLA-C7. Reported recipient-related risk fac-
tors include older age, male gender, Caucasian race, di-
abetes mellitus, CMV infection, prior renal tubule injury,
recipient seronegativity and the absence of HLA-C7. Risk
factors associated with transplantation include procure-
ment injury, cold-ischemia time, delayed graft func-
tion, immunosuppression, especially with maintenance
tacrolimus, mycophenolate mofetil or sirolimus, or treat-
ment of acute rejection with lymphocyte depleting agents
or steroids, drug-toxicity, and increased number of HLA
mismatches. Viral-related factors include variants in VP1
and sequence alterations in the NCCR. Most of these risk
factors are unavoidable, unable to be modied or their risk
contribution has not been consistently shown from study
to study, perhaps because the type and intensity of im-
munosuppression may override any individual or combi-
nation of risk factors. Thus, the type and degree of im-
munosuppression is the most modiable factor. A random-
ized prospective trial of 200 kidney transplant recipients
showed that the incidence of BK viruria or viremia was not
increased with thymoglobulin induction as compared to no
induction, use of tacrolimus as compared to cyclosporine
or the use of mycophenolate mofetil as compared to aza-
thioprine (15). However, using detection of BK viruria or
viremia as a surrogate for the intensity of immunosuppres-
sion, the combination of tacrolimus and mycophenolate or
cyclosporine and azathioprine were the most potent, and
the combination of cyclosporine and mycophenolate the
least potent for the development of BK viruria or viremia.
An interventional strategy with discontinuation of the anti-
metabolite upon detection of viremia was used and no
BKVNwas observed. Thus, it appears that it may not be the
type but rather the intensity of immunosuppression that is
the greatest risk factor for BK infection and thus BKVN.
Systematic clinical observations of human subjects un-
dergoing polyomavirus seroconversion have not been re-
ported, and the role of BKV antibodies remains unclear.
An increasing anti-BK antibody titer has been seen to de-
velop with a decrease of immunosuppression and treat-
ment of BKVN (17). However, high-titer anti-BK antibody in
the donor has been associated with an increased likelihood
of development of BK viruria and viremia in the recipient
(18).
Clinical Features
The most frequent symptom associated with BKV infec-
tion is an upper respiratory infection. Sporadic reports of
acute cystitis, with or without hematuria, are also reported.
After primary infection has resolved, the virus enters a la-
tent phase. It appears that viral latency can be maintained
in a number of different sites, particularly the urogenital
tract (kidneys, urinary bladder, prostate, cervix and vulva,
as well as testes, prostate and seminiferous tubules, as
detected in semen) and hematolymphoid tissues (periph-
eral blood mononuclear cells, tonsils). Reactivation of latent
virus has been reported in old age, pregnancy and diabetes
mellitus, and immunosuppression associated with congen-
ital immunodeciency, organ transplantation or HIV infec-
tion. The most striking feature of BK infection in kidney
American Journal of Transplantation 2006; 6: 20002005 2001
Randhawa and Brennan
transplant recipients is the lack of fever, malaise, myalgias,
leukopenia, anemia, thrombocytopenia or other symptoms
or signs typical of viral infection, despite viral loads exceed-
ing a billion copies/mL in the urine or 100 000 copies/mL
in the blood (15,16). BKVN presents with renal dysfunction
without other clinical signs or symptoms.
Laboratory Diagnosis and Monitoring
Laboratory monitoring strategies for BKV are still evolving.
