LIVER TRANSPLANTATION 14:1787-1792, 2008

ORIGINAL ARTICLE

Decline in Native Kidney Function in Liver

Transplant Recipients Is Not Associated with BK
Virus Infection
Muna Salama,1 Neil Boudville,2,3 David Speers,4 Garry P. Jeffrey,1,3 and Paolo Ferrari3,5
1
Department of Gastroenterology/Hepatology, 2Department of Renal Medicine, and 3School of Medicine
and Pharmacology, University of Western Australia, Perth, Australia; 4PathWest, Laboratory Medicine, Sir
Charles Gairdner Hospital, Perth, Australia; and 5Department of Nephrology, Fremantle Hospital, Perth,
Australia

BK virus (BKV) infection is an established cause of allograft dysfunction in renal transplant recipients. The relationship between
BKV infection and chronic kidney disease (CKD) post– orthotopic liver transplantation (OLT) is not well understood. This study
aimed to determine the prevalence of BKV infection, its relationship to CKD and renal function loss over time in patients
receiving OLT. Prevalence of BK viruria and viremia were studied in 41 post-OLT patients after a mean 6.5 ⫾ 4.7 years
posttransplantation. Renal function was assessed using estimated glomerular filtration rate (eGFR) calculated from the yearly
serum creatinine levels using the Modification of Diet in Renal Disease (MDRD) formula. Polymerase chain reaction (PCR) was
performed for detection of BKV DNA in urine and plasma. BK viruria was present in 24.2% of patients, but none of these OLT
recipients had detectable BK viremia. Decoy cells in the urine were found in 9.7% patients, although none of these patients had
BK viruria. CKD, defined as eGFR ⬍60 mL/minute/1.73 m2, was found in 83% of OLT recipients. The yearly decline in eGFR
was ⫺6.9 ⫾ 17 and ⫺9.2 ⫾ 18 mL/minute/year in BK viruria–positive and BK viruria–negative patients, respectively (P ⫽ 0.39).
There was no relationship between the presence or absence of BK viruria and either current eGFR, yearly decline in eGFR,
number and type of immunosuppressive agents, or etiology of liver failure. In OLT recipients, BK viruria is not associated with
BK viremia or native kidney dysfunction. It appears that the most probable pathway for the development of BKV nephropathy
requires a second hit, such as kidney inflammation, kidney ischemia, or donor-recipient human leukocyte antigen mismatch.
Liver Transpl 14:1787-1792, 2008. © 2008 AASLD.

Received April 28, 2008; accepted July 24, 2008.

The BK virus (BKV) is a ubiquitous small DNA virus
that belongs to the family of human polyomaviruses.
BKV was first isolated from the urine of a renal trans-
plant recipient in 1971.1 Seroprevalence studies have
shown antibodies to BKV in 60%-80% of adults.2,3 Al-
though the seroprevalence of BKV in humans is high,
clinical disease among immunocompetent patients is
uncommon and BKV-associated diseases occur pre-
dominantly in the setting of immunosuppression. After
primary infection the virus remains latent in B-lympho-
cytes and in the kidney. Predictably the major diseases
caused by BKV are tubulointerstitial nephritis and ure-
teral stenosis in renal transplant recipients4 and hem-
orrhagic cystitis in bone marrow transplant recipients.5
In renal transplantation recipients, BKV has been
shown to be associated with graft nephropathy.4,6,7
BKV nephropathy affects 1%-10% of kidney transplan-
tation patients, with graft failure or loss in up to 80% of
cases.8
Chronic kidney disease (CKD) is very common after

Abbreviations: BKV, BK virus; CKD, chronic kidney disease; CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate;
GFR, glomerular filtration rate; LT, liver transplantation; MDRD, Modification of Diet in Renal Disease; OLT, orthotopic liver
transplant; PCR, polymerase chain reaction.
Supported in part by the Ruth Mortimer bequest.
Address reprint requests to Paolo Ferrari, M.D., School of Medicine and Pharmacology, University of Western Australia and Department of
Nephrology, Fremantle Hospital, Alma Street, Perth, WA 6160, Australia. Telephone: 0061 8 9431 3600; FAX: 0061 8 9431 3619;
E-mail: paolo.ferrari@health.wa.gov.au
DOI 10.1002/lt.21627
Published online in Wiley InterScience (www.interscience.wiley.com).

