Abstracts
BK polyomavirus (BKPyV) is a causal agent of nephropathy, ureteral stenosis and hemorrhagic cystitis in kidney transplant recipients, and is considered an important emerging disease in transplantation. Regular screening for BKPyV reactivation mainly during the first 2 years posttransplant, with subsequent pre-emptive reduction of immunosuppression is considered the best option to avoid disease progression, since successful clearance or reduction of viremia is achieved in the vast majority of patients within 6 months. The use of drugs with antiviral properties for patients with persistent viremia has been attempted despite unclear benefits. Clinical manifestations of BKPyV nephropathy, current strategies for diagnosis and monitoring of BKPyV infection, management of immunosuppressive regimen after detection of BKPyV reactivation and the use of antiviral drugs are discussed in this review.
infection control; kidney transplantation; monitoring; review
BK Poliomavírus (BKPyV) é um agente causal de nefropatia, estenose ureteral e cistite hemorrágica em receptores de transplante renal, sendo considerado uma importante doença emergente na transplantação. Rastreamento regular para reativação do BKPyV, principalmente nos dois primeiros anos pós-transplante, com subsequente redução preemptiva da imunossupressão é considerada a melhor conduta para evitar a progressão da doença, já que a eliminação ou redução da viremia é alcançada na grande maioria dos pacientes dentro de 6 meses. O uso de drogas com propriedades antivirais para os pacientes com viremia persistente tem sido tentado, embora sem benefícios claros. As manifestações clínicas da nefropatia por BKPyV, as estratégias para o diagnóstico e monitoramento da infecção por BKPyV, o manejo do regime de imunossupressão após a detecção da reativação do BKPyV e o uso de drogas antivirais são discutidas nesta revisão.
controle de infecções; monitoramento; revisão; transplante de rim
Introduction
BK polyomavirus (BKPyV) belongs to the family Polyomaviridae (former
Papovaviridae) and are small (45-50 nm), nonenveloped virus with an
icosahedral capsid and a core of circular double-stranded DNA in association with
histones.11 Eash S, Manley K, Gasparovic M, Querbes W, Atwood WJ. The human
polyomaviruses. Cell Mol Life Sci 2006;63:865-76. PMID: 16501889 DOI:
http://dx.doi.org/10.1007/s00018-005-5454-z
http://dx.doi.org/10.1007/s00018-005-545...
,22 Krumbholz A, Bininda-Emonds OR, Wutzler P, Zell R. Phylogenetics,
evolution, and medical importance of polyomaviruses. Infect Genet Evol 2009;9:784-99.
DOI: http://dx.doi.org/10.1016/j.meegid.2009.04.008
http://dx.doi.org/10.1016/j.meegid.2009....
The virus was first isolated in 1971 and named after the initials
of a Sudanese transplant recipient with ureteral stenosis.33 van Aalderen MC, Heutinck KM, Huisman C, ten Berge IJ. BK virus
infection in transplant recipients: clinical manifestations, treatment options and
the immune response. Neth J Med 2012;70:172-83. PMID: 22641625
BKPyV is subdivided into four subtypes/serotypes: I, II, III, and IV. The geographic
distribution of the subtypes suggests a close relationship between BKPyV and migration
of human populations, although without any apparent clinical significance.44 Yogo Y, Sugimoto C, Zhong S, Homma Y. Evolution of the BK polyomavirus:
epidemiological, anthropological and clinical implications. Rev Med Virol
2009;19:185-99. DOI: http://dx.doi.org/10.1002/rmv.613
http://dx.doi.org/10.1002/rmv.613...
,55 Zhong S, Randhawa PS, Ikegaya H, Chen Q, Zheng HY, Suzuki M, et al.
Distribution patterns of BK polyomavirus (BKV) subtypes and subgroups in American,
European and Asian populations suggest co-migration of BKV and the human race. J Gen
Virol 2009;90:144-52. PMID: 19088283 DOI:
http://dx.doi.org/10.1099/vir.0.83611-0
http://dx.doi.org/10.1099/vir.0.83611-0...
BKPyV is ubiquitous in human population.66 White MK, Gordon J, Khalili K. The rapidly expanding family of human
polyomaviruses: recent developments in understanding their life cycle and role in
human pathology. PLoS Pathog 2013;9:e1003206. DOI:
http://dx.doi.org/10.1371/journal.ppat.1003206
http://dx.doi.org/10.1371/journal.ppat.1...
Primary
infection occurs in the first decade of life as evidenced by increases in BKPyV
seroprevalence to 90% and more.77 Knowles WA, Pipkin P, Andrews N, Vyse A, Minor P, Brown DW, et al.
Population-based study of antibody to the human polyomaviruses BKV and JCV and the
simian polyomavirus SV40. J Med Virol 2003;71:115-23. PMID: 12858417 DOI:
http://dx.doi.org/10.1002/jmv.10450
http://dx.doi.org/10.1002/jmv.10450...
Natural BKPyV
transmission is not clear, but likely occurs via the respiratory or oral route. Primary
infection in healthy children is usually asymptomatic, but may manifest as a common
cold.88 Jiang M, Abend JR, Johnson SF, Imperiale MJ. The role of polyomaviruses
in human disease. Virology 2009;20:266-73. DOI:
http://dx.doi.org/10.1016/j.virol.2008.09.027
http://dx.doi.org/10.1016/j.virol.2008.0...
After primary viremia, the virus
establishes a latent phase, persisting indefinitely in different tissues, especially the
urinary tract.22 Krumbholz A, Bininda-Emonds OR, Wutzler P, Zell R. Phylogenetics,
evolution, and medical importance of polyomaviruses. Infect Genet Evol 2009;9:784-99.
DOI: http://dx.doi.org/10.1016/j.meegid.2009.04.008
http://dx.doi.org/10.1016/j.meegid.2009....
,99 Nickeleit V, Hirsch HH, Zeiler M, Gudat F, Prince O, Thiel G, et al.
BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression
and rejection in a puzzling game. Nephrol Dial Transplant 2000;15:324-32. DOI:
http://dx.doi.org/10.1093/ndt/15.3.324
http://dx.doi.org/10.1093/ndt/15.3.324...
In approximately 5% to 10% of healthy individuals, BKPyV reactivates with variations in
immune status and gives asymptomatic low-level urinary shedding.1010 Dharnidharka VR, Abdulnour HA, Araya CE. The BK virus in renal
transplant recipients-review of pathogenesis, diagnosis, and treatment. Pediatr
Nephrol 2011;26:1763-74. DOI:
http://dx.doi.org/10.1007/s00467-010-1716-6
http://dx.doi.org/10.1007/s00467-010-171...