Quantitative nucleic acid-based viral load assay of urine or
blood are becoming widely used for BKV screening (15,19
22). Detectable virus in the blood is more predictive of
BKVNthan viruria alone. Some medical centers prefer urine
cytology as the primary screening technique (23,24). While
urinary decoy cells have excellent sensitivity for the de-
tection of overt BKVN, polymerase chain reaction (PCR) is
four times more sensitive than urine cytology for monitor-
ing asymptomatic viruria (25). Additionally, PCR provides a
more objective estimate of true viral load, and can distin-
guish BK viruria from JC viruria. JCV excretion in the urine
is usually insignicant, although very rare cases of JCV-
associated interstitial nephritis are on record. Decoy cells
are not stable, whereas DNA is, and PCR may be used
for monitoring of patients at a distance from the transplant
center. The relative costs of PCR versus cytology are a
center-dependent variable. Laboratory screening for BKV
should certainly be done for any unexplained rise in serum
creatinine. In addition, it is very desirable to monitor pa-
tients periodically, and one potential monitoring strategy
is shown in Figure 1. The cost-effectiveness of screening
has been formally evaluated in only one study to date (26).
In this investigation, it was determined that routine BKV
BLOOD BK-PCR MONTHS 1, 2, 3, 6 and 12, and UPON RENAL DYSFUNCTION
BLOOD BK-PCR
+
Increased serum creatinine Normal serum creatinine
Biopsy Decrease Immunosuppression and
Monitor q 2 weeks until clear
Rejection + BKVN BKVN alone No BKVN Increased creatinine Normal creatinine
1) Rx rejection with IVIG
& consider 26
2) Decrease immunosuppression Repeat biopsy Follow-up
3) Quinolone or cidofovir?
4) Leflunomide to replace the antimetabolite?
5) Monitor creatinine
6) Monitor BK q 2 weeks until clear
Figure 1: BK monitoring algorithm.
screening becomes cost-effective only if the incidence of
BKVN in a transplant program exceeds 2.1%. The cost of
screening was found to be substantially offset by the sav-
ings related to reductions in immunosuppression follow-
ing diagnosis of BKVN. No anti-viral agents were adminis-
tered. The assumptions made in this study regarding the
incidence of BKVN, cost of testing, management strategy
and risk of graft loss may not be applicable to all medical
centers in the United States.
Denitive diagnosis of BKVNrequires a biopsy and demon-
stration of BKV inclusions in tubular epithelial or Bowmans
capsular epithelial cells. Viral infection is accompanied by
varying degrees of inammatory cell inltrates, tubular at-
rophy and brosis. The cytopathic effect seen by light
microscopy is typical, but not pathognomonic for BKVN.
Conrmatory immunohistochemistry or in situ hybridiza-
tion studies are usually performed using antibodies against
specic for BKV proteins or probes complementary to vi-
ral DNA (Figure 2). Electron microscopy can be used to
demonstrate unenveloped, viral particles, approximately
40 nm in diameter. Since BKVN can be focal in distribution,
ideally two biopsy cores should be examined. The avail-
ability of medullary parenchyma increases the diagnostic
sensitivity. Negative biopsy results cannot rule out BKVN
with certainty, and a diagnosis of presumptive BKVN can
be made if there is renal allograft dysfunction associated
with BK viremia.
Biopsy ndings have been shown to have prognostic signif-
icance and three histological patterns of BKVN have been
proposed: (a) BKVN A: mild viral cytopathic changes, with
little or no inammatory inltrates or brosis, (b) BKVN B:
mild to moderate viral cytopathic changes with signicant
2002 American Journal of Transplantation 2006; 6: 20002005
BK Virus
Figure 2: BK virus replication in
the nucleus of a renal tubular ep-
ithelial cell, as demonstrated by
a uorescein-labeled antibody di-
rected against VP1, a viral capsid
proteinthat is synthesizedlate inthe
lytic life cycle.
inammatory inltrates, but limited brosis ( ci1+) and
(c) BKVN C: prominent tubular atrophy and interstitial bro-
sis, with usually sparse cytopathic changes, and variable
inammatory inltrates. BKVN A carries the best progno-
sis, while BKVN C is associated with the worst long-term
outcome (27).
Inammatory cell inltrates and tubulitis in biopsies with
BKVN may represent an immune response to the infec-
tion or concurrent allograft rejection. A denitive diagnosis
of rejection concurrent with viral nephropathy should only
be made if there is endarteritis, brinoid arterial necrosis,
glomerulitis or accumulation of the complement degrada-
tion product C4d along peritubular capillaries.