© 2008 American Association for the Study of Liver Diseases.

1788 SALAMA ET AL.
liver transplantation (LT) with rates of severe chronic
renal failure, defined as a glomerular filtration rate
(GFR) of ⬍30 mL/minute/1.73 m2, reported to be as
high as 18% at 60-month follow-up.9 The cause of renal
dysfunction after LT is often multifactorial, although
calcineurin inhibitor nephrotoxicity is considered to be
the main contributor to CKD in this population. Other
known risk factors for CKD in LT recipients include
pretransplantation renal disease, hepatitis C virus in-
fection, diabetes, increased age, male sex, and Asian
race.9 Histological examination of renal biopsies after
orthotopic LT (OLT) suggest that there may well be
other contributors that have not, as yet, been fully ap-
preciated.10
There is some evidence that BKV plays a role in renal
dysfunction in other solid organ transplants with doc-
umented cases of BKV nephropathy after heart,11,12
lung,13 and pancreas transplantation.14 In LT recipi-
ents the prevalence of BK viremia has been reported to
range between 0%-2.8% and the prevalence of viruria to
range between 8%-16%,15-17 with a 4.1% first-year in-
cidence in 121 LT recipients in 1 series18 However, the
clinical relevance of BKV infection in this population
has been poorly investigated. The aim of the present
study was to investigate the prevalence of BK viruria
and viremia in LT recipients and to compare current
renal function and the change in renal function over
time in BKV-negative versus BKV-positive patients.
PATIENTS AND METHODS
This cross-sectional point prevalence study of BKV dis-
ease in unselected LT recipients was approved by the
institute’s Human Research Ethics Committee. During
a period of 6 months, unselected LT recipients attend-
ing regular follow-up visits on a Thursday clinic were
enrolled in the study. Pediatric recipients, recipients of
dual liver and kidney transplants or those who had had
LT less than 12 months previously, and patients with
acute variations in renal function at the time of sam-
pling were excluded from the study. Standard immuno-
suppression used in this cohort consisted of initial tri-
ple therapy with cyclosporine, azathioprine, and
prednisolone, with steroid withdrawal at 3-6 months
posttransplantation. Tacrolimus and mycophenolate
mofetil were commenced when more potent immuno-
suppression was required and calcineurin inhibitors
were minimized in patients with signs of CKD. No anti-
body induction including basiliximab was used as a
standard therapy.
After obtaining informed consent, a representative
cohort of 41 patients, corresponding to 20% of OLT
recipients at our center, were recruited into the study.
Patients were interviewed and files were reviewed to
acquire information relevant to the study. Data col-
lected included age, sex, weight, race, cause of liver
failure, transplantation date, hepatitis B and C status,
current and previous immunosuppression regimen, the
average tacrolimus and cyclosporine levels in the pre-
ceding 12 months, yearly serum creatinine levels, and
proteinuria. Blood and urine samples were collected
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
from all patients for the detection of BK viremia or
viruria or characteristic cytopathologic cells. No routine
kidney biopsy was performed. Because BKV nephropa-
thy is unusual in the absence of BK viraemia,19 pa-
tients were offered the option of a renal biopsy only if
they tested positive for BK viremia and if their kidney
function showed a progressive decrease, or if it was
otherwise clinically indicated.
Analytical Methods
Polymerase chain reaction (PCR) of blood and urine
according to published methods19 and cytologic exam-
ination to detect urinary shedding of polyomaviruses as
described20 were performed in all samples. The thresh-
old level for a positive BK PCR test was ⬎150 copies/mL
for both urine and plasma. The urinary sediment was
also investigated for the presence of characteristic de-
coy cells with an enlarged nucleus with a single large
basophilic intranuclear inclusion. In accordance with
international recommendations21 the results of the
urine PCR were used to categorize patients into those
with and those without infection. The presence of decoy
cells was used to screen for possible BK-induced inter-
stitial nephritis. Serum creatinine was measured using
a kinetic colorimetric assay (Jaffe method) analyzed on
the Roche Hitachi 917 analyzer (Roche Diagnostic
GmbH, Mannheim, Germany). The coefficients of vari-
ation for this assay are 6.6% at 70.5 ␮mol/L, and 4.1%
at 485 ␮mol/L. GFR was estimated from serum creati-
nine utilizing the Modification of Diet in Renal Disease
(MDRD) formula.22 CKD was defined as an estimated
glomerular filtration rate (eGFR) ⬍60 mL/minute/1.73
m2, severe CKD was defined as an eGFR ⬍30 mL/
minute/1.73 m2.
Statistical Analysis
Statistical analysis was performed with the Systat for
Windows software package version 10 (SPSS, Inc., Chi-
cago, IL). Results are given as mean ⫾ standard devia-
tion for continuous variables and number and percent-
age for categorical variables. Differences between
subjects were tested by nonparametric Mann-Whitney
U test statistic for continuous data and Fisher exact
test for categorical data. The chi-square test was used
to detect differences between proportions. Multiple re-
gression analysis was used to assess possible factors
influencing renal function decline. The covariates in-
cluded in the multivariate models were gender, time
after transplantation, hepatitis status, current cal-
cineurin inhibitor (CNI) immunosuppression, mean
CNI blood level over the last 12 months, and BK viruria.
When current GFR was used as the dependent variable,
the yearly GFR change was also included in the covari-
ates and when the yearly GFR change was used as the
dependent variable, current GFR was included in the
covariates.
 BK VIRUS IN LIVER TRANSPLANTATION 1789