However, no histopathological changes are observed in the kidney
parenchyma, and renal function is left unaffected.11 Eash S, Manley K, Gasparovic M, Querbes W, Atwood WJ. The human
polyomaviruses. Cell Mol Life Sci 2006;63:865-76. PMID: 16501889 DOI:
http://dx.doi.org/10.1007/s00018-005-5454-z
http://dx.doi.org/10.1007/s00018-005-545...
Clinical manifestations
Replication of BKPyV occurs during states of immune suppression. Viruria occurs in
pregnancy, cancer, HIV infection, diabetes, and transplantation. However, viremia and
BKPyV nephropathy (BKVN) are rare outside of kidney transplantation.1111 Bohl DL, Brennan DC. BK virus nephropathy and kidney transplantation.
Clin J Am Soc Nephrol 2007;2:S36-46. DOI:
http://dx.doi.org/10.2215/CJN.00920207
http://dx.doi.org/10.2215/CJN.00920207...
Apart from immune status, other variables such as
older age, male gender, white ethnicity, diabetes, BKPyV seronegativity prior to
transplantation, immunosuppressive drug regimen, ischemic lesion during transplantation
and viral mutations, are considered risk factors for BK disease.1212 Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP,
et al. Polyomavirus-associated nephropathy in renal transplantation:
interdisciplinary analyses and recommendations. Transplantation 2005;79:1277-86.
PMID: 15912088 DOI:
http://dx.doi.org/10.1097/01.TP.0000156165.83160.09
http://dx.doi.org/10.1097/01.TP.00001561...
BKPyV infections in immunosuppressed individuals can lead to distinctive pathological
entities in different patient groups: in renal transplant recipients, it is associated
with nephropathy and ureteral stenosis, whereas in hematopoietic stem cell transplant
(HSCT) recipients with hemorrhagic cystitis.22 Krumbholz A, Bininda-Emonds OR, Wutzler P, Zell R. Phylogenetics,
evolution, and medical importance of polyomaviruses. Infect Genet Evol 2009;9:784-99.
DOI: http://dx.doi.org/10.1016/j.meegid.2009.04.008
http://dx.doi.org/10.1016/j.meegid.2009....
,88 Jiang M, Abend JR, Johnson SF, Imperiale MJ. The role of polyomaviruses
in human disease. Virology 2009;20:266-73. DOI:
http://dx.doi.org/10.1016/j.virol.2008.09.027
http://dx.doi.org/10.1016/j.virol.2008.0...
,1212 Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP,
et al. Polyomavirus-associated nephropathy in renal transplantation:
interdisciplinary analyses and recommendations. Transplantation 2005;79:1277-86.
PMID: 15912088 DOI:
http://dx.doi.org/10.1097/01.TP.0000156165.83160.09
http://dx.doi.org/10.1097/01.TP.00001561...
BKVN is the result of viral replication in renal tissue, and is characterized by a
histologically manifest renal allograft infection with BKPyV and deteriorating graft
function. The gold standard for BKVN is still a renal biopsy.1010 Dharnidharka VR, Abdulnour HA, Araya CE. The BK virus in renal
transplant recipients-review of pathogenesis, diagnosis, and treatment. Pediatr
Nephrol 2011;26:1763-74. DOI:
http://dx.doi.org/10.1007/s00467-010-1716-6
http://dx.doi.org/10.1007/s00467-010-171...
Since it has a patchy distribution affecting mostly the renal
medulla,1313 Drachenberg CB, Hirsch HH, Ramos E, Papadimitriou JC. Polyomavirus
disease in renal transplantation: review of pathological findings and diagnostic
methods. Hum Pathol 2005;36:1245-55. PMID: 16311117 two core biopsy samples including
medulla should be obtained in order to confirm the BKPyV presence by in
situ hybridization or immunohistochemistry for anti-SV40 or large T.1212 Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP,
et al. Polyomavirus-associated nephropathy in renal transplantation:
interdisciplinary analyses and recommendations. Transplantation 2005;79:1277-86.
PMID: 15912088 DOI:
http://dx.doi.org/10.1097/01.TP.0000156165.83160.09
http://dx.doi.org/10.1097/01.TP.00001561...
The histologic patterns of BKVN have been divided
into three types, being characterized by the presence of nuclear inclusions (Type A),
acute inflammation with little chronic fibrosis (Type B), and significant chronic
fibrosis and atrophy (Type C).1414 Nickeleit V, Mihatsch MJ. Polyomavirus nephropathy in native kidneys and
renal allografts: an update on an escalating threat. Transpl Int 2006;19:960-73. DOI:
http://dx.doi.org/10.1111/j.1432-2277.2006.00360.x
http://dx.doi.org/10.1111/j.1432-2277.20...
In 25-40% of the
patients experiencing high level viruria/decoy cell positivity will develop viremia, and
in the absence of intervention, progression to BKVN may occur.1010 Dharnidharka VR, Abdulnour HA, Araya CE. The BK virus in renal
transplant recipients-review of pathogenesis, diagnosis, and treatment. Pediatr
Nephrol 2011;26:1763-74. DOI:
http://dx.doi.org/10.1007/s00467-010-1716-6
http://dx.doi.org/10.1007/s00467-010-171...
The prevalence of BKVN may vary from center to center, but
generally ranges from 1% to 10% and the result is the graft loss in up to 80% of
cases.1212 Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP,
et al. Polyomavirus-associated nephropathy in renal transplantation:
interdisciplinary analyses and recommendations. Transplantation 2005;79:1277-86.
PMID: 15912088 DOI:
http://dx.doi.org/10.1097/01.TP.0000156165.83160.09
http://dx.doi.org/10.1097/01.TP.00001561...
,1515 Zalona AC, Varella RB, Takiya CM, Goncalves RT, Zalis MG, Santoro-Lopes
G. A qualitative seminested PCR assay as an alternative to urine cytology for BK
polyomavirus screening after renal transplantation. Intervirology 2013;56:249-52.
DOI: http://dx.doi.org/10.1159/000349896
http://dx.doi.org/10.1159/000349896...
