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Viruses Jul 2022BK virus maintains a latent infection that is ubiquitous in humans. It has a propensity for reactivation in the setting of a dysfunctional cellular immune response and... (Review)
Review
BK virus maintains a latent infection that is ubiquitous in humans. It has a propensity for reactivation in the setting of a dysfunctional cellular immune response and is frequently encountered in kidney transplant recipients. Screening for the virus has been effective in preventing progression to nephropathy and graft loss. However, it can be a diagnostic and therapeutic challenge. In this in-depth state-of-the-art review, we will discuss the history of the virus, virology, epidemiology, cellular response, pathogenesis, methods of screening and diagnosis, evidence-based treatment strategies, and upcoming therapeutics, along with the issue of re-transplantation in patients.
Topics: BK Virus; Humans; Kidney Transplantation; Polyomavirus Infections; Tumor Virus Infections; Viremia
PubMed: 35893681
DOI: 10.3390/v14081616 -
Genes Jul 2022Poliomavirus BK virus (BKV) is highly infective, causing asymptomatic infections during childhood. After the initial infection, a stable state of latent infection is... (Review)
Review
Poliomavirus BK virus (BKV) is highly infective, causing asymptomatic infections during childhood. After the initial infection, a stable state of latent infection is recognized in kidney tubular cells and the uroepithelium with negligible clinical consequences. BKV is an important risk factor for BKV-associated diseases, and, in particular, for BKV-associated nephropathy (BKVN) in renal transplanted recipients (RTRs). BKVN affects up to 10% of renal transplanted recipients, and results in graft loss in up to 50% of those affected. Unfortunately, treatments for BK virus infection are restricted, and there is no efficient prophylaxis. In addition, consequent immunosuppressive therapy reduction contributes to immune rejection. Increasing surveillance and early diagnosis based upon easy and rapid analyses are resulting in more beneficial outcomes. In this report, the current status and perspectives in the diagnosis and treatment of BKV in RTRs are reviewed.
Topics: BK Virus; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Tumor Virus Infections
PubMed: 35886073
DOI: 10.3390/genes13071290 -
Experimental and Clinical... Nov 2020The BK polyomavirus was isolated in 1971; it has been a significant risk factor for both graft dysfunction and failure in renal transplant recipients. So far, no... (Review)
Review
The BK polyomavirus was isolated in 1971; it has been a significant risk factor for both graft dysfunction and failure in renal transplant recipients. So far, no specific treatment option has been available for effective treatment or prophylaxis for BK virus infections. Although the use of heavy immunosuppression has been the main risk factor for BK virus infection, other risk factors are equally important, including elderly recipients, prior rejection episodes, male sex, human leukocyte antigen mismatching, prolonged cold ischemia time, pretransplant BK virus serostatus, and ureteral stenting. Regular follow-up for BK virus infections according to each institution's policy has been, so far, effective in detecting patients with BK virus viremia and consequently preventing allograft loss. The mainstay of management continues to be reduction of immunosuppression. However, newer options are providing new insights, such as cellular immunotherapy. In this review, we will address the diagnosis, screening, new diagnostic tools, and updated management of BK virus infections.
Topics: Adoptive Transfer; Antiviral Agents; BK Virus; Drug Substitution; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy; Kidney Transplantation; Opportunistic Infections; Polyomavirus Infections; Risk Assessment; Risk Factors; Treatment Outcome; Tumor Virus Infections
PubMed: 32552624
DOI: 10.6002/ect.2019.0254 -
Clinical Transplantation Sep 2019The present AST-IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely...
The present AST-IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely non-kidney solid organ transplantation (SOT). As pretransplant risk factors in KT donors and recipients presently do not translate into clinically validated measures regarding organ allocation, antiviral prophylaxis, or screening, all KT recipients should be screened for BKPyV-DNAemia monthly until month 9, and then every 3 months until 2 years posttransplant. Extended screening after 2 years may be considered in pediatric KT. Stepwise immunosuppression reduction is recommended for KT patients with plasma BKPyV-DNAemia of >1000 copies/mL sustained for 3 weeks or increasing to >10 000 copies/mL reflecting probable and presumptive BKPyV-associated nephropathy, respectively. Reducing immunosuppression is also the primary intervention for biopsy-proven BKPyV-associated nephropathy. Hence, allograft biopsy is not required for treating BKPyV-DNAemic patients with baseline renal function. Despite virological rationales, proper randomized clinical trials are lacking to generally recommend treatment by switching from tacrolimus to cyclosporine-A, from mycophenolate to mTOR inhibitors or leflunomide or by the adjunct use of intravenous immunoglobulins, leflunomide, or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. Retransplantation after allograft loss due to BKPyV nephropathy can be successful if BKPyV-DNAemia is definitively cleared, independent of failed allograft nephrectomy.