TABLE 1. Characteristics of 41 Orthotopic Liver Transplant Recipients by BK Viral Status at the Time
of BK Viral Screening

BK Viruria
Positive Negative P Value
N 10 31
Male gender 2 (20%) 17 (55%) 0.055
Age (years) 57 ⫾ 8 56 ⫾ 13 0.71
Years post-transplantation 4.4 ⫾ 3.6 6.7 ⫾ 3.9 0.11
Renal function
Serum creatinine (␮mol/L)
1 year post-transplantation 111 ⫾ 46 113 ⫾ 39 0.91
Current 112 ⫾ 12 126 ⫾ 42 0.09
⌬ change (␮mol/L/year) ⫹2.6 ⫾ 11 ⫹2.5 ⫾ 4.3 0.97
eGFR (mL/minute/1.73 m2)
1 year post-transplantation 63 ⫾ 19 58 ⫾ 20 0.44
Current 56 ⫾ 10 48 ⫾ 16 0.08
⌬ change (mL/minute/1.73 m2/year) ⫺3.4 ⫾ 6.1 ⫺1.6 ⫾ 2.6 0.21
Current immunosuppression
CNI 8 (80%) 28 (90%) 0.38
Cyclosporine 4 (40%) 21 (67%) 0.12
Tacrolimus 4 (40%) 6 (19%) 0.19
Azathioprine 5 (50%) 12 (39%) 0.86
Mycophenolate 4 (40%) 14 (45%) 0.44
Prednisolone 0 9 (29%) 0.053
BK virus (number of patients)
Decoy cells 0 4
Urine PCR 10 0
Blood PCR 0 0

NOTE: Values are number (%) or mean ⫾ standard deviation.

Abbreviations: CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate; PCR, polymerase chain reaction.

