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Pediatric Nephrology (Berlin, Germany) Sep 2007Polyomavirus-associated nephropathy is diagnosed in 2-8% of pediatric renal transplants and often precedes renal allograft dysfunction. Without intervention, however,... (Review)
Review
Polyomavirus-associated nephropathy is diagnosed in 2-8% of pediatric renal transplants and often precedes renal allograft dysfunction. Without intervention, however, significant graft dysfunction is observed in more than 50% of cases, although progressive early graft loss is reported in only three of 32 (9%) of cases. No specific treatment is available, but early decrease in immunosuppression is followed by declining human polyomavirus type 1 (BK virus) replication and improved outcome. The data suggest differences between pediatric and adult kidney transplantation. Possibly, pediatric patients might be able to mount a more vigorous BK virus-specific immune response than adult patients under similar modulation of immunosuppression. Also the role of cidofovir and leflunomide is still unresolved in pediatric patients. Larger prospective trials are needed to better define the impact of BK virus immunity for replication and disease as well as the role of reducing immunosuppression with or without cidofovir or leflunomide in pediatric transplant patients.
Topics: BK Virus; Child; Humans; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Tumor Virus Infections; Virus Replication
PubMed: 17377822
DOI: 10.1007/s00467-007-0462-x -
Seminars in Cancer Biology Aug 2009BK virus (BKV) is a polyomavirus that ubiquitously infects the human population. Following a typically subclinical primary infection, BKV establishes a life-long... (Review)
Review
BK virus (BKV) is a polyomavirus that ubiquitously infects the human population. Following a typically subclinical primary infection, BKV establishes a life-long persistent infection in the kidney and urinary tract. BKV is known to reactivate and cause severe disease in immunosuppressed patients, particularly renal and bone marrow transplant patients. Infection of BKV in rodent animal models or cells in culture often results in tumor formation or transformation, respectively. When co-expressed with activated oncogenes, BKV large tumor antigen drives the transformation of primary human cells. An etiological role of BKV in human cancer, however, remains controversial. Multiple reports have demonstrated conflicting results in regards to the presence of BKV sequences and/or proteins in various tumor types. This review compiles the most recent findings of BKV detection in a number of human cancers. Due to the lack of conclusive causality data from these studies, there does not appear to be a definitive association between BKV and human cancers.
Topics: Animals; BK Virus; Humans; Neoplasms; Polyomavirus Infections; Tumor Virus Infections
PubMed: 19505653
DOI: 10.1016/j.semcancer.2009.02.004 -
International Journal of Molecular... Dec 2023Polyomaviruses are widespread, with BK viruses being most common in humans who require immunosuppression due to allotransplantation. Infection with BK polyomavirus (BKV)...
Polyomaviruses are widespread, with BK viruses being most common in humans who require immunosuppression due to allotransplantation. Infection with BK polyomavirus (BKV) may manifest as BK virus-associated nephropathy and hemorrhagic cystitis. Established diagnostic methods include the detection of polyomavirus in urine and blood by PCR and in tissue biopsies via immunohistochemistry. In this study, 79 patients with pathological renal retention parameters and acute kidney injury (AKI) were screened for BK polyomavirus replication by RNA extraction, reverse transcription, and virus-specific qPCR in urine sediment cells. A short fragment of the VP2 coding region was the target of qPCR amplification; patients with (n = 31) and without (n = 48) a history of renal transplantation were included. Urine sediment cell immunofluorescence staining for VP1 BK polyomavirus protein was performed using confocal microscopy. In 22 patients with acute renal injury, urinary sediment cells from 11 participants with kidney transplantation (KTX) and from 11 non-kidney transplanted patients (nonKTX) were positive for BK virus replication. BK virus copies were found more frequently in patients with AKI stage III (n = 14). Higher copy numbers were detected in KTX patients having experienced BK polyoma-nephropathy (BKPyVAN) in the past or diagnosed recently by histology (5.6 × 10-3.1 × 10). One patient developed BK viremia following delayed graft function (DGF) with BK virus-positive urine sediment. In nonKTX patients with BK copies, decoy cells were absent; however, positive staining of cells was found with epithelial morphology. Decoy cells were only found in KTX patients with BKPyVAN. In AKI, damage to the tubular epithelium itself may render the epithelial cells more permissive for polyoma replication. This non-invasive diagnostic approach to assess BK polyomavirus replication in urine sediment cells has the potential to identify KTX patients at risk for viremia and BKPyVAN during AKI. This method might serve as a valuable screening tool for close monitoring and tailored immunosuppression decisions.
Topics: Humans; BK Virus; Viremia; Kidney Transplantation; Kidney; Polyomavirus; Polyomavirus Infections; Acute Kidney Injury
PubMed: 38139342
DOI: 10.3390/ijms242417511 -
Annals of Agricultural and... Sep 2017Colorectal cancer is one of the most common cancers worldwide. In Poland, it is the second most common cancer, regardless of gender. The aim of study was to analyze the...
INTRODUCTION AND OBJECTIVE
Colorectal cancer is one of the most common cancers worldwide. In Poland, it is the second most common cancer, regardless of gender. The aim of study was to analyze the incidence of HPV and BKV in the tissue of colorectal cancer and to determine the relationship between the presence of these viruses and the development of this cancer.
