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Biomedicines Jul 2023Infectious agents can pose a significant challenge in kidney transplantation, as they have the potential to cause direct infections in the transplanted kidney. These... (Review)
Review
Infectious agents can pose a significant challenge in kidney transplantation, as they have the potential to cause direct infections in the transplanted kidney. These infections can lead to a decline in kidney function and reduce the longevity of the transplanted kidney. Common post-transplant allograft infections include bacterial pyelonephritis and the BK virus infection, while adenovirus, JC virus, and cytomegalovirus are less frequent but can also lead to significant allograft dysfunctions. The histopathological features of these infections are characterized by the infiltration of inflammatory cells in the kidney interstitial area and the presence of viral nuclear inclusions or cytopathic changes in the renal tubular epithelial cells. The confirmation of causative organisms can be achieved by immunohistochemical staining or the visualization of viral particles using electron microscopic examination. However, these methods typically require a longer turnaround time and are not readily available in developing countries, unlike standard hematoxylin-eosin staining. Notably, the differential diagnosis of interstitial inflammation in kidney allografts almost always includes T cell-mediated rejection, which has a different treatment approach than allograft infections. The aim of this review was to prompt clinicians to identify diverse pathological alterations as observed in kidney allograft biopsies, thereby facilitating further investigations and the management of suspected kidney allograft infections.
PubMed: 37509541
DOI: 10.3390/biomedicines11071902 -
Reviews in Medical Virology Jul 2020BK polyomavirus (BKPyV or BKV) is a non-enveloped, circular double-stranded DNA virus that may exceed 80% seroprevalence in adults. BKV infection typically occurs during... (Review)
Review
BK polyomavirus (BKPyV or BKV) is a non-enveloped, circular double-stranded DNA virus that may exceed 80% seroprevalence in adults. BKV infection typically occurs during childhood, and the majority of adults are latently infected. While BKV infection is rarely associated with clinical disease in most individuals, in immunosuppressed individuals, reactivation may cause kidney (BK-associated nephropathy) or bladder (hemorrhagic cystitis and ureteral stenosis) injury. No antiviral therapies have been approved for the treatment of BKV infection. Reducing immunosuppression is the most effective therapy, although this is not feasible in many patients. Thus, a robust understanding of viral pathogenesis and viral diversity remains important for the development of future therapeutic strategies. Studies of BKV diversity are quite sparse compared to other common viral infections; thus, much of our understanding of BVK variability and evolution relies heavily analogous studies of other viruses such as HIV or viral hepatitis. We provide a comprehensive review of BKV diversity at the population and individual level with careful consideration of how viral variability may impact viral replication, pathogenesis, tropism, and protein function. We also discuss a number of outstanding questions related to BK virus diversity that should be explored rigorously in future studies.
Topics: Animals; BK Virus; Biodiversity; Evolution, Molecular; Genetic Variation; Genome, Viral; Genomics; Humans; Phylogeny; Polyomavirus Infections
PubMed: 32128960
DOI: 10.1002/rmv.2102 -
Clinical Journal of the American... Dec 2018
Topics: Algorithms; BK Virus; Female; Humans; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Postoperative Complications; Tumor Virus Infections
PubMed: 30242026
DOI: 10.2215/CJN.04080318 -
Viruses Jul 2021The BK polyomavirus (BKPyV), a representative of the family Polyomaviridae, is widespread in the human population. While the virus does not cause significant clinical... (Review)
Review
The BK polyomavirus (BKPyV), a representative of the family Polyomaviridae, is widespread in the human population. While the virus does not cause significant clinical symptoms in immunocompetent individuals, it is activated in cases of immune deficiency, both pharmacological and pathological. Infection with the BKPyV is of particular importance in recipients of kidney transplants or HSC transplantation, in which it can lead to the loss of the transplanted kidney or to haemorrhagic cystitis, respectively. Four main genotypes of the virus are distinguished on the basis of molecular differentiation. The most common genotype worldwide is genotype I, with a frequency of about 80%, followed by genotype IV (about 15%), while genotypes II and III are isolated only sporadically. The distribution of the molecular variants of the virus is associated with the region of origin. BKPyV subtype Ia is most common in Africa, Ib-1 in Southeast Asia, and Ib-2 in Europe, while Ic is the most common variant in Northeast Asia. The development of molecular methods has enabled significant improvement not only in BKPyV diagnostics, but in monitoring the effectiveness of treatment as well. Amplification of viral DNA from urine by PCR (Polymerase Chain Reaction) and qPCR Quantitative Polymerase Chain Reaction) is a non-invasive method that can be used to confirm the presence of the genetic material of the virus and to determine the viral load. Sequencing techniques together with bioinformatics tools and databases can be used to determine variants of the virus, analyse their circulation in populations, identify relationships between them, and investigate the directions of evolution of the virus.