Its noteworthy that nephropathy can also be caused by another
polyomavirus named JC in rare cases, which demands additional investigation in the event
of nephropathy without BKPyV detection.1616 Drachenberg CB, Hirsch HH, Papadimitriou JC, Gosert R, Wali RK,
Munivenkatappa R, et al. Polyomavirus BK versus JC replication and nephropathy in
renal transplant recipients: a prospective evaluation. Transplantation
2007;84:323-30. PMID: 17700156 DOI:
http://dx.doi.org/10.1097/01.tp.0000269706.59977.a5
http://dx.doi.org/10.1097/01.tp.00002697...
Hemorrhagic cystitis (HC) is the most common BKPyV manifestation of genitourinary infection in HSCT recipients. The virally induced form of HC usually occurs after engraftment and is therefore referred to as late-onset hemorrhagic cystitis, which occurs in 6 to 29% of HSCT patients, generally within the first two months after transplantation. Patients present with hematuria, painful voiding, bladder cramps, and/or flank pain.33 van Aalderen MC, Heutinck KM, Huisman C, ten Berge IJ. BK virus infection in transplant recipients: clinical manifestations, treatment options and the immune response. Neth J Med 2012;70:172-83. PMID: 22641625
The ureteral stenosis occurs in approximately 3% (2-6% range) of renal transplant
patients and generally develops several months after transplantation.33 van Aalderen MC, Heutinck KM, Huisman C, ten Berge IJ. BK virus
infection in transplant recipients: clinical manifestations, treatment options and
the immune response. Neth J Med 2012;70:172-83. PMID: 22641625 The virus may exert a direct cytopathic effect on
the ureteral epithelium, resulting in ulceration and inflammation, which leads to
obstructive uropathy.1717 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;35:1081-7. PMID: 12384842 DOI:
http://dx.doi.org/10.1086/344060
http://dx.doi.org/10.1086/344060...
In addition, BKPyV is also possibly related to pneumonia, encephalitis and several types
of cancer.1818 Dalianis T, Hirsch HH. Human polyomaviruses in disease and cancer.
Virology 2013;437:63-72. DOI:
http://dx.doi.org/10.1016/j.virol.2012.12.015
http://dx.doi.org/10.1016/j.virol.2012.1...
These non-urinary BKPyV-induced
diseases are not surprising at all given the viral persistence in different human
tissues and the oncogenic potential of polyomaviruses.1919 Moens U, Ludvigsen M, Van Ghelue M. Human polyomaviruses in skin
diseases. Patholog Res Int 2011;2011:123491.PMID: 21941687,2020 DeCaprio JA, Garcea RL. A cornucopia of human polyomaviruses. Nat Rev
Microbiol 2013;11:264-76. DOI: http://dx.doi.org/10.1038/nrmicro2992
http://dx.doi.org/10.1038/nrmicro2992...
Methods for BKPYV screening in urine and blood
The methods used to detect and quantify BKPyV are based on the pathogenesis of the
infection.1111 Bohl DL, Brennan DC. BK virus nephropathy and kidney transplantation.
Clin J Am Soc Nephrol 2007;2:S36-46. DOI:
http://dx.doi.org/10.2215/CJN.00920207
http://dx.doi.org/10.2215/CJN.00920207...
Viral replication begins early
after transplantation and progresses through detectable stages: viruria to viremia and
then to nephropathy (Figure 1). The onset for each
event is variable: viruria is usually reported ≥ 5 weeks after transplantation, followed
by viremia after 4-5 weeks,2121 Renoult E, Coutlée F, Pâquet M, St Louis G, Girardin C, Fortin MC, et
al. Evaluation of a preemptive strategy for BK polyomavirus-associated nephropathy
based on prospective monitoring of BK viremia: a kidney transplantation center
experience. Transplant Proc 2010;42:4083-7. PMID: 21168633 DOI:
http://dx.doi.org/10.1016/j.transproceed.2010.09.024
http://dx.doi.org/10.1016/j.transproceed...
,2222 Chakera A, Dyar OJ, Hughes E, Bennett S, Hughes D, Roberts IS. Detection
of polyomavirus BK reactivation after renal transplantation using an intensive decoy
cell surveillance program is cost-effective. Transplantation 2011;92:1018-23. PMID:
21946172 which in turn precedes BKVN in 8-12 weeks.2323 Laskin BL, Goebel J. Cost-efficient screening for BK virus in pediatric
kidney transplantation: a single-center experience and review of the literature.
Pediatr Transplant 2010;14:589-95. DOI:
http://dx.doi.org/10.1111/j.1399-3046.2010.01318.x
http://dx.doi.org/10.1111/j.1399-3046.20...
,2424 Alméras C, Vetromile F, Garrigue V, Szwarc I, Foulongne V, Mourad G.
Monthly screening for BK viremia is an effective strategy to prevent BK virus
nephropathy in renal transplant recipients. Transpl Infect Dis 2011;13:101-8. DOI:
http://dx.doi.org/10.1111/j.1399-3062.2011.00619.x
http://dx.doi.org/10.1111/j.1399-3062.20...
In general, viruria-based methods are considered valuable tools for BKPyV screening
(high negative predictive value, NPV) but weakly indicative of kidney or urinary tract
diseases (low positive predictive value, PPV), since less than a half of all patients
with viruria will progress to the viremia stage.2525 Drachenberg CB, Papadimitriou JC, Ramos E. Histologic versus molecular
diagnosis of BK polyomavirus-associated nephropathy: a shifting paradigm? Clin J Am
Soc Nephrol 2006;1:374-9. Three methods are available for BKPyV viruria screening: urine
cytopathology ("decoy cells"), DNA detection/ quantification, and electronic microscopy
"Haufen" bodies.2626 Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK
polyomavirus in solid organ transplantation. Am J Transplant 2013;13:179-88. DOI:
http://dx.doi.org/10.1111/ajt.12110
http://dx.doi.org/10.1111/ajt.12110...
Decoy cells are epithelial cells with enlarged nuclei and large basophilic ground-glass
intranuclear inclusions.99 Nickeleit V, Hirsch HH, Zeiler M, Gudat F, Prince O, Thiel G, et al.
BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression
and rejection in a puzzling game. Nephrol Dial Transplant 2000;15:324-32. DOI:
http://dx.doi.org/10.1093/ndt/15.3.324
http://dx.doi.org/10.1093/ndt/15.3.324...