Pathogenesis
The pathogenesis of tissue damage in polyomavirus in-
fected tissues is a subject of considerable interest. Tran-
sition from latent to lytic infection in the human kid-
ney is likely initiated by ischemic, calcineurin inhibitor,
or rejection-associated injury. This would explain, in part
why most cases of BKVN occur in the allograft kidney,
although disease in the native organ has been recorded.
Using DNA microarray analysis of allograft kidney biop-
sies, it has been shown that BKVN is associated with
up-regulation of several major groups of mRNAs, includ-
ing CD8, Interferon-c , CXCR3 and perforin. It is notable
that these molecules are also up-regulated in acute cellu-
lar rejection, and this illustrates why the differential diagno-
sis between viral nephropathy and acute cellular rejection
is problematic (28). Additionally, there is up-regulation of
molecules associated with graft brosis, including matrix
collagens, TGF-b, MMP2, MMP9 and markers of epithelial-
mesenchymal transformation. The latter nding attests to
the role of viral infection in promoting chronic allograft
nephropathy.
Treatment
The treatment of BKVN is unsatisfactory, since no uni-
formly effective anti-viral drugs are currently available. Pre-
vention of BKVN may be a better strategy than treatment
of established disease. One large study of patients with
prospective monitoring of urine and blood, and preemp-
tive withdrawal of the anti-metabolite upon development
of viremia, showed that this strategy resulted in clearance
of viremia and viruria, and appeared to prevent progres-
sion to BKVN without increasing the risk of acute rejec-
tion (15). Another smaller prospective study showed that
viremia and viruria could resolve or decrease over time
with standard reductions in immunosuppression, without
preemptive withdrawal of any component of the immuno-
suppressive regimen (16). Reducing the intensity of main-
tenance, immunosuppression currently represents the
primary treatment of well established BK nephropathy.
However, in patients with progressive graft dysfunction not
responding to this maneuver, anti-viral treatment should
be considered. Protocols and success rates are hetero-
geneous, with graft loss ranging from <10% to >80%
(14). Anti-viral agents used with anecdotal success in-
clude cidofovir, leunomide, quinolone antibiotics and intra-
venous immunoglobulin (14,2932). The efcacy of these
strategies is unclear, because reduction of immunosup-
pression has been used along with all of the strategies.
Additionally, an in vitro study has shown that the 50%
American Journal of Transplantation 2006; 6: 20002005 2003
Randhawa and Brennan
effective concentration (EC50) for either leunomide (39.7
lg/mL) or cidofovir (36.3 lg/mL) is higher than what may
be achieved clinically with conventional dosing (33). Blood
leunomide levels above 40 lg/mL in the context of other
reductions of immunosuppression have been associated
with viral clearance or decrease in BK-viral load, but the
pharmacokinetics of leunomide are unpredictable, and
even patients on 60 mg/day may fail to achieve 40 lg/mL
(30,34). For cidofovir, the EC50 is much higher than peak
plasma concentrations that are typically achieved with the
low-dose (0.251.0 mg/kg) treatment regimens described
in most publications related to BKVN (33). Esterication
of cidofovir with hexadecyloxypropyl, octadecyloxyethyl
or oleyloxyethyl groups results in up to 3-log lowering of
EC
50
and markedly increased selectivity index in vitro. Oral
bioavailability and reduced nephrotoxicity are additional po-
tential advantages of these derivatives over unmodied
cidofovir (35). A cautiously conducted controlled clinical
trial of these compounds in the management of BKVN
appears to be warranted. Re-transplantation is safe and
usually not complicated by recurrent BKV infection in the
recipient. If allograft nephrectomy is performed, preemp-
tive re-transplantation may be performed even during the
phase of active viremia (36).
In conclusion, there is increasing recognition of BKV infec-
tions after kidney transplantation. Improved techniques of
clinical monitoring and preemptive adjustment of immuno-
suppression have led to a reduction in the incidence of
overt viral nephropathy. However, in patients who do de-
velop BKV-induced allograft injury, we do not have reliable
anti-viral drugs available at this time. The impact of long-
term low-grade viruria or viremia on the development of
chronic allograft nephropathy requires further study.