Topics: Antiviral Agents; BK Virus; Humans; Organ Transplantation; Polyomavirus Infections; Practice Guidelines as Topic; Societies, Medical; Transplant Recipients; Tumor Virus Infections
PubMed: 30859620
DOI: 10.1111/ctr.13528 -
The Journal of Antimicrobial... Jan 2018To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT. (Review)
Review
OBJECTIVES
To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT.
METHODS
Review of English literature and evidence-based recommendations by expert consensus.
RESULTS
BKPyV-HC occurs in 8%-25% of paediatric and 7%-54% of adult recipients undergoing allogeneic HSCT. Diagnosis requires the triad of cystitis, macro-haematuria and high urine BKPyV loads >7 log10 copies/mL, and exclusion of other relevant aetiologies. BKPyV viraemia is frequent and may serve as a more specific semiquantitative follow-up marker. No randomized controlled trials are available to inform antiviral prophylaxis or treatment. However, hyper-hydration and/or bladder irrigation showed limited prophylactic value. Fluoroquinolones are not effective for prophylaxis or treatment, but rather increase antibiotic resistance. Hyperbaric oxygen or fibrin glue is marginally effective based on small case series from correspondingly equipped centres. Although cidofovir has been reported to improve and/or reduce BKPyV viraemia or viruria, the current data do not support its regular use.
CONCLUSIONS
BKPyV-HC remains a disabling unmet clinical need in HSCT that requires novel approaches supported by proper clinical trials.
Topics: BK Virus; Cystitis; Drug Resistance, Viral; Hematopoietic Stem Cell Transplantation; Humans; Polyomavirus Infections; Risk Factors; Tumor Virus Infections; Urinary Bladder
PubMed: 29190347
DOI: 10.1093/jac/dkx324 -
American Journal of Transplantation :... Aug 2017
Topics: BK Virus; Humans; Kidney Diseases; Polyomavirus Infections
PubMed: 28510315
DOI: 10.1111/ajt.14358 -
Nephrology, Dialysis, Transplantation :... Mar 2021BK virus is a polyomavirus with seroprevalence rates of 80% in adults. Infection is usually acquired during childhood, and the virus is benign or pathologic depending on... (Review)
Review
BK virus is a polyomavirus with seroprevalence rates of 80% in adults. Infection is usually acquired during childhood, and the virus is benign or pathologic depending on immune status. The virus reactivates in immunodeficiency states, mostly among transplant (either kidney or bone marrow) recipients. There are approximately 15 000 renal transplants every year in the USA, of which 5-10% develop BK polyomavirus nephropathy; 50-80% of patients who develop nephropathy go on to develop graft failure. BK virus is associated with BK polyomavirus nephropathy, ureteral stenosis, late-onset hemorrhagic cystitis, bladder cancer and other nonlytic large T-expressing carcinomas. The renal spectrum begins with viruria and can end with graft failure. The clinical spectrum and outcomes vary among transplant patients. New noninvasive diagnostic methods, such as urinary polyomavirus Haufen detected by electron microscopy, are currently under study. Treatment is primarily directed at decreasing immunosuppression but may be associated with graft rejection. Repeat transplantation is encouraged as long as viral clearance in plasma prior to transplant is accomplished. There remain no definitive data regarding the utility of transplant nephrectomy.