Although one decoy cell
is sufficient to mark the activation of polyomaviruses, in clinical practice an
arbitrary threshold level of more than 10 decoy cells per liquid-based cytology
preparation has been set to distinguish 'decoy positive' from 'decoy negative'
patients.1414 Nickeleit V, Mihatsch MJ. Polyomavirus nephropathy in native kidneys and
renal allografts: an update on an escalating threat. Transpl Int 2006;19:960-73. DOI:
http://dx.doi.org/10.1111/j.1432-2277.2006.00360.x
http://dx.doi.org/10.1111/j.1432-2277.20...
Decoy cell can be easily detected
in standard Papanicolaou-stained cytology preparations and is considered a cost-saving
technique without the cross-contamination risks of PCR-based methodologies.2222 Chakera A, Dyar OJ, Hughes E, Bennett S, Hughes D, Roberts IS. Detection
of polyomavirus BK reactivation after renal transplantation using an intensive decoy
cell surveillance program is cost-effective. Transplantation 2011;92:1018-23. PMID:
21946172 Also the NPV of decoy cells approximates
100%.2626 Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK
polyomavirus in solid organ transplantation. Am J Transplant 2013;13:179-88. DOI:
http://dx.doi.org/10.1111/ajt.12110
http://dx.doi.org/10.1111/ajt.12110...
On the other hand, the PPV of decoy
cell analysis to predict BKVN is only 25 to 30%; cytology results are more susceptible
to delays in processing and shipment of samples; and require a trained cytologist.1515 Zalona AC, Varella RB, Takiya CM, Goncalves RT, Zalis MG, Santoro-Lopes
G. A qualitative seminested PCR assay as an alternative to urine cytology for BK
polyomavirus screening after renal transplantation. Intervirology 2013;56:249-52.
DOI: http://dx.doi.org/10.1159/000349896
http://dx.doi.org/10.1159/000349896...
Nevertheless, due to its high cost-effectiveness,
the use of decoy cell remains solid in several diagnostic centers.
Electronic microscopy methods are based on the detection of viral particles or "Haufen",
defined as discrete, tightly clustered, cast-like aggregates of a minimum of six
polyomaviruses with an unequivocal three-dimensional architecture.2727 Singh HK, Andreoni KA, Madden V, True K, Detwiler R, Weck K, et al.
Presence of urinary Haufen accurately predicts polyomavirus nephropathy. J Am Soc
Nephrol 2009;20:416-27. DOI:
http://dx.doi.org/10.1681/ASN.2008010117
http://dx.doi.org/10.1681/ASN.2008010117...
Positive and negative predictive values of Haufen for BKVN are
very high, reaching > 90%,2626 Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK
polyomavirus in solid organ transplantation. Am J Transplant 2013;13:179-88. DOI:
http://dx.doi.org/10.1111/ajt.12110
http://dx.doi.org/10.1111/ajt.12110...
and may serve as a
noninvasive means to diagnose BKVN in the urine.2828 Westervelt JD, Alexander BD, Costa SF, Miller SE, Howell DN, Smith SR.
Detection of BK polyomavirus after kidney transplantation: a comparison of urine
electron microscopy with plasma polymerase chain reaction. Clin Transplant
2013;27:E42-8. DOI: http://dx.doi.org/10.1111/ctr.12048
http://dx.doi.org/10.1111/ctr.12048...
However, the costs required to perform routine electronic microscopy is
prohibitive for most diagnostic centers.
PCR-based methodologies for DNA detection/quantification in urine or blood have been
considered the method of choice by current guidelines. Quantitative PCR (qPCR) is
equivalent to decoy cytology to estimate BKPyV viruria and viral loads > 7
log10 copies/ml are considered significant.2626 Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK
polyomavirus in solid organ transplantation. Am J Transplant 2013;13:179-88. DOI:
http://dx.doi.org/10.1111/ajt.12110
http://dx.doi.org/10.1111/ajt.12110...
The advantages of testing BKPyV viruria are similar to decoy: high NPV for
BKVN; precedes viremia ≥ 4 weeks,2424 Alméras C, Vetromile F, Garrigue V, Szwarc I, Foulongne V, Mourad G.
Monthly screening for BK viremia is an effective strategy to prevent BK virus
nephropathy in renal transplant recipients. Transpl Infect Dis 2011;13:101-8. DOI:
http://dx.doi.org/10.1111/j.1399-3062.2011.00619.x
http://dx.doi.org/10.1111/j.1399-3062.20...
which works
as a warning sign to viremia; and is a non-invasive technique. In addition, BKVN with
detectable viruria without viremia has been reported.2323 Laskin BL, Goebel J. Cost-efficient screening for BK virus in pediatric
kidney transplantation: a single-center experience and review of the literature.
Pediatr Transplant 2010;14:589-95. DOI:
http://dx.doi.org/10.1111/j.1399-3046.2010.01318.x
http://dx.doi.org/10.1111/j.1399-3046.20...
Nonetheless, factors such as low PPV for BKVN, costs involved in qPCR,
lack of standardization and natural fluctuation of BKPyV loads in urine, can be
considerable disadvantages.2626 Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK
polyomavirus in solid organ transplantation. Am J Transplant 2013;13:179-88. DOI:
http://dx.doi.org/10.1111/ajt.12110
http://dx.doi.org/10.1111/ajt.12110...
BKPyV viremia, on the other hand, is universally considered the single most important
parameter to predict BKVN,1010 Dharnidharka VR, Abdulnour HA, Araya CE. The BK virus in renal
transplant recipients-review of pathogenesis, diagnosis, and treatment. Pediatr
Nephrol 2011;26:1763-74. DOI:
http://dx.doi.org/10.1007/s00467-010-1716-6
http://dx.doi.org/10.1007/s00467-010-171...
,2323 Laskin BL, Goebel J. Cost-efficient screening for BK virus in pediatric
kidney transplantation: a single-center experience and review of the literature.
Pediatr Transplant 2010;14:589-95. DOI:
http://dx.doi.org/10.1111/j.1399-3046.2010.01318.x
http://dx.doi.org/10.1111/j.1399-3046.20...
,2626 Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK
polyomavirus in solid organ transplantation. Am J Transplant 2013;13:179-88. DOI:
http://dx.doi.org/10.1111/ajt.12110
http://dx.doi.org/10.1111/ajt.12110...
reaching a PPV ≥ 90% and a sensitivity of 93% in persistently high BKV DNA
loads (> 104 copies/ml). However, a viral load < 4 log10
copies/ml does not completely rule out BKVN, and deserves continuous monitoring.2828 Westervelt JD, Alexander BD, Costa SF, Miller SE, Howell DN, Smith SR.
