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Biomedicines May 2024BK polyomavirus (BKPyV) is still a real threat in the management of kidney transplantation. Immunosuppressive treatment disrupts the equilibrium between virus... (Review)
Review
BK polyomavirus (BKPyV) is still a real threat in the management of kidney transplantation. Immunosuppressive treatment disrupts the equilibrium between virus replication and immune response, and uncontrolled BKPyV replication leads to nephropathy (BKPyV nephropathy). The first evidence of BKPyV reactivation in transplant recipients is the detection of viral shedding in urine, which appears in 20% to 60% of patients, followed by BKPyV viremia in 10-20% of kidney transplant recipients. BKPyV nephropathy eventually occurs in 1-10% of this population, mainly within the first 2 years post-transplantation, causing graft loss in about half of those patients. Few data exist regarding the pediatric population and we focus on them. In this paper, we review the existing diagnostic methods and summarize the evidence on the role of BKPyV humoral and cellular immunity in modulating the clinical course of BKPyV infection and as potential predictors of the outcome. We look at the known risk factors for BKPyV nephropathy in the immunosuppressed patient. Finally, we propose a sensible clinical attitude in order to screen and manage BKPyV infection in kidney transplant children.
PubMed: 38791055
DOI: 10.3390/biomedicines12051093 -
The Journal of Histochemistry and... May 2020BK polyomavirus-associated nephropathy (BKpyVAN) remains a cause of graft loss in kidney transplant recipients on immunosuppressive therapy. Its diagnosis relies on the...
BK polyomavirus-associated nephropathy (BKpyVAN) remains a cause of graft loss in kidney transplant recipients on immunosuppressive therapy. Its diagnosis relies on the identification of BK virus (BKV) in the renal allograft biopsy by positive immunohistochemical (IHC) stain for the viral SV40 large T antigen, although in situ hybridization (ISH) for viral DNA is used in some centers. We examined tissue detection of BKV RNA by RNAscope, a novel, automated ISH test, in 61 allograft biopsies from 56 patients with BKpyVAN. We found good correlation between the estimate of BKV tissue load by RNAscope ISH and SV40 IHC ( = 0.65, 0.0001). RNAscope ISH showed 88% sensitivity and 79% specificity and, as an alternative test, could confirm the presence of BKV tissue in presumed BKpyVAN and rule out BKV as the causative agent in JC virus nephropathy. We also used tissue BK viral load estimates by both RNAscope ISH and SV40 IHC to examine the relation between tissue and plasma BK levels and found significant correlation only between BK viremia and tissue BK measured by RNAscope ISH. Our findings suggest that the RNAscope ISH assay could be a reliable test for BKV detection in allograft biopsies.
Topics: BK Virus; Biopsy; Cohort Studies; DNA, Viral; Female; Humans; Kidney; Kidney Transplantation; Male; Middle Aged; Transplantation, Homologous
PubMed: 32352851
DOI: 10.1369/0022155420922604 -
Experimental and Clinical... Sep 2023This study aimed to determine the predictive factors of BK virus viremia/nephropathy in kidney transplant recipients and to evaluate the effects of low-dose tacrolimus...
OBJECTIVES
This study aimed to determine the predictive factors of BK virus viremia/nephropathy in kidney transplant recipients and to evaluate the effects of low-dose tacrolimus plus everolimus.
MATERIALS AND METHODS
This study included 3654 kidney transplant recipients. The patients were divided into 2 groups: group 1 were BK virus negative (n = 3525, 96.5%) and group 2 were BK virus positive (n = 129, viremia 3.5%, nephropathy 1%). Predictive factors were determined by receiver operating characteristic curve analysis and logistic regression models.We also divided and analyzed patients with BK virus viremia/nephropathy into 2 groups according to immunosuppressive changes. Group 2a had been switched to low-dose tacrolimus plus everolimus (n = 54, 41.9%), and group 2b had been switched to other immunosuppressive protocols (n = 75, 58.1%).
RESULTS
We found that use of anti-T-cell lymphocyte globulin and tacrolimus, deceased donor transplant, and rejection were predictive factors for BK virus viremia/nephropathy. In addition, patients who had low-dose calcineurin inhibitor plus mammalian target of rapamycin inhibitor regimens showed a low rate of BK virus development(only 6.2% of all cases). In Group 2a, both the BK polyomavirus-associated nephropathy rate (n = 23 [42.6%] vs n = 12 [16%] in group 2b; P = .001) and viral load (DNA > 104 copies/mL) (n = 49 [90.7%] vs n = 27 [36%] in group 2b; P = .001) were increased versus group 2b. Graft function, graft survival, viral clearance, and rejection rate were similar between the groups after protocol change.
CONCLUSIONS
BK virus viremia/nephropathy rate was lower in patients who received low-dose calcineurin inhibitor plus mammalian target of rapamycin inhibitor protocols; the low-dose tacrolimus plus everolimus switch protocol after BK virus was more effective and safe than other protocols.