Topics: Animals; BK Virus; DNA, Viral; Genetic Variation; Genome, Viral; Genomics; Genotype; Immunocompromised Host; Kidney; Kidney Transplantation; Mice; Oncogenic Viruses; Pathology, Molecular; Polyomavirus Infections; Transplant Recipients; Tumor Virus Infections; Viral Load
PubMed: 34452367
DOI: 10.3390/v13081502 -
Virus Research Mar 2017The etiological role of human papillomavirus (HPV) in anogenital tract and head and neck cancers is well established. However, only a low percentage of HPV-positive... (Review)
Review
The etiological role of human papillomavirus (HPV) in anogenital tract and head and neck cancers is well established. However, only a low percentage of HPV-positive women develop cancer, indicating that HPV is necessary but not sufficient in carcinogenesis. Several biological and environmental cofactors have been implicated in the development of HPV-associated carcinoma that include immune status, hormonal changes, parity, dietary habits, tobacco usage, and co-infection with other sexually transmissible agents. Such cofactors likely contribute to HPV persistent infection through diverse mechanisms related to immune control, efficiency of HPV infection, and influences on tumor initiation and progression. Conversely, HPV co-infection with other factors may also harbor anti-tumor effects. Here, we review epidemiological and experimental studies investigating human immunodeficiency virus (HIV), herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), BK virus (BKV), JC virus (JCV), and adeno-associated virus (AAV) as viral cofactors in or therapeutic factors against the development of genital and oral HPV-associated carcinomas.
Topics: Anus Neoplasms; BK Virus; Carcinogenesis; Coinfection; Cytomegalovirus; Dependovirus; Female; Genital Neoplasms, Female; HIV; Head and Neck Neoplasms; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 4, Human; Humans; JC Virus; Papillomaviridae; Papillomavirus Infections; Protective Factors; Risk Factors
PubMed: 27826043
DOI: 10.1016/j.virusres.2016.11.002 -
The Journal of Infectious Diseases May 2023Urine exosomal bkv-miR-B1-5p is associated with BK virus (BKV) nephropathy (BKVN); however, its posttransplantation changes and predictability for BKVN have not been... (Clinical Trial)
Clinical Trial
BACKGROUND
Urine exosomal bkv-miR-B1-5p is associated with BK virus (BKV) nephropathy (BKVN); however, its posttransplantation changes and predictability for BKVN have not been determined in kidney transplant recipients (KTRs).
METHODS
Urine exosomal bkv-miR-B1-5p and urine and plasma BKV DNA were measured at 2 weeks and 3, 6, and 12 months posttransplant in 83 KTRs stratified into biopsy-proven or presumptive BKVN, BKV viruria, and no evidence of BKV reactivation. Joint model, multivariable Cox model and receiver operating characteristic curve (ROC) were used to investigate the association of each assay with the following events: a composite of biopsy-proven or presumptive BKVN, and biopsy-proven BKVN.
RESULTS
Urine exosomal bkv-miR-B1-5p and urine and plasma BKV DNA showed similar posttransplant time-course changes. Joint models incorporating serial values demonstrated significant associations of all assays with the events, and Cox analyses using single time point values at 2 weeks posttransplant showed that only urine exosomal bkv-miR-B1-5p was significantly associated with the events, although it did not outperform urine BKV DNA in ROC analyses.
CONCLUSIONS
Urine exosomal bkv-miR-B1-5p was associated with BKVN as were urine and plasma BKV DNA loads on serial follow-up, and might have potential as a predictive marker for BKVN during the early posttransplant period.
CLINICAL TRIALS REGISTRATION
Clinical Research Information Service (https://cris.nih.go.kr/cris/), KCT0001010.
Topics: Humans; BK Virus; DNA, Viral; Kidney Diseases; Kidney Transplantation; MicroRNAs; Polyomavirus Infections; Transplant Recipients; Tumor Virus Infections
PubMed: 36374933
DOI: 10.1093/infdis/jiac440 -
The New Microbiologica May 2023BK virus (BKV) associated with hemorrhagic cystitis (HC) is the most important complication that develops after hematopoietic stem cell transplantation (HSCT) in...
BK virus (BKV) associated with hemorrhagic cystitis (HC) is the most important complication that develops after hematopoietic stem cell transplantation (HSCT) in patients with hematological malignancies. This study aims to investigate BKV infections and HC in pediatric patients after allogeneic hematopoietic stem cell transplantation. Between November 2018 and November 2019, a total of 51 patients between the ages of 11 months and 17 years were included in the study. BKV Bosphore ® v1 quantification kit (Geneworks Anatolia, Turkey) was used for the detection of BKV DNA in urine and blood samples. Among the total of 51 patients, the incidence of BKV infection was found to be 86.3%. Allogeneic HSCT was performed in 40 patients and autologous HSCT in 11 patients. BK viruria and/or viremia were detected in 85% (44) of patients who underwent allogeneic HSCT and in 90% in the autologous group. High-level BK viruria (>107 copies/mL) was found in 41% (9) of 22 patients who were BKV positive before transplantation, while in 27.5% (8) of 29 patients who were BKV negative before transplantation; thus, BKV positivity before transplantation was considered a risk factor for high-level BK viruria. Acute GVHD developed in 6 of 40 patients in the allogeneic group. HC was prevented in 12 (67%) of 18 patients who received preemptive treatment, while HC developed in 6 (33%). HC occurred at a median of 35 days (17-49 days) post-transplant. Despite preemptive treatment, 6 (15%) patients who developed HC associated with BKV were in the allogeneic group but not in the autologous group. Of these patients with HC, 5 received a myeloablative treatment regimen, and 1 patient was given a reduced-intensity treatment regimen. The viral load in urine was found to be 107-9 copies/mL within 2 weeks before the development of HC and has been identified as a prognostic indicator. In conclusion, early diagnosis of viral infections by monitoring BKV viral load in HSCT patients will be effective in preventing the progression of complications such as BKV-associated HC by providing timely initiation of preemptive treatment.