RESULTS
Of the 41 patients enrolled, 35 were Caucasians and 6
were Asians. The cause of liver failure requiring trans-
plantation was due to autoimmune hepatitis in 44%,
viral hepatitis in 29% (22% hepatitis C, 7% hepatitis B),
miscellaneous causes in 20%, and alcoholic cirrhosis in
7% of cases. The mean age of patients was 56 ⫾ 13
years, time since transplantation was 6.5 ⫾ 4.7 years,
and weight was 80 ⫾ 18 kg. The mean pretransplanta-
tion serum creatinine was 90 ⫾ 56 ␮mol/L and the
current value was 123 ⫾ 37 ␮mol/L.
In this cohort the prevalence of BK viruria was 24.3%
(10/41 patients). A comparison of patients with and
without BK viruria did not reveal any significant differ-
ence with regard to time after transplantation, renal
function, or use of immunosuppressive agents between
the 2 groups (Table 1). Positive urine cytology for decoy
cells was found in 9.7% (4/41) patients, although none
of these subjects tested positive for BK viruria by PCR.
None of the LT recipients had detectable BK viremia.
Moderate CKD (⬍60 mL/minute/1.73 m2) was diag-
nosed in 34 (83%) and severe CKD (⬍30 mL/minute/
1.73 m2) was found in 3 (7%) LT recipients. The yearly Figure 1. Relationship between current glomerular filtration
decline in eGFR was ⫺3.4 ⫾ 6.1 mL/minute/year in BK rate (GFR) and annual GFR change by BK viruria status. ●, BK
viruria–positive and ⫺1.6 ⫾ 2.6 mL/minute/year in BK viruria–negative; X, BK viruria–positive.
viruria–negative patients (P ⫽ 0.21). The relationship
between current GFR and annual GFR change by BK
viruria status is shown in Fig. 1.
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
1790 SALAMA ET AL.

TABLE 2. Characteristics of 41 Orthotopic Liver Transplantation Recipients by eGFR Below

or Above 60 mL/minute/1.73 m2

eGFR (mL/minute/1.73 m2)

⬍60 ⱖ60 P Value
N 34 7
Male gender 16 (47%) 3 (43%) 0.84
Age 57 ⫾ 8 49 ⫾ 12 0.092
Years post-transplantation 6.7 ⫾ 5.1 6.7 ⫾ 5.1 0.79
BK virus
Urine PCR 8 (24%) 2 (29%) 0.78
Renal function
1 year post-transplantation
Serum creatinine (␮mol/L) 118 ⫾ 42 88 ⫾ 21 0.014
Current
Serum creatinine (␮mol/L) 131 ⫾ 36 85 ⫾ 14 ⬍0.0001
eGFR (mL/minute/1.73 m2/year) 45 ⫾ 9 75 ⫾ 12 ⬍0.0001
Change in renal function
Serum creatinine (␮mol/L/year) ⫹2.7 ⫾ 6.8 ⫹2.2 ⫾ 4.6 0.85
eGFR (mL/minute/1.73 m2/year) ⫺2.0 ⫾ 3.7 ⫺2.4 ⫾ 4.4 0.81
Current immunosuppression
CNI 30 (88%) 6 (86%) 0.85
Cyclosporine 23 (67%) 2 (29%) 0.054
Tacrolimus 8 (24%) 2 (29%) 0.78
Azathioprine 15 (44%) 2 (29%) 0.45
Mycophenolate 13 (38%) 5 (71%) 0.11
Prednisolone 8 (24%) 1 (14%) 0.59

NOTE: Values are number (%) or mean ⫾ standard deviation.

Abbreviations: CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate; PCR, polymerase chain reaction.