Topics: Humans; Tacrolimus; Everolimus; BK Virus; Kidney Transplantation; Calcineurin Inhibitors; Viremia; Immunosuppressive Agents; Sirolimus; Nephritis, Interstitial; Polyomavirus Infections; Tumor Virus Infections; Transplant Recipients; TOR Serine-Threonine Kinases
PubMed: 37885288
DOI: 10.6002/ect.2023.0065 -
Reviews in Medical Virology Jul 2019BK polyomavirus (BKV) is an important cause of graft loss in renal transplant recipients that continues to pose a significant challenge to clinicians due to its... (Review)
Review
BK polyomavirus (BKV) is an important cause of graft loss in renal transplant recipients that continues to pose a significant challenge to clinicians due to its frequently unpredictable onset, persistence, and the lack of effective antiviral agents or prevention strategies. This review covers our current understanding of epidemiology, viral transmission and disease progression, and treatment and prevention strategies that have been used to manage this disease.
Topics: BK Virus; Disease Progression; Disease Transmission, Infectious; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Polyomavirus Infections
PubMed: 30958614
DOI: 10.1002/rmv.2044 -
Acta Medica (Hradec Kralove) 2022All renal transplant recipients should undergo a regular screening for BK viral (BKV) viremia. Gradual reduction of immunosuppression is recommended in patients with...
All renal transplant recipients should undergo a regular screening for BK viral (BKV) viremia. Gradual reduction of immunosuppression is recommended in patients with persistent plasma BKV viremia for 3 weeks after the first detection, reflecting the presence of probable or suspected BKV-associated nephropathy. Reduction of immunosuppression is also a primary intervention in biopsy proven nephropathy associated with BKV (BKVN). Thus, allograft biopsy is not required to treat patients with BKV viremia with stabilized graft function. There is a lack of proper randomised clinical trials recommending treatment in the form of switching from tacrolimus to cyclosporin-A, from mycophenolate to mTOR inhibitors or leflunomide, or the additive use of intravenous immunoglobulins, leflunomide or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. There are on-going studies to evaluate the possibility of using a multi-epitope anti-BKV vaccine, administration of BKV-specific T cell immunotherapy, BKV-specific human monoclonal antibody and RNA antisense oligonucleotides. Retransplantation after allograft loss due to BKVN can be successful if BKV viremia is definitively removed, regardless of allograft nephrectomy.
Topics: Humans; Kidney Transplantation; Leflunomide; BK Virus; Viremia; Kidney Diseases; Immunosuppressive Agents; Polyomavirus Infections
PubMed: 36942701
DOI: 10.14712/18059694.2023.1 -
Kidney360 May 2021Cytomegalovirus (CMV) and BK virus (BKV) are common viral infections after kidney transplant. Their negative effects on patient and graft outcomes have been well... (Review)
Review
Cytomegalovirus (CMV) and BK virus (BKV) are common viral infections after kidney transplant. Their negative effects on patient and graft outcomes have been well described. However, despite improvement in screening and prophylaxis strategies, CMV and BKV continue to negatively affect both short- and long-term graft survival. Adequate cell-mediated immunity is essential for the control and prevention of opportunistic viral infections, such as CMV and BKV. Therefore, immune reconstitution, in particular T cell recovery, is a key factor in antiviral control after kidney transplantation. Cell-based immunotherapy offers an attractive alternative approach to traditional interventions. Adoptive T cell transfer, infusions of allogeneic virus-specific T lymphocytes is capable of restoring virus-specific T cell immunity, and are safe and effective in the treatment of viral infections after hematopoietic stem cell transplantation. In this article, we review the emerging role of virus-specific T cell therapy in the management of CMV and BKV after kidney transplantation. On the basis of the available data, virus-specific T cell therapy may be a promising addition to the antiviral treatment armamentarium after kidney transplantation. Future studies are needed to more clearly define the efficacy and risks of virus-specific T cell therapy in the kidney transplant population.
Topics: BK Virus; Cytomegalovirus; Hematopoietic Stem Cell Transplantation; Humans; Kidney Transplantation; Transplant Recipients
PubMed: 35373059
DOI: 10.34067/KID.0001572021 -
Clinical Transplantation Nov 2022BK polyomavirus-associated nephropathy (BKPyVAN) carries a risk of irreversible allograft injury. While detection of BK viremia and biopsy assessment are the current...
BACKGROUND
BK polyomavirus-associated nephropathy (BKPyVAN) carries a risk of irreversible allograft injury. While detection of BK viremia and biopsy assessment are the current diagnostic gold standard, the diagnostic value of biomarkers reflecting tissue injury (donor-derived cell-free DNA [dd-cfDNA]) or immune activation (C-X-C motif chemokine ligand [CXCL]9 and CXCL10) remains poorly defined.