Detection of BK polyomavirus after kidney transplantation: a comparison of urine
electron microscopy with plasma polymerase chain reaction. Clin Transplant
2013;27:E42-8. DOI: http://dx.doi.org/10.1111/ctr.12048
http://dx.doi.org/10.1111/ctr.12048...
The optimal threshold of BKPyV DNAnemia is not
standardized, and values expressed in copies/ml > 500;2828 Westervelt JD, Alexander BD, Costa SF, Miller SE, Howell DN, Smith SR.
Detection of BK polyomavirus after kidney transplantation: a comparison of urine
electron microscopy with plasma polymerase chain reaction. Clin Transplant
2013;27:E42-8. DOI: http://dx.doi.org/10.1111/ctr.12048
http://dx.doi.org/10.1111/ctr.12048...
> 600;2222 Chakera A, Dyar OJ, Hughes E, Bennett S, Hughes D, Roberts IS. Detection
of polyomavirus BK reactivation after renal transplantation using an intensive decoy
cell surveillance program is cost-effective. Transplantation 2011;92:1018-23. PMID:
21946172 > 750;2929 Knight RJ, Gaber LW, Patel SJ, DeVos JM, Moore LW, Gaber AO. Screening
for BK viremia reduces but does not eliminate the risk of BK nephropathy: a
single-center retrospective analysis. Transplantation 2013;95:949-54. DOI:
http://dx.doi.org/10.1097/TP.0b013e31828423cd
http://dx.doi.org/10.1097/TP.0b013e31828...
and > 1,000,3030 Drachenberg C, Hirsch HH, Papadimitriou JC, Mozafari P, Wali R, McKinney
JD, et al. Cost efficiency in the prospective diagnosis and follow-up of polyomavirus
allograft nephropathy. Transplant Proc 2004;36:3028-31. PMID: 15686687 DOI:
http://dx.doi.org/10.1016/j.transproceed.2004.10.045
http://dx.doi.org/10.1016/j.transproceed...
have been considered significant. Given its overall performance, BKPyV
viremia testing without urine became the method of choice in many diagnostic centers and
also recommended by the KDIGO Transplant Work Group in 2009,3131 Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group.
KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J
Transplant 2009;9:S1-155. although viruria screening prior to viremia quantitation is
considered cost-saving.2222 Chakera A, Dyar OJ, Hughes E, Bennett S, Hughes D, Roberts IS. Detection
of polyomavirus BK reactivation after renal transplantation using an intensive decoy
cell surveillance program is cost-effective. Transplantation 2011;92:1018-23. PMID:
21946172
Current strategies for diagnosis and monitoring of BKPYV infection
BKVN is predominant (> 90%) in the first two years of transplantation, especially in
the first trimester.2424 Alméras C, Vetromile F, Garrigue V, Szwarc I, Foulongne V, Mourad G.
Monthly screening for BK viremia is an effective strategy to prevent BK virus
nephropathy in renal transplant recipients. Transpl Infect Dis 2011;13:101-8. DOI:
http://dx.doi.org/10.1111/j.1399-3062.2011.00619.x
http://dx.doi.org/10.1111/j.1399-3062.20...
Screening efforts have
mainly been focusing on the first 6-12 months. However, due to the precocity of BKPyV
viremia in most cases, the tendency has been driven for condensed screening in the first
months.
Current screening strategies relies on two basic principles: 1) viruria followed by viremia; 2) viremia only. Despite methodological variations, both strategies showed to be equally effective in detecting BKPyV infection, allowing for timely intervention.
Strategy 1: viruria followed by viremia
As previously mentioned, viruria can be assessed by electronic microscopy, decoy
cytology and qPCR. However, performing these techniques simultaneously seems do not
add useful clinical information.3030 Drachenberg C, Hirsch HH, Papadimitriou JC, Mozafari P, Wali R, McKinney
JD, et al. Cost efficiency in the prospective diagnosis and follow-up of polyomavirus
allograft nephropathy. Transplant Proc 2004;36:3028-31. PMID: 15686687 DOI:
http://dx.doi.org/10.1016/j.transproceed.2004.10.045
http://dx.doi.org/10.1016/j.transproceed...
Current
strategies indicate that viruria testing should be performed biweekly during the
first three months. After, it will be performed monthly until the sixth month. Then,
every 2 or 3 months until 2 years post-transplant, and anytime during any allograft
dysfunction.1111 Bohl DL, Brennan DC. BK virus nephropathy and kidney transplantation.
Clin J Am Soc Nephrol 2007;2:S36-46. DOI:
http://dx.doi.org/10.2215/CJN.00920207
http://dx.doi.org/10.2215/CJN.00920207...
,2222 Chakera A, Dyar OJ, Hughes E, Bennett S, Hughes D, Roberts IS. Detection
of polyomavirus BK reactivation after renal transplantation using an intensive decoy
cell surveillance program is cost-effective. Transplantation 2011;92:1018-23. PMID:
21946172,2626 Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK
polyomavirus in solid organ transplantation. Am J Transplant 2013;13:179-88. DOI:
http://dx.doi.org/10.1111/ajt.12110
http://dx.doi.org/10.1111/ajt.12110...
Nevertheless, monthly or quarterly (less frequent) screening up to 2
years post-transplant is still employed for urine BKPyV search.1010 Dharnidharka VR, Abdulnour HA, Araya CE. The BK virus in renal
transplant recipients-review of pathogenesis, diagnosis, and treatment. Pediatr
Nephrol 2011;26:1763-74. DOI:
http://dx.doi.org/10.1007/s00467-010-1716-6
http://dx.doi.org/10.1007/s00467-010-171...
Decoy cell cytology and qPCR are the most used procedures,
although cost-effectiveness favors the former.2222 Chakera A, Dyar OJ, Hughes E, Bennett S, Hughes D, Roberts IS. Detection
of polyomavirus BK reactivation after renal transplantation using an intensive decoy
cell surveillance program is cost-effective. Transplantation 2011;92:1018-23. PMID:
21946172 Despite the low clinical significance of isolated viruria, the
maintenance of high BKPyV loads in urine (> 7 log10 copies/ml) or
sustained decoy positivity (defined as ≥ 2 positive samples > 2 weeks apart) is a
strong indicative of future viremia (75%) and BKVN. Quantitative measurement of
viremia is not indicated in patients without viruria.3030 Drachenberg C, Hirsch HH, Papadimitriou JC, Mozafari P, Wali R, McKinney
JD, et al. Cost efficiency in the prospective diagnosis and follow-up of polyomavirus
allograft nephropathy. Transplant Proc 2004;36:3028-31. PMID: 15686687 DOI:
http://dx.doi.org/10.1016/j.transproceed.2004.10.045
http://dx.doi.org/10.1016/j.transproceed...