Further analysis was done by comparing patients
with CKD (⬍60 mL/minute/1.73 m2) and those without
CKD (ⱖ60 mL/minute/1.73 m2) (Table 2). There was no
difference in the use of CNIs between patients with and
without CKD (Table 2), although current usage of CNIs
was associated with a more rapid decline in eGFR (2.5 ⫾
3.7 versus ⫺0.9 ⫾ 2.6 mL/minute/year, P ⬍ 0.05) after
the first year posttransplantation. In the multivariate
analysis, pretransplantation renal function, time after
transplantation, gender, hepatitis status, current use
of CNI, average CNI blood levels in the previous 12
months, or BK viruria did not influence the annual
change in eGFR. However, a low eGFR (⬍60 mL/
minute/1.73 m2) at 1 year after transplantation was
associated with improving renal function over time after
the first year posttransplantation (coefficient of vari-
ance ⫽ 0.068, P ⬍ 0.05). Because the MDRD formula is
not reliable in the high range (ⱖ60 mL/minute), multi-
ple regression analysis was performed using serum cre-
atinine. A high serum creatinine at 1 year (coefficient of
variance ⫺0.12, P ⬍ 0.001), but also current CNI-free
immunosuppression (coefficient of variance ⫺6.08, P ⬍
0.05) were associated with an annual fall in serum
creatinine in the univariate regression model, but not in
the multivariate regression model.
DISCUSSION
CKD in the posttransplantation setting is associated
with an increased mortality, with a relative risk of
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
4.55.9 Other than chronic kidney damage secondary to
CNIs used to prevent rejection, a multiplicity of other
factors have been suggested to play a role in the loss of
renal function in LT recipients.9,10 Loss of renal allo-
graft function due to infection with the BK polyomavi-
rus is emerging as a significant clinical problem in kid-
ney transplantation recipients.4,6,7 It is therefore
possible that BKV infection also plays a role in native
kidney dysfunction in recipients of solid organ trans-
plants other than the kidney. However, to date the po-
tential role of BKV infection in LT recipients has been
poorly investigated and data relies mainly on point-
prevalence studies of BKV infection with little or no
clinical correlatation.15-17,23
In the present study we demonstrated that BK viruria
is detectable in 24.4% of liver allograft recipients after
an average of 4.4 years (range, 1.8-7.1 years) following
transplantation, which is higher than previously re-
ported.15-17 However, in this series BK viruria is not
associated with BK viremia nor any other disease at-
tributable to BKV. There is therefore no at-risk popula-
tion in which to study whether active virus replication
of this order in LT recipients does or does not lead to
BKV nephropathy. Predictably, renal function and its
change over time in these patients were comparable to
LT recipients without detectable viral load in their urine
or blood. The strength of the present study is that renal
function was not only assessed using serum creatinine
at the time of viral studies, but that serial serum creat-

