2 bk virus infection post renal transplant

Post renal transplant BK virus
infection

Dr. Sunil Kumar Daksh Parajapati

Introduction
 We will discuss today
 Polyoma virus infection, replication, and
disease in renal transplant recipients
 Treatment of PVAN (Polyoma virus
associated nephropathy)

Polyoma virus
 Five known human polyoma viruses
 BK & JC virus
 KI virus (KIPyV) & WU viruses (WUPyV)
were identiﬁed in 2007 from respiratory
secretions of a RTI pt.
 KI & WU viruses are named after the institutions
 In Jan 2008, Feng et al., identiﬁed Merkel cell
polyoma virus (MCPyV) was a/w Merkel cell
carcinoma

Transmission
 Occurs mostly through close contact
 Transmission through the feco-oral and
respiratory routes has been suggested
 Other routes include blood transfusion,
transplacentally, through semen, &organ
transplantation

BK virus infection
 Named after the first patient in which it was
described by Gardner (Sudanese kidney transplant
patient with ureteric stenosis whose initials were BK)
 Ubiquitous polyomavirus
 Acquired in childhood and becomes latent in
uroepithelial cells
 Reactivation of BK virus occurs in patients in
immunosuppressed states, including
 After transplantation
 HIV

Transplantation Proceedings 2008; 40: S48–51

BK virus infection
 Typically occurs during childhood, with
seroprevalence rates of 65% to 90% by the
age of 10 years, and is usually asymptomatic
 Individuals with altered immunity, however,
can experience high-level replication and may
present with urine cytology (“decoy” cells)

Transplantation Reviews 2008;22:241–51

Polyomavirus (BK)–associated
nephropathy (BKVN)
 Polyomavirus (BK)–associated
nephropathy (BKVN)
 Now recognized as significant problem in
renal transplants that may lead to progressive
allograft dysfunction
 First recognized in 1971 in adult renal
transplant recipients

Clinical manifestations
 Risk factors:
 Older, male, White, diabetic recipient
 More HLA mm, ACR, DGF
 Net state of immune suppression
 Seronegativity of the recipient
 lack of HLA-C7
 deceased donor transplantation
 Asymptomatic allograft dysfunction
 Prior tubular injury from rejection or drugs, surgical injury, warm
ischemia & reperfusion injury
 Suspect BK when rejection does not resolve with
usual therapy

Polyomavirus infection
 In renal transplant recipients,
 Polyomavirus-associated nephropathy
(PVAN) develops in 5% of patients and leads
to graft loss in approximately 50% of cases
 Pathogenesis of PVAN characterized by
 Persisting high-level polyoma BK virus (BKV)
replication in renal tubular epithelial cells,
inflammation, and progressive organ failure with
tubular atrophy and fibrosis


BK virus Nephropathy
 Polyoma virus: Renal transplant recipients
 Most cases of BKN occur within the first year
after kidney transplantation
 Definitive diagnosis requires histopathological
assessment, notably to exclude acute
rejection


BK virus Nephropathy
 BK viruria: 20% - 40% of renal transplant
patients
 BK viremia: approx. 12% of patients
 Studies have indicated that
 BK viremia greater than 10e4/mL is predictive of
definitive PVAN, and these patients should be
regarded as having “presumptive PVAN,” and
 Reduced immunosuppression should be
considered


BK Nephropathy

 Variable degree of
interstitial inflammation,
fibrosis, atrophy
 Similar in appearance to
cellular rejection
 Immunohistochemistry
useful

Since it has a patchy distribution affecting
mostly the medulla, two core biopsy
samples including medulla should be
obtained.

Polyomavirus infection
 BK nephropathy develops through three stages
 Stage A
 Few viral inclusion bodies and occasional positive
immunohistochemical staining, with an antibody to SV40
large T antigen that cross-reacts with BK large T antigen
 Stage B
 Fulminant nephropathy shows an inflammatory infiltrate with
focal tubulitis, which may mimic acute rejection but includes
prominent intranuclear inclusions and T-antigen staining
 Stage C
 Diffuse interstitial fibrosis and closely resembles chronic
allograft nephropathy

More recently..
 The use of electron microscopy to detect
cast-like, three dimensional polyoma virus
aggregates in urine called “Haufen” has
been found to be sensitive and speciﬁc for
BKVN.
 The positive and negative predictive values of
Haufen for BK polyoma virus nephropathy were
97% and 100%, respectively.