However, in case of positive detection of BKPyV in urine by the
aforesaid procedures, viremia testing should be performed.
Strategy 2: viremia screening
The guidelines suggest reducing immunosuppressive medications when BKPyV plasma is
persistently greater than 10,000 copies/ml,3030 Drachenberg C, Hirsch HH, Papadimitriou JC, Mozafari P, Wali R, McKinney
JD, et al. Cost efficiency in the prospective diagnosis and follow-up of polyomavirus
allograft nephropathy. Transplant Proc 2004;36:3028-31. PMID: 15686687 DOI:
http://dx.doi.org/10.1016/j.transproceed.2004.10.045
http://dx.doi.org/10.1016/j.transproceed...
and the diagnosis of "presumptive BKVAN" should be made.1212 Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP,
et al. Polyomavirus-associated nephropathy in renal transplantation:
interdisciplinary analyses and recommendations. Transplantation 2005;79:1277-86.
PMID: 15912088 DOI:
http://dx.doi.org/10.1097/01.TP.0000156165.83160.09
http://dx.doi.org/10.1097/01.TP.00001561...
Most of the current BKPyV screening procedures are focused on
viremia only, without the support of viruria. In both cases immunosuppression
reduction is recommended even in the absence of BKPyV in biopsy (see ref. 26 for
details). The term "sustained" or "persistent" is defined as two or more consecutive
positive plasma samples (over ≥ 2-3 weeks). However, different groups also recommend
immunosuppression reduction after sustained2121 Renoult E, Coutlée F, Pâquet M, St Louis G, Girardin C, Fortin MC, et
al. Evaluation of a preemptive strategy for BK polyomavirus-associated nephropathy
based on prospective monitoring of BK viremia: a kidney transplantation center
experience. Transplant Proc 2010;42:4083-7. PMID: 21168633 DOI:
http://dx.doi.org/10.1016/j.transproceed.2010.09.024
http://dx.doi.org/10.1016/j.transproceed...
,2929 Knight RJ, Gaber LW, Patel SJ, DeVos JM, Moore LW, Gaber AO. Screening
for BK viremia reduces but does not eliminate the risk of BK nephropathy: a
single-center retrospective analysis. Transplantation 2013;95:949-54. DOI:
http://dx.doi.org/10.1097/TP.0b013e31828423cd
http://dx.doi.org/10.1097/TP.0b013e31828...
or a single low
level (≈ 1,000 copies/ml) viremia.2424 Alméras C, Vetromile F, Garrigue V, Szwarc I, Foulongne V, Mourad G.
Monthly screening for BK viremia is an effective strategy to prevent BK virus
nephropathy in renal transplant recipients. Transpl Infect Dis 2011;13:101-8. DOI:
http://dx.doi.org/10.1111/j.1399-3062.2011.00619.x
http://dx.doi.org/10.1111/j.1399-3062.20...
,2828 Westervelt JD, Alexander BD, Costa SF, Miller SE, Howell DN, Smith SR.
Detection of BK polyomavirus after kidney transplantation: a comparison of urine
electron microscopy with plasma polymerase chain reaction. Clin Transplant
2013;27:E42-8. DOI: http://dx.doi.org/10.1111/ctr.12048
http://dx.doi.org/10.1111/ctr.12048...
Monthly testing in
the first 6-12 months followed by three months intervals is being widely adopted.
Clinical management
Currently, reduction of immunossupression is the keystone of therapy for BKVN. Since
late diagnosis of BKVN is usually associated with an irreversible decline of graft
function3232 Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ,
et al. Prospective study of polyomavirus type BK replication and nephropathy in
renal-transplant recipients. N Engl J Med 2002;347:488-96. PMID: 12181403 DOI:
http://dx.doi.org/10.1056/NEJMoa020439
http://dx.doi.org/10.1056/NEJMoa020439...
,3333 Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA, Cohen EP. BK
virus nephritis: risk factors, timing, and outcome in renal transplant recipients.
Kidney Int 2005;68:1834-9. PMID: 16164661 DOI:
http://dx.doi.org/10.1111/j.1523-1755.2005.00602.x
http://dx.doi.org/10.1111/j.1523-1755.20...
and most of patients with viremia will eventually develop BKVN,
regular screening for BKPyV reactivation, mainly during the first 2 years
posttransplant, with subsequent pre-emptive reduction of immunosuppression is the usual
procedure adopted by transplant centers.2121 Renoult E, Coutlée F, Pâquet M, St Louis G, Girardin C, Fortin MC, et
al. Evaluation of a preemptive strategy for BK polyomavirus-associated nephropathy
based on prospective monitoring of BK viremia: a kidney transplantation center
experience. Transplant Proc 2010;42:4083-7. PMID: 21168633 DOI:
http://dx.doi.org/10.1016/j.transproceed.2010.09.024
http://dx.doi.org/10.1016/j.transproceed...
22 Chakera A, Dyar OJ, Hughes E, Bennett S, Hughes D, Roberts IS. Detection
of polyomavirus BK reactivation after renal transplantation using an intensive decoy
cell surveillance program is cost-effective. Transplantation 2011;92:1018-23. PMID:
21946172
23 Laskin BL, Goebel J. Cost-efficient screening for BK virus in pediatric
kidney transplantation: a single-center experience and review of the literature.
Pediatr Transplant 2010;14:589-95. DOI:
http://dx.doi.org/10.1111/j.1399-3046.2010.01318.x
http://dx.doi.org/10.1111/j.1399-3046.20...
24 Alméras C, Vetromile F, Garrigue V, Szwarc I, Foulongne V, Mourad G.
Monthly screening for BK viremia is an effective strategy to prevent BK virus
nephropathy in renal transplant recipients. Transpl Infect Dis 2011;13:101-8. DOI:
http://dx.doi.org/10.1111/j.1399-3062.2011.00619.x
http://dx.doi.org/10.1111/j.1399-3062.20...
25 Drachenberg CB, Papadimitriou JC, Ramos E. Histologic versus molecular
diagnosis of BK polyomavirus-associated nephropathy: a shifting paradigm? Clin J Am
Soc Nephrol 2006;1:374-9.
26 Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK
polyomavirus in solid organ transplantation. Am J Transplant 2013;13:179-88. DOI:
http://dx.doi.org/10.1111/ajt.12110
http://dx.doi.org/10.1111/ajt.12110...