inine measurements from yearly follow-up were used to
assess changes of renal function over time. The preva-
lence rates of BK viruria in LT recipients demonstrated
thus far have been relatively low, with 13.5% in 37
patients by Splendiani et al.,23 7.8% in a series of 64
patients by Munoz et al.,16 and 15.9% in 44 patients by
Randhawa et al.15 In all 3 studies BK viremia was also
simultaneously investigated, but none of the BK viru-
ria–positive patients had BK viremia.15,16,23 BK viruria–
positive LT patients showed normal renal function in 1
study,23 whereas no correlation with kidney function
was attempted by Randhawa et al.15 In the third study,
1 in 5 LT recipients with BK viruria was reported to have
a serum creatinine ⬎132 ␮mol/L.
Although it has been shown that BK viruria is indic-
ative of viral replication and can be seen in up to 40% of
renal transplantation recipients, only the detection of
BKV in the renal biopsy by immunostaining with the
SV-40 antigen is indicative of viral replication, causing
disease in subjects with an appropriate clinical pic-
ture.7,8,19 It has been suggested that BKV nephropathy
can be diagnosed by plasma BKV-PCR,7,19 with a diag-
nostic sensitivity of 100% and a specificity of 88%.7
None of our BK viruria–positive LT recipients had pos-
itive plasma BKV-PCR and the same observation was
made in 2 other previous studies.15,16 In one series of
37 LT recipients, who were screened for BK viremia
within the first 18 months following transplantation, a
positive BKV PCR was found in 1 in 37 (2.7%) pa-
tients.17
Based on our results and findings by others, it ap-
pears that clinically significant BKV infection is an un-
common cause of renal dysfunction after LT. The ap-
parent increased susceptibility to BKV infection and
nephropathy in recipients of kidney transplantation,
but not in recipients of LT, could have several explana-
tions. First, BKV is known for its tropism for B-lympho-
cytes and for renal epithelial cells. It is therefore con-
ceivable that a different genomic strain of virus from the
donor is transmitted with the transplanted kidney, but
not when a different solid organ is engrafted, and this
could emerge as a new viral infection.24 Hence, BKV-
specific cytotoxic T cells in the host would be ineffective
in eradicating the new strain of BKV and this strain
could evade the immune system to cause BKV nephrop-
athy. Indeed, there is genomic heterogeneity of BKV,
giving rise to marked antigenic variability in the viral
capsid protein region.25,26 Second, stronger immuno-
suppression in renal transplantation recipients com-
pared to LT recipients would expose kidney transplan-
tation patients to a higher risk of significant BKV
infection. In fact, although the use of immunosuppres-
sive drugs is similar across the 2 groups of organ recip-
ients, target levels of CNIs are usually higher and the
rate of steroid withdrawal is usually lower in kidney
allograft recipients. BKV nephropathy in renal trans-
plants has been shown to be associated with stronger
immunosuppression, although no specific immuno-
suppressive drug or combination is associated with
BKV nephropathy.6,19,21,27 In our cohort there was no
significant difference in the type or intensity of immu-
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
BK VIRUS IN LIVER TRANSPLANTATION 1791
nosuppression between BK viruria–positive and BK
viruria–negative patients. Finally, viral replication in
renal allografts may be promoted by ischemic injury
occurring during the process of kidney transplantation
or by the occurrence of rejection episodes of the renal
allograft. In a prospective French study of 104 kidney
transplantation recipients, a cold ischemia duration of
over 24 hours was identified as a significant risk factor
for BK viruria,28 whereas in the study by Ramos et al.,20
34% of patients with biopsy-proven BKV nephropathy
had delayed graft function requiring dialysis. Nickeleit
et al.29 reported that all of the patients with late (range,
7-11 months) BKV infection of the renal allograft had a
complicated posttransplantation course with recurrent
rejection episodes.
There are some limitations to our study, which in-
clude the absence of follow-up sampling of patients