Topics: BK Virus; Graft Rejection; Humans; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Tumor Virus Infections
PubMed: 31891401
DOI: 10.1093/ndt/gfz273 -
Viral Immunology Mar 2016Recent information demonstrated that BK virus reactivation is a dominant complication after kidney transplantation, which occurs because of immunosuppression. BK virus... (Review)
Review
Recent information demonstrated that BK virus reactivation is a dominant complication after kidney transplantation, which occurs because of immunosuppression. BK virus reactivation is the main reason of transplanted kidney losing. Immune response against BK virus is the major inhibitor of the virus reactivation. Therefore, improving our knowledge regarding the main parameters that fight against BK viruses can shed light on to direct new treatment strategies to suppress BK infection. Innate immunity consists of numerous cell systems and also soluble molecules, which not only suppress virus replication, but also activate adaptive immunity to eradicate the infection. Additionally, it appears that immune responses against reactivated BK virus are the main reasons for induction of BK virus-associated nephropathy (BKAN). Thus, improving our knowledge regarding the parameters and detailed mechanisms of innate immunity and also the status of innate immunity of the patients with BK virus reactivation and its complications can introduce new prospective strategies to either prevent or as therapy of the complication. Therefore, this review was aimed to collate the most recent data regarding the roles played by innate immunity against BK virus and also the status of innate immunity in the patients with reactivation BK virus and BKAN.
Topics: BK Virus; Host-Pathogen Interactions; Humans; Immunity, Innate; Polyomavirus Infections; Virus Activation; Virus Latency
PubMed: 26752693
DOI: 10.1089/vim.2015.0099 -
Scientific Reports Jan 2021BK virus associated nephropathy (BKN) is an important cause of kidney allograft failure. In a cohort of paediatric kidney transplant recipients, we aimed to understand...
BK virus associated nephropathy (BKN) is an important cause of kidney allograft failure. In a cohort of paediatric kidney transplant recipients, we aimed to understand the incidence and clinical outcome associated with BKN, as well as identify risk factors for BKN and BK viraemia development. We retrospectively analysed all patients who received a kidney transplant and received follow up care in our centre between 2009-2019. Among 106 patients included in the study (mean follow up 4.5 years), 32/106 (30.2%) patients experienced BK viraemia. The incidence of BKN was 7/106 (6.6%). The median time of BK viraemia development post-transplant was 279.5 days compared to 90.0 days for BKN. Development of BKN was associated with younger age at transplantation (p = 0.013). Development of BK viraemia was associated with negative recipient serology for cytomegalovirus (CMV) at time of transplantation (p = 0.012) and a higher net level of immunosuppression (p = 0.039). There was no difference in graft function at latest follow up between those who experienced BKN and those without BKN. This study demonstrates that BK virus infection is associated with younger age at transplantation, CMV negative recipient serostatus and higher levels of immunosuppression. Judicious monitoring of BK viraemia in paediatric transplant recipients, coupled with timely clinical intervention can result in similar long-term outcomes for BKN patients compared to controls.
Topics: Aftercare; Age Factors; BK Virus; Child; Female; Graft Rejection; Humans; Incidence; Kidney Diseases; Kidney Transplantation; Male; Polyomavirus Infections; Retrospective Studies; Viremia
PubMed: 33510329
DOI: 10.1038/s41598-021-82160-0 -
Viruses Nov 2017The BK virus (BKPyV) is a member of the family first isolated in 1971. BKPyV causes frequent infections during childhood and establishes persistent infections with... (Review)
Review
The BK virus (BKPyV) is a member of the family first isolated in 1971. BKPyV causes frequent infections during childhood and establishes persistent infections with minimal clinical implications within renal tubular cells and the urothelium. However, reactivation of BKPyV in immunocompromised individuals may cause serious complications. In particular, with the implementation of more potent immunosuppressive drugs in the last decade, BKPyV has become an emerging pathogen in kidney and bone marrow transplant recipients where it often causes associated nephropathy and haemorrhagic cystitis, respectively. Unfortunately, no specific antiviral against BKPyV has been approved yet and the only therapeutic option is a modulation of the immunosuppressive drug regimen to improve immune control though it may increase the risk of rejection. A better understanding of the BKPyV life cycle is thus needed to develop efficient treatment against this virus. In this review, we provide an update on recent advances in understanding the biology of BKPyV.
Topics: Antiviral Agents; BK Virus; Humans; Immunocompromised Host; Immunosuppressive Agents; Polyomavirus Infections; Transplant Recipients; Virus Activation
PubMed: 29099746
DOI: 10.3390/v9110327