METHODS
For this retrospective study, 19 cases of BKPyVAN were selected from the Vienna transplant cohort (biopsies performed between 2012 and 2019). Eight patients with T cell-mediated rejection (TCMR), 17 with antibody-mediated rejection (ABMR) and 10 patients without polyomavirus nephropathy or rejection served as controls. Fractions of dd-cfDNA were quantified using next-generation sequencing and CXCL9 and CXCL10 were detected using multiplex immunoassays.
RESULTS
BKPyVAN was associated with a slight increase in dd-cfDNA (median; interquartile range: .38% [.27%-1.2%] vs. .21% [.12%-.34%] in non-rejecting control patients; p = .005). Levels were far lower than in ABMR (1.2% [.82%-2.5%]; p = .004]), but not different from TCMR (.54% [.26%-3.56%]; p = .52). Within the BKPyVAN cohort, we found no relationship between dd-cfDNA levels and the extent of tubulo-interstitial infiltrates, BKPyVAN class and BK viremia/viruria, respectively. In some contrast to dd-cfDNA, concentrations of urinary CXCL9 and CXCL10 exceeded those detected in ABMR, but similar increases were also found in TCMR.
CONCLUSION
BKPyVAN can induce moderate increases in dd-cfDNA and concomitant high urinary excretion of chemokines, but this pattern may be indistinguishable from that of TCMR. Our results argue against a significant value of these biomarkers to reliably distinguish BKPyVAN from rejection.
Topics: Humans; BK Virus; Retrospective Studies; Graft Rejection; Cell-Free Nucleic Acids; Kidney Transplantation; Polyomavirus Infections; Kidney Diseases; Viremia; Antibodies; Biomarkers
PubMed: 35894263
DOI: 10.1111/ctr.14785 -
American Journal of Transplantation :... Sep 2019
Topics: BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Humans; Polyomavirus Infections; Viremia
PubMed: 31306544
DOI: 10.1111/ajt.15531 -
Viruses Jan 2022Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for... (Review)
Review
Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for an oHSV for melanoma, but barriers to this promising therapy still exist that limit efficacy. The process of infection, replication and transmission of oHSV in solid tumors is key to obtaining a good lytic destruction of infected cancer cells to kill tumor cells and release tumor antigens that can prime anti-tumor efficacy. Intracellular tumor cell signaling and tumor stromal cells present multiple barriers that resist oHSV activity. Here, we provide a review focused on oncolytic HSV and the essential viral genes that allow for virus replication and spread in order to gain insight into how manipulation of these pathways can be exploited to potentiate oHSV infection and replication among tumor cells.
Topics: Animals; Cell Line, Tumor; Herpes Simplex; Herpesvirus 1, Human; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tropism; Virus Replication
PubMed: 35062322
DOI: 10.3390/v14010118 -
Journal of Clinical Microbiology Sep 2022Quantitative testing of BK virus (BKPyV) nucleic acid has become the standard of care in transplant patients. While the relationship between interassay harmonization and...
Quantitative testing of BK virus (BKPyV) nucleic acid has become the standard of care in transplant patients. While the relationship between interassay harmonization and commutability has been well characterized for other transplant-related viruses, it has been less well studied for BKPyV, particularly regarding differences in commutability between matrices. Here, interassay agreement was evaluated among six real-time nucleic acid amplification tests (NAATs) and one digital PCR (dPCR) BKPyV assay. Differences in the commutability of three quantitative standards was examined across all assays using a variety of statistical approaches. Panels, including 40 samples each of plasma and urine samples previously positive for BKPyV, together with one previously negative plasma sample and four previously negative urine samples, were tested using all assays, with each real-time NAAT utilizing its usual quantitative calibrators. Serial dilutions of WHO, National Institute for Standards and Technology (NIST), and commercially produced (Exact/Bio-Rad) reference materials were also run by each assay as unknowns. The agreement of the clinical sample values was assessed as a group and in a pairwise manner. The commutability was estimated using both relativistic and quantitative means. The quantitative agreement across assays in the urine samples was within a single log unit across all assays, while the results from the plasma samples varied by 2 to 3 log IU/mL. The commutability showed a similar disparity between the matrices. Recalibration using international standards diminished the resulting discrepancies in some but not all cases. Differences in the sample matrix can affect the commutability and interassay agreement of quantitative BKPyV assays. Differences in commutability between matrices may largely be due to factors other than those such as amplicon size, previously described as important in the case of cytomegalovirus. Continued efforts to standardize viral load measurements must address multiple sources of variability and account for differences in assay systems, quantitative standards, and sample matrices.
Topics: BK Virus; Cytomegalovirus; Humans; Nucleic Acids; Reference Standards; Viral Load
PubMed: 35997500
DOI: 10.1128/jcm.00555-22