BK virus infection: Treatment
 The treatment of BKVN is unlikely to be
satisfactory until safe and effective
antiviral drugs are discovered
 Hence, there is a lot of current emphasis on
the prevention of this distressing complication

 Antiviral agents used empirically for BKVN
include
 Cidofovir
 Leflunomide,
 Quinolone antibiotics, and
 Intravenous immunoglobulin
 True efficacy of these strategies is unclear
because
 No randomized control trials have been done, and
the
 Value of therapy independent of reduction of
immunosuppression has not been specifically
evaluated Transplantation Reviews 2007;21:77–85

 Recent review “Treatment of polyomavirus
infection in kidney transplant recipients”
Conclusions
 There does not seem to be a graft survival
benefit of adding cidofovir or leflunomide to
immunosuppression reduction for the
management of PVAN
 However, the evidence base is poor and
highlights the urgent need for adequately
powered randomized trials to define the
optimal treatment of this important condition
Transplantation. 2010 May 15;89(9):1057-70.

 Currently,
 Reduction of immunosuppression remains the
most widely accepted approach to treatment
 It is now assumed that
 Screening all transplant patients with serial
PCR analyses of urine or serum, with
 Prompt reduction of immunosuppression when
patients initially display viruria or viremia, will
 Prevent or reduce the risk for developing BKVN

Transplantation Reviews 2010 ;24: 28–31

Reduction in immunosuppresion
 The most robust evidence supports
 Switch
 Tacrolimus to CsA (trough level 100–150 ng/mL)
 CsA/MMF to CsA/ steroids or tacrolimus/steroids
 Decrease
 Tacrolimus trough level to less than 6 ng/mL
 MMF dose to less than or equal to 1g/d
 CsA trough level to 100 to 150 ng/mL
 Conversion from MMF to an mTORinhibitor or
from tacrolimus/MMF to sirolimus/steroids is also
an option, but with fewer supportive data.

Two approaches

 Timely screening and adjustment in
immunosuppresion
 Identify patients at risk for BK infection and
use an immunosuppressive regimen from the
time of transplant that could be expected to
minimize risk.

 It is a medical and an ethical dilemma
 Whether retransplantation should be done
after a patient loses the renal graft to polyoma
nephropathy
 Should immunosuppressive therapy be
altered?
 Is nephroureterectomy of the failed graft
necessary?
 What is the natural course of the disease after
retransplantation?

 Retransplantation after polyomavirus-
associated nephropathy has been reported in 17
cases
 In these cases, recurrence of nephropathy has
occurred in 2 patients and viremia alone in a
third patient.
 For most of these patients, immunosuppression
after retransplantation was the same as for the
first transplantation
 Allograft nephrectomy was performed in 11 of the 15
patients

 Also, all 15 patients had reconstituted their
BKV-specific immune control, as
demonstrated by negative urine cytology
pretransplant
 Authors conclude that
 Retransplantation in patients without active
replication is generally safe


 Authors conclude that..
 Control of viral replication, allowing enough
time to raise sufficient immune response,
which usually requires more than 12 weeks of
reduced immunosuppression, appears to be a
desirable goal before a second transplant is
contemplated.
 In addition, nephroureterectomy is not
necessary when viral replication is absent
before retransplantation.

Conclusions
 BKV infections remain a significant concern in
kidney transplant patients

 Intensive viral monitoring and preemptive
adjustment of immunosuppression have led to
reduction in the incidence of overt viral
nephropathy

 Nonetheless, approximately 30% of patients in
major transplant programs develop viruria and
need to be carefully monitored for the possible
development of this complication

Conclusions
 In those patients who do develop BK Virus
induced allograft injury, we do not have reliable
antiviral drugs available at this time

 Although early diagnosis and prompt therapeutic
intervention have reduced rates of overt graft
loss to approximately 15%, surviving grafts
frequently show progressive decline in graft
function

Conclusions
 It is likely that long-term low-grade viruria and
viremia promote the development of chronic
allograft nephropathy

 The magnitude of this problem needs to be
clarified by future clinical studies.

2 bk virus infection post renal transplant

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (9)

Similar to 2 bk virus infection post renal transplant

Similar to 2 bk virus infection post renal transplant (20)

Recently uploaded

Recently uploaded (20)

2 bk virus infection post renal transplant