Acknowledgments
Dr Brennan acknowledges receiving research support from Novartis Phar-
maceuticals, Astellas Pharmaceuticals, Roche Pharmaceuticals, Wyeth
Pharmaceuticals, Pzer Laboratories and Genzyme. This work was sup-
ported by NIH grants R01 AI 51227, AI 63360 (P.R.) and K24 DK02886
(D.C.B.).
References
1. Randhawa PS, Vats A, Shapiro R et al. BK virus: Discovery, epi-
demiology, and biology. Graft 2002; 2 (Suppl 5): S19S27.
2. Hariharan S. BK virus nephritis after renal transplantation. Kidney
Int 2006; 69: 655662.
3. Ramos E, Drachenberg CB, Papadimitriou JC et al. Clinical course
of polyoma virus nephropathy in 67 renal transplant patients. J
Am Soc Nephrol 2002; 13: 21452151.
4. Randhawa PS, Finkelstein S, Scantlebury V et al. Human poly-
oma virus-associated interstitial nephritis in the allograft kidney.
Transplantation 1999; 67: 103109.
5. Nickeleit V, Hirsch HH, Zeiler M et al. BK-virus nephropathy in
renal transplants-tubular necrosis, MHC-class II expression and
rejection in a puzzling game. Nephrol Dial Transplant 2000; 15:
324332.
6. Smith JM, McDonald RA, Finn LS et al. Polyomavirus nephropathy
in pediatric kidney transplant recipients. Am J Transplant 2004; 4:
21092117.
7. Andrews CA, Shah KV, Daniel RWet al. Aserological investigation
of BK virus and JC virus infections in recipients of renal allografts.
J Infect Dis 1988; 158: 176181.
8. Ginevri F, De Santis R, Comoli P et al. Polyomavirus BK infection
in pediatric kidney-allograft recipients: A single-center analysis of
incidence, risk factors, and novel therapeutic approaches. Trans-
plantation 2003; 75: 12661270.
9. Bohl DL, Storch G, Ryschkewitsch C et al. Donor origin of BK
virus in renal transplantation and role of HLA C7 in susceptibility
to sustained BK viremia. Am J Transplant 2005; 5: 22132221.
10. Gilbert J, Dahl J, Riney C et al. Ganglioside GD1a restores in-
fectibility to mouse cells lacking functional receptors for poly-
omavirus. J Virol 2005; 79: 615618.
11. Dugan AS, Eash S, Atwood WJ. An N-linked glycoprotein with
alpha-(2, 3)-linked sialic acid is a receptor for BK virus. J Virol 2005;
79: 1444214445.
12. Low JA, Magnuson B, Tsai B et al. Identication of gangliosides
GD1b and GT1b as receptors for BK virus. J Virol 2006; 80: 1361
1366.
13. Eash S, Atwood WJ. Involvement of cytoskeletal components in
BK virus infectious entry. J Virol 2005; 79: 1173411741.
14. Hirsch HH, Brennan DC, Drachenberg CB et al. Polyomavirus-
associated nephropathy in renal transplantation: Interdisciplinary
analyses and recommendations. Transplantation 2005; 79: 1277
1286.
15. Brennan DC, Agha I, Bohl DL et al. Incidence of BK with tacrolimus
versus cyclosporine and impact of preemptive immunosuppres-
sion reduction. Am J Transplant 2005; 5: 582594.
16. Bressollette-Bodin C, Coste-Burel M, Hourmant M et al. A
prospective longitudinal study of BK virus infection in 104 renal
tranplant recipients. Am J Transplant 2005; 5: 19261933.
17. Hariharan S, Cohen EP, Vasudev B et al. BK virus-specic antibod-
ies and BKV DNA in renal transplant recipients with BKV nephritis.
Am J Transplant 2005; 5: 27192724.
18. Bohl DL, Ryschkewitsch C, Major EO et al. BK virus antibody
titers markedly increase with viremia. Am J Transplant 2005; 5:
273273.