27 Singh HK, Andreoni KA, Madden V, True K, Detwiler R, Weck K, et al.
Presence of urinary Haufen accurately predicts polyomavirus nephropathy. J Am Soc
Nephrol 2009;20:416-27. DOI:
http://dx.doi.org/10.1681/ASN.2008010117
http://dx.doi.org/10.1681/ASN.2008010117...
28 Westervelt JD, Alexander BD, Costa SF, Miller SE, Howell DN, Smith SR.
Detection of BK polyomavirus after kidney transplantation: a comparison of urine
electron microscopy with plasma polymerase chain reaction. Clin Transplant
2013;27:E42-8. DOI: http://dx.doi.org/10.1111/ctr.12048
http://dx.doi.org/10.1111/ctr.12048...
29 Knight RJ, Gaber LW, Patel SJ, DeVos JM, Moore LW, Gaber AO. Screening
for BK viremia reduces but does not eliminate the risk of BK nephropathy: a
single-center retrospective analysis. Transplantation 2013;95:949-54. DOI:
http://dx.doi.org/10.1097/TP.0b013e31828423cd
http://dx.doi.org/10.1097/TP.0b013e31828...
-3030 Drachenberg C, Hirsch HH, Papadimitriou JC, Mozafari P, Wali R, McKinney
JD, et al. Cost efficiency in the prospective diagnosis and follow-up of polyomavirus
allograft nephropathy. Transplant Proc 2004;36:3028-31. PMID: 15686687 DOI:
http://dx.doi.org/10.1016/j.transproceed.2004.10.045
http://dx.doi.org/10.1016/j.transproceed...
Successful clearance
or reduction of viremia is achieved in more than 80% of patients after 4 to 6
months.3434 Schaub S, Hirsch HH, Dickenmann M, Steiger J, Mihatsch MJ, Hopfer H, et
al. Reducing immunosuppression preserves allograft function in presumptive and
definitive polyomavirus-associated nephropathy. Am J Transplant 2010;10:2615-23. DOI:
http://dx.doi.org/10.1111/j.1600-6143.2010.03310.x
http://dx.doi.org/10.1111/j.1600-6143.20...
,3535 Lee BT, Gabardi S, Grafals M, Hofmann RM, Akalin E, Aljanabi A, et al.
Efficacy of levofloxacin in the treatment of BK viremia: a multicenter,
double-blinded, randomized, placebo-controlled trial. Clin J Am Soc Nephrol
2014;9:583-9. DOI: http://dx.doi.org/10.2215/CJN.04230413
http://dx.doi.org/10.2215/CJN.04230413...
Viremia should be continuously monitored every 2 to 4 weeks along
with the levels of serum creatinine after reducing immunossupression.3131 Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group.
KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J
Transplant 2009;9:S1-155.
When viremia is detected, a graft biopsy is usually indicated before reducing
immunossupression, mainly in case of renal function deterioration, to distinct BKVN from
rejection. Even if kidney function is unchanged, biopsy should be considered for those
patients at a higher immunological risk in order to exclude a sub-clinical rejection
episode.2626 Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK
polyomavirus in solid organ transplantation. Am J Transplant 2013;13:179-88. DOI:
http://dx.doi.org/10.1111/ajt.12110
http://dx.doi.org/10.1111/ajt.12110...
There is no clear evidence to support any specific modification of the immunosuppressive
therapy. However, in vitro analyses suggest that reduction or withdrawn
of calcineurin inhibitors should be the first step in immunossupression modification due
to its effects on T cells.3636 Egli A, Köhli S, Dickenmann M, Hirsch HH. Inhibition of polyomavirus
BK-specific T-Cell responses by immunosuppressive drugs. Transplantation
2009;88:1161-8. PMID: 19935369 DOI:
http://dx.doi.org/10.1097/TP.0b013e3181bca422
http://dx.doi.org/10.1097/TP.0b013e3181b...
Reduction or
withdrawn of anti-proliferative drugs, mainly mycophenolate, is also an usual target for
changing immunossupressive regimen.3434 Schaub S, Hirsch HH, Dickenmann M, Steiger J, Mihatsch MJ, Hopfer H, et
al. Reducing immunosuppression preserves allograft function in presumptive and
definitive polyomavirus-associated nephropathy. Am J Transplant 2010;10:2615-23. DOI:
http://dx.doi.org/10.1111/j.1600-6143.2010.03310.x
http://dx.doi.org/10.1111/j.1600-6143.20...
On the
other hand, in vitro analysis demonstrated a favorable action of mTOR
inhibitors on BKVN progression.3737 Wali RK, Drachenberg C, Hirsch HH, Papadimitriou J, Nahar A, Mohanlal V,
et al. BK virus-associated nephropathy in renal allograft recipients: rescue therapy
by sirolimus-based immunosuppression. Transplantation 2004;78:1069-73. PMID: 15480176
DOI: http://dx.doi.org/10.1097/01.TP.0000142127.84497.50
http://dx.doi.org/10.1097/01.TP.00001421...
Thus, despite
the lack of controlled studies, it seems reasonable, at least for patients with a lower
risk of rejection, the strategy of withdrawn or reducing tacrolimus and mycophenolate by
approximately 25% to 50%,2626 Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK
polyomavirus in solid organ transplantation. Am J Transplant 2013;13:179-88. DOI:
http://dx.doi.org/10.1111/ajt.12110
http://dx.doi.org/10.1111/ajt.12110...
meanwhile it might be
considered to introduce mTOR inhibitors to the immunossupressive regimen. After
reduction of immunossupression, renal function should be closely monitored due to the
risk of rejection.
While reducing immunosuppression is a logical first line therapy, a second line option
is not well defined. For these patients who fail to decrease viremia after reduction of
immunossupression, the use of immunoglobulin, cidofovir and fluoroquinolone has been
attempted despite unclear benefits. Among those options, the use of fluoroquinolones was
more extensively studied. In vitro analyses have shown that
fluoroquinolones could have antiviral properties by inhibiting BKV replication.3838 Sharma BN, Li R, Bernhoff E, Gutteberg TJ, Rinaldo CH. Fluoroquinolones
inhibit human polyomavirus BK (BKV) replication in primary human kidney cells.
Antiviral Res 2011;92:115-23. PMID: 21798289 DOI:
http://dx.doi.org/10.1016/j.antiviral.2011.07.012
http://dx.doi.org/10.1016/j.antiviral.20...