with BK viruria, the fact that quantitative PCR was not
performed, and the lack of renal biopsy specimens. The
threshold level for detection of viral DNA by PCR used
for BKV screening in this study was low. International
recommendations suggest that when the result of a
urine PCR is positive, it should either be confirmed by a
second positive result within 4 weeks or be followed by
specific quantitative diagnostic adjunctive assays with
threshold levels for presumptive disease such as a
urine DNA load of ⬎107 copies/mL or a plasma DNA
load of ⬎104 copies/mL.21 However, the lack of quan-
titative urine PCR in our patients with BK viruria is
balanced by the findings that none of those patients
had a positive plasma DNA load even at a lower number
of copies usually considered suggestive of nephropathy.
Because BKV nephropathy is unusual in the absence of
BK viremia,19 patients were offered the option of a renal
biopsy only if they tested positive for BK viremia and if
their kidney function showed a significant progressive
decrease, or it was otherwise clinically indicated. How-
ever, given the findings of absent BK viremia together
with comparable renal function and rate of decline in
GFR in LT recipients with and without BK viruria, we
can conclude that in this population the BK polyoma-
virus is an unlikely cause of significant clinical disease.
Finally, it is interesting to observe that none of the
patients with positive BK viruria had decoy cells in their
urine, and that 4 patients with decoy cells in their
urinary sediment had a negative urine or serum BKV
PCR. Decoy cells are not entirely sensitive or specific for
BKV infection. Moreover, decoy cells have been shown
not to necessarily correlate with biopsy-verified BK-
induced interstitial nephritis in renal transplant recip-
ients.7
CKD in this population of OLT recipients was com-
mon, with up to 10% of patients having severe CKD
(eGFR ⬍30 mL/minute/1.73 m2) after a median fol-
low-up of 6.3 (range, 4.9-7.4) years. A poor renal func-
tion at 1 year after transplantation was found to be
associated with an improvement in subsequent renal
function over time. This finding may reflect the effect of
dose reduction or withdrawal of CNI after the first year
posttransplantation. However, neither current renal
function nor decline in renal function were associated
1792 SALAMA ET AL.
with BK viruria or viremia in this LT population. Thus,
in the setting of established BKV reactivation, immuno-
suppression without kidney injury seems insufficient to
cause BK viremia and nephropathy, and it appears that
the most probable pathways for the development of
BKV nephropathy requires a second-hit, such as kid-
ney inflammation, kidney ischemia, or donor-recipient
human leukocyte antigen mismatch.
REFERENCES
1. Gardner SD, Field AM, Coleman DV, Hulme B. New hu-
man papovavirus (B.K.) isolated from urine after renal
transplantation. Lancet 1971;1:1253-1257.
2. Flaegstad T, Ronne K, Filipe AR, Traavik T. Prevalence of
anti BK virus antibody in Portugal and Norway. Scand
J Infect Dis 1989;21:145-147.
3. Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis
2003;3:611-623.
4. Randhawa PS, Finkelstein S, Scantlebury V, Shapiro R,
Vivas C, Jordan M, et al. Human polyoma virus-associated
interstitial nephritis in the allograft kidney. Transplanta-
tion 1999;67:103-109.
5. Peinemann F, de Villiers EM, Dorries K, Adams O, Vogeli
TA, Burdach S. Clinical course and treatment of haemor-
rhagic cystitis associated with BK type of human polyoma-
virus in nine paediatric recipients of allogeneic bone mar-
row transplants. Eur J Pediatr 2000;159:182-188.
6. Gardner SD, MacKenzie EF, Smith C, Porter AA. Prospec-
tive study of the human polyomaviruses BK and JC and
cytomegalovirus in renal transplant recipients. J Clin
Pathol 1984;37:578-586.
7. Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klim-
kait T, Mihatsch MJ, Steiger J. Prospective study of poly-
omavirus type BK replication and nephropathy in renal-
transplant recipients. N Engl J Med 2002;347:488-496.
8. Hirsch HH, Drachenberg CB, Steiger J, Ramos E. Poly-
omavirus-associated nephropathy in renal transplanta-
tion: critical issues of screening and management. Adv