Topics: Humans; Child; Infant; Cystitis; Risk Factors; Hematopoietic Stem Cell Transplantation; Polyomavirus Infections; Transplant Recipients; BK Virus; Hemorrhage
PubMed: 37247234
DOI: No ID Found -
Indian Journal of Nephrology 2018BK polyomavirus (BKV) is a challenging problem for the transplant nephrologist. Various strategies have been used to prevent or treat BK virus nephropathy (BKVN). These... (Review)
Review
BK polyomavirus (BKV) is a challenging problem for the transplant nephrologist. Various strategies have been used to prevent or treat BK virus nephropathy (BKVN). These include reduction in immunosuppression, intravenous immune globulin, cidofovir, leflunomide, and the fluoroquinolone antibiotics. All these agents have their own toxicities. Great interest was shown to use fluoroquinolones to prevent BKVN after its useful experience was reported in bone marrow transplant. Fluoroquinolones being cheap and easily available, attracted nephrologists to use it, for prevention of BKVN. These agents have been shown studies to be effective. However, there are mixed results about their effectiveness in prevention of BKVN in clinical setting. This review will focus the evidence available for using fluoroquinolones in prevention of BKVN and its usefulness. Furthermore, a way forward to use these agents or not for prevention of BKVN will also be discussed.
PubMed: 30158742
DOI: 10.4103/ijn.IJN_251_17 -
World Journal of Transplantation Dec 2017BK virus (BKV) is a polyomavirus that is able to cause renal dysfunction in transplanted grafts BK virus-associated nephritis (BKVAN). This condition was mis-diagnosed... (Review)
Review
BK virus (BKV) is a polyomavirus that is able to cause renal dysfunction in transplanted grafts BK virus-associated nephritis (BKVAN). This condition was mis-diagnosed in the past due to clinical and histopthological similarities with acute rejection. Due to the prevalence of the virus in the population, it is an important pathogen in this context, and so it is important to understand how this virus functions and its' relationship with the pathogenesis of BKVN. Screening for BKV often reveals viruria and/or viremia, which then manifests as BKVN, which can be asymptomatic or result in clinical features namely renal dysfunction. The pathogenesis of BKV infection is still unclear and needs to be further investigated; nevertheless there are a variety of hypotheses that indicate that there are a host of factors that play important roles. Treatments for BKVAN include a reduction in immunosuppression, the use of antiviral therapy or the combination of both treatment options.
PubMed: 29312862
DOI: 10.5500/wjt.v7.i6.329 -
Pediatric Nephrology (Berlin, Germany) Apr 2021After pediatric kidney transplantation, immunosuppressive therapy causes an increased risk of severe viral complications, especially from cytomegalovirus (CMV), BK... (Review)
Review
After pediatric kidney transplantation, immunosuppressive therapy causes an increased risk of severe viral complications, especially from cytomegalovirus (CMV), BK polyomavirus (BKPyV) or Epstein-Barr virus (EBV), and less frequent from adenovirus (ADV). However, suitable predictive markers for the individual outcome of viral infections are missing and the therapeutic management remains a challenge to the success of pediatric kidney transplantation. Virus-specific T cells are known for controlling viral replication and there is growing evidence that virus-specific T cells may serve as a prognostic marker to identify patients at risk for viral complications. This review provides an overview of the usability of virus-specific T cells for improving diagnostic and therapeutic management of viral infections with reference to the necessity of antiviral prophylaxis, timing of pre-emptive therapy, and dosing of immunosuppressive medication after pediatric kidney transplantation. Several studies demonstrated that high levels of virus-specific T cells are associated with decrease of virus load and favorable outcome, whereas lack of virus-specific T cells coincided with virus-induced complications. Accordingly, the additional monitoring of virus-specific T cells aims to personalize the management of antiviral therapy, identify overimmunosuppression, and avoid unnecessary therapeutic interventions. Prospective randomized trials in pediatric kidney recipients comparing standard antiviral and immunosuppressive regimens with T cell-guided therapeutic interventions are needed, before monitoring of virus-specific T cells is implemented in the routine care of pediatric kidney graft recipients.
Topics: Antiviral Agents; BK Virus; Child; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Kidney Transplantation; Polyomavirus Infections; Prospective Studies; T-Lymphocytes
PubMed: 32221706
DOI: 10.1007/s00467-020-04522-6