Retrospective studies suggested that
fluoroquinolones, used as pneumocystis prophylaxis, were effective at preventing BKPyV
viremia after HSCT and kidney transplant.3939 Leung AY, Chan MT, Yuen KY, Cheng VC, Chan KH, Wong CL, et al.
Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic
hematopoietic stem cell transplantation. Clin Infect Dis 2005;40:528-37. PMID:
15712075 DOI: http://dx.doi.org/10.1086/427291
http://dx.doi.org/10.1086/427291...
,4040 Gabardi S, Waikar SS, Martin S, Roberts K, Chen J, Borgi L, Sheashaa H,
et al. Evaluation of fluoroquinolones for the prevention of BK viremia after renal
transplantation. Clin J Am Soc Nephrol 2010;5:1298-304. DOI:
http://dx.doi.org/10.2215/CJN.08261109
http://dx.doi.org/10.2215/CJN.08261109...
However, a recent
randomized clinical trial failed to show any benefit of fluoroquinolones in kidney
transplant recipients with BKPyV viremia.3535 Lee BT, Gabardi S, Grafals M, Hofmann RM, Akalin E, Aljanabi A, et al.
Efficacy of levofloxacin in the treatment of BK viremia: a multicenter,
double-blinded, randomized, placebo-controlled trial. Clin J Am Soc Nephrol
2014;9:583-9. DOI: http://dx.doi.org/10.2215/CJN.04230413
http://dx.doi.org/10.2215/CJN.04230413...
Cidofovir is a nucleotide analogue of cytosine which acts on viral DNA and is usually
used in the treatment of CMV complications in HIV patients. Benefits of ciclofovir in
patients with BKVN were described only in small non-controlled studies.4141 Cabello V, Margarit N, Díaz Pedrero M, Bernal G, Pereira P, Gentil MA.
Treatment of BK virus-associated nephropathy with Cidofovir in renal transplantation.
Transplant Proc 2008;40:2930-2. PMID: 19010151 DOI:
http://dx.doi.org/10.1016/j.transproceed.2008.09.002
http://dx.doi.org/10.1016/j.transproceed...
,4242 Kadambi PV, Josephson MA, Williams J, Corey L, Jerome KR, Meehan SM, et
al. Treatment of refractory BK virus-associated nephropathy with cidofovir. Am J
Transplant 2003;3:186-91. DOI:
http://dx.doi.org/10.1034/j.1600-6143.2003.30202.x
http://dx.doi.org/10.1034/j.1600-6143.20...
Due to its nephrotoxicity, ciclofovir should be considered for treatment
of BKVN only when other options have failed.
Intravenous immunoglobulin administration for the treatment of BKVN is an attractive
idea since BKPyV is ubiquitous in human population. Thus, it is expected that
immunoglobulin contains antibodies against this virus. The use of immunoglobulin seems
especially attracting when the diagnosis of allograft rejection cannot be ruled out. In
this case, the use of massive dose of immunoglobulin could be useful for both rejection
and BKVN. However, there is a paucity of studies addressing the use of immunoglobulin in
the treatment BKVN4343 Sener A, House AA, Jevnikar AM, Boudville N, McAlister VC, Muirhead N,
et al. Intravenous immunoglobulin as a treatment for BK virus associated nephropathy:
one-year follow-up of renal allograft recipients. Transplantation 2006;81:117-20.
PMID: 16421486 DOI:
http://dx.doi.org/10.1097/01.tp.0000181096.14257.c2
http://dx.doi.org/10.1097/01.tp.00001810...
44 Sharma AP, Moussa M, Casier S, Rehman F, Filler G, Grimmer J.
Intravenous immunoglobulin as rescue therapy for BK virus nephropathy. Pediatr
Transplant 2009;13:123-9. DOI:
http://dx.doi.org/10.1111/j.1399-3046.2008.00958.x
http://dx.doi.org/10.1111/j.1399-3046.20...
-4545 Anyaegbu EI, Almond PS, Milligan T, Allen WR, Gharaybeh S, Al-Akash SI.
Intravenous immunoglobulin therapy in the treatment of BK viremia and nephropathy in
pediatric renal transplant recipients. Pediatr Transplant 2012;16:E19-24. DOI:
http://dx.doi.org/10.1111/j.1399-3046.2010.01384.x
http://dx.doi.org/10.1111/j.1399-3046.20...
and randomized clinical trials are needed.
Repeat transplantation is a feasible option after graft loss due to BKVN. A study of 126
patients who underwent repeat kidney transplantation after graft loss due to BKVN showed
a 3-year graft survival rate of 93.6%.4646 Dharnidharka VR, Cherikh WS, Neff R, Cheng Y, Abbott KC.
Retransplantation after BK virus nephropathy in prior kidney transplant: an OPTN
database analysis. Am J Transplant 2010;10:1312-5. DOI:
http://dx.doi.org/10.1111/j.1600-6143.2010.03083.x
http://dx.doi.org/10.1111/j.1600-6143.20...
In
another study, 11 out of 31 patients presented post-transplant BKPyV viremia but with
only two of them experiencing BKVN. Viremia clearance after BKVN in the initial
transplant was significantly associated with a lower risk of recurrence after repeat
transplantation.4747 Geetha D, Sozio SM, Ghanta M, Josephson M, Shapiro R, Dadhania D, et al.
Results of repeat renal transplantation after graft loss from BK virus nephropathy.
Transplantation 2011;92:781-6. PMID: 21836535 DOI:
http://dx.doi.org/10.1097/TP.0b013e31822d08c1
http://dx.doi.org/10.1097/TP.0b013e31822...
The post-transplant
management should follow the screening and follow-up previously described but always
having in mind the narrow limits between excessive immunossupression, with risk of
reactivation of BKPyV viremia, and a loose immunossupressive regimen for a patient
already sensitized by the previous transplant.
Conclusions
The advent of newer, more potent immunosuppressive agents may contribute to an apparently increasing incidence of BKVN in kidney transplant recipients. The optimal screening method and timing to detect BKPyV remains to be determined and cutoff values, especially for quantitative tests, need to be defined and standardized. Currently, early diagnosis and reduction of immunosupression therapy seems to be the most efficacious treatment for BKPyV infection.
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FAPERJ (Processo: E-26/111.225/2013).
Publication Dates
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Publication in this collection
Oct-Dec 2014
History
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Received
13 Feb 2014 -
Accepted
22 May 2014