Exp Med Biol 2006;577:160-173.
9. Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young
EW, et al. Chronic renal failure after transplantation of a
nonrenal organ. N Engl J Med 2003;349:931-940.
10. Pillebout E, Nochy D, Hill G, Conti F, Antoine C, Calmus Y,
Glotz D. Renal histopathological lesions after orthotopic
liver transplantation (OLT). Am J Transplant 2005;5:1120-
1129.
11. Barber CE, Hewlett TJ, Geldenhuys L, Kiberd BA, Acott
PD, Hatchette TF. BK virus nephropathy in a heart trans-
plant recipient: case report and review of the literature.
Transpl Infect Dis 2006;8:113-121.
12. Menahem SA, McDougall KM, Thomson NM, Dowling JP.
Native kidney BK nephropathy post cardiac transplanta-
tion. Transplantation 2005;79:259-260.
13. Schwarz A, Mengel M, Haller H, Niedermeyer J. Polyoma
virus nephropathy in native kidneys after lung transplan-
tation. Am J Transplant 2005;5:2582-2585.
14. Haririan A, Hamze O, Drachenberg CB, Ramos E, Weir
MR, Klassen DK. Polyomavirus reactivation in native kid-
neys of pancreas alone allograft recipients. Transplanta-
tion 2003;75:1186-1190.
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
15. Randhawa P, Uhrmacher J, Pasculle W, Vats A, Shapiro R,
Eghtsead B, Weck K. A comparative study of BK and JC
virus infections in organ transplant recipients. J Med Virol
2005;77:238-243.
16. Munoz P, Fogeda M, Bouza E, Verde E, Palomo J, Banares
R. Prevalence of BK virus replication among recipients of
solid organ transplants. Clin Infect Dis 2005;41:1720-
1725.
17. Puliyanda DP, Amet N, Dhawan A, Hilo L, Radha RK,
Bunnapradist S, et al. Isolated heart and liver transplant
recipients are at low risk for polyomavirus BKV nephrop-
athy. Clin Transplant 2006;20:289-294.
18. Razonable RR, Brown RA, Humar A, Covington E, Alecock
E, Paya CV. A longitudinal molecular surveillance study of
human polyomavirus viremia in heart, kidney, liver, and
pancreas transplant patients. J Infect Dis 2005;192:
1349-1354.
19. Nickeleit V, Klimkait T, Binet IF, Dalquen P, Del Zenero V,
Thiel G, et al. Testing for polyomavirus type BK DNA in
plasma to identify renal-allograft recipients with viral ne-
phropathy. N Engl J Med 2000;342:1309-1315.
20. Ramos E, Drachenberg CB, Papadimitriou JC, Hamze O,
Fink JC, Klassen DK, et al. Clinical course of polyoma
virus nephropathy in 67 renal transplant patients. J Am
Soc Nephrol 2002;13:2145-2151.
21. Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gor-
don J, Limaye AP, et al. Polyomavirus-associated ne-
phropathy in renal transplantation: interdisciplinary
analyses and recommendations. Transplantation 2005;
79:1277-1286.
22. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D.
A more accurate method to estimate glomerular filtration
rate from serum creatinine: a new prediction equation.
Modification of Diet in Renal Disease Study Group. Ann
Intern Med 1999;130:461-470.
23. Splendiani G, Cipriani S, Condo S, Paba P, Ciotti M,
Favalli C, et al. Polyoma virus BK and renal dysfunction in
a transplanted population. Transplant Proc 2004;36:713-
715.
24. Bohl DL, Storch GA, Ryschkewitsch C, Gaudreault-
Keener M, Schnitzler MA, Major EO, Brennan DC. Donor
origin of BK virus in renal transplantation and role of HLA
C7 in susceptibility to sustained BK viremia. Am J Trans-
plant 2005;5:2213-2221.
25. Dorries K. Molecular biology and pathogenesis of human
polyomavirus infections. Dev Biol Stand 1998;94:71-79.
26. Randhawa P, Zygmunt D, Shapiro R, Vats A, Weck K,
Swalsky P, Finkelstein S. Viral regulatory region sequence
variations in kidney tissue obtained from patients with BK
virus nephropathy. Kidney Int 2003;64:743-747.
27. Kwak EJ, Vilchez RA, Randhawa P, Shapiro R, Butel JS,
Kusne S. Pathogenesis and management of polyomavirus
infection in transplant recipients. Clin Infect Dis 2002;35:
1081-1087.
28. Bressollette-Bodin C, Coste-Burel M, Hourmant M, Sebille
V, Andre-Garnier E, Imbert-Marcille BM. A prospective
longitudinal study of BK virus infection in 104 renal trans-
plant recipients. Am J Transplant 2005;5:1926-1933.
29. Nickeleit V, Hirsch HH, Binet IF, Gudat F, Prince O,
Dalquen P, et al. Polyomavirus infection of renal allograft
recipients: from latent infection to manifest disease. J Am
Soc Nephrol 1999;10:1080-1089.