19. Randhawa P, Ho A, Shapiro R et al. Correlates of quantitative
measurement of BK polyomavirus (BKV) DNA with clinical course
of BKV infection in renal transplant patients. J Clin Microbiol 2004;
42: 11761180.
20. Limaye AP, Jerome KR, Kuhr CSet al. Quantitation of BKvirus load
in serum for the diagnosis of BK virus-associated nephropathy in
renal transplant recipients. J Infect Dis 2001; 183: 16691672.
21. Biel SS, Held TK, Landt O et al. Rapid quantication and differen-
tiation of human polyomavirus DNA in undiluted urine from pa-
tients after bone marrow transplantation. J Clin Microbiol 2000;
38: 36893695.
22. Leung AY, Chan M, Tang SC et al. Real-time quantitative analy-
sis of polyoma BK viremia and viruria in renal allograft recipients.
J Virol Methods 2002; 103: 5156.
23. Drachenberg CB, Hirsch HH, Ramos E et al. Polyomavirus disease
in renal transplantationReview of pathological ndings and di-
agnostic methods. Hum Pathol 2005; 36: 12451255.
24. Singh HK, Bubendorf L, Mihatsch MJ et al. Urine cytology nd-
ings of polyomavirus infections. In: Ahsan N, ed. Polyomavirus
and Human Diseases. Jacksonville: Springer Science + Business
Media, Landes Bioscience/Eurekah.com, 2006: 201212.
2004 American Journal of Transplantation 2006; 6: 20002005
BK Virus
25. Randhawa P, Vats A, Shapiro R. Monitoring for polyomavirus BK
and JC in urine: Comparison of quantitative polymerase chain re-
action with urine cytology. Transplantation 2005; 79: 984986.
26. Kiberd BA. Screening to prevent polyoma virus nephropathy: A
medical decision analysis. Am J Transplant 2005; 5: 24102416.
27. Drachenberg CB, Papadimitriou JC, Hirsch HH et al. Histological
patterns of polyomavirus nephropathy: Correlation with graft out-
come and viral load. Am J Transplant 2004; 4: 20822092.
28. Mannon RB, Hoffmann SC, Kampen RL et al. Molecular evaluation
of BK polyomavirus nephropathy. Am J Transplant 2005; 5: 2883
2893.
29. Leung AYH, Chan MTL, Yuen KY et al. Ciprooxacin decreased
polyoma BK virus load in patients who underwent allogeneic
hematopoietic stemcell transplantation. Transplantation 2005; 40:
528537.
30. Williams JW, Javaid B, Kadambi PV et al. Leunomide for poly-
omavirus type BK nephropathy. N Engl J Med 2005; 352: 1157
1158.
31. Sener A, House AA, Jevnikar AMet al. Intravenous immunoglobu-
lin as a treatment for BK virus associated nephropathy: One-year
follow-up of renal allograft recipients. Transplantation 2006; 81:
117120.
32. Randhawa PS. Anti-BK virus activity of ciprooxacin and related
antibiotics. Clin Infect Dis 2005; 41: 13661367.
33. Farasati NA, Shapiro R, Vats A et al. Effect of leunomide and
cidofovir on replication of BK-virus in an in vitro culture system.
Transplantation 2005; 79: 116118.
34. Josephson MA, Gillen D, Javaid B et al. Treatment of renal allo-
graft polyoma BK virus infection with leunomide. Transplantation
2006; 81: 704710.
35. Randhawa P, Farasati N, Shapiro R et al. Ether lipid ester deriva-
tives of cidofovir inhibit polyomavirus BK replication in vitro. An-
timicrob Agents Chemother 2006; 50: 15641566.
36. Womer KL, Meier-Kriesche HU, Bucci CM et al. Pre-emptive re-
transplantation for BK virus nephropathy: Successful outcome de-
spite active viremia. Am J Transplant 2006; 6: 209213.
American Journal of Transplantation 2006; 6: 20002005 2005