MATERIAL AND METHODS
The experiments were conducted using 50 colorectal cancer tissues collected from histological sections. The clinical material was embedded in paraffin blocks. Next, DNA extraction was performed. Isolates of colorectal cancer tissue were tested for the presence of HPV DNA. BKV DNA was detected by PCR using specific primers and then differentiated from JCV by digestion with BamHI enzyme.
RESULTS
In clinical specimens taken from patients with colorectal cancer, HPV DNA was detected in 20% of cases. In 10% of cases the presence of HPV type 18 was confirmed, in the other 90% of the samples HPV type 16 was detected, while the presence of BKV was confirmed in 30% of cases. Coinfection with HPV and BKV was shown in 12% of patients. In one case, BK virus coexisted with HPV type 18, in the remaining 5 cases with HPV type 16.
CONCLUSIONS
Developing colorectal cancer can show no symptoms, even for many years. This is why it is so important to become familiar with as many etiological factors as possible. The development of many human neoplasms is often initiated by exposure to infectious agents - such as bacterial or viral infections. Similar to the human papillomavirus, the BK virus was detected in clinical specimens. It seems that HPV and BKV infections can contribute to the neoplastic process, which requires detailed studies on a larger group of patients.
Topics: Adult; Aged; BK Virus; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Polyomavirus Infections
PubMed: 28954487
DOI: 10.26444/aaem/74648 -
Experimental and Clinical... Feb 2021BK polyomavirus can infect healthy individuals; however, in renal transplant recipients, it can cause nephropathy, which can lead to renal allograftfailure. There are... (Comparative Study)
Comparative Study
OBJECTIVES
BK polyomavirus can infect healthy individuals; however, in renal transplant recipients, it can cause nephropathy, which can lead to renal allograftfailure. There are currently no effective antiviral agents against BK polyomavirus. Surveillance after kidney transplant for BK polyomavirus is the only means to prevent allograft failure. Transplant centers routinely screen for BK polyomavirus in either urine or blood. If BK polyomavirus replication occurs, itis usually detected first in urine, which is followed by detection in blood in a subset of cases. Screening for BK polyomavirus in urine has the potential for earlier detection of viralreactivation.However, not all patients with BK polyomavirus in urine will progress to BK viremia. Therefore, adding urine screening could increase the cost oftests without a clear clinical benefit.
MATERIALS AND METHODS
We conducted an analysis of BK polyomavirus screening methods at 2 different centers and compared their clinical outcomes and efficiency of testing.
RESULTS
We analyzed 209 patientswith BK polyomavirus reactivation after kidney transplant at 2 different institutions from 2008 to 2018. BK polyomavirus reactivation in blood was detected earlierifthe patient was screened by urine screening protocol. However, measurable clinical outcomes were similarin all groups with different screening methods.
CONCLUSIONS
Although screening for BK polyomavirus in urine did detect viralreactivation earlier,there were no differences in graft or clinical outcomes when either the urine or blood screening method was used.
Topics: BK Virus; Humans; Kidney; Kidney Transplantation; Polyomavirus Infections; Viremia; Virus Activation
PubMed: 31801449
DOI: 10.6002/ect.2019.0295 -
Experimental and Clinical... Jan 2020The main function of HLA is to present antigens to lymphocytes and to initiate specific immune responses. Autoimmune, viral, allergic, and neurologic diseases have been...
OBJECTIVES
The main function of HLA is to present antigens to lymphocytes and to initiate specific immune responses. Autoimmune, viral, allergic, and neurologic diseases have been found to be related to HLA molecules. In renal transplant, the main target of the recipient's immune system is the HLA molecules on the surface of donor cells. HLA also plays a role in the development of an immune response to viral infections. After renal transplant, BK virus infections may occur due to immunosuppression. Here, we investigated the relationship between HLA and BK virus in renal transplant recipients.
MATERIALS AND METHODS
This retrospective study investigated HLA-A, HLA-B, and HLA-DR tissue typing before renal transplant. DNA was isolated from whole blood, and tissue typing tests were performed based on polymerase chain reaction. Patients were tested for BK virus posttransplant using DNA isolated from urine and/or plasma samples.
RESULTS
We found HLA-B*13 allele to be a protective factor (P < .049; odds ratio: 0.131; 95% confidence interval, 0.017-1.029) and HLA-DRB1*03 allele to be a possible risk factor (P < .029; odds ratio: 2.521; 95% confidence interval, 1.157-5.490) against BK virus. No significant relationships were found between BK virus and age, sex, donor type, and HLA mismatch.
CONCLUSIONS
HLA class I molecules are known to be effective against viruses with the help of cytotoxic T cells. HLA-B*13 alleles within the HLA class I molecules were identified as protective factors against BK virus. HLA class II is associated with CD4-positive T cells that help secrete immune system cytokines, playing a role in stimulating and suppressing the immune system. We demonstrated that HLA-DRB1*03 allele could be a risk factor against BK virus. This allele may be associated with immunomodulatory cytokine secretion of the immune system.
Topics: BK Virus; DNA, Viral; Female; Gene Frequency; HLA Antigens; Host-Pathogen Interactions; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Male; Opportunistic Infections; Polyomavirus Infections; Retrospective Studies; Treatment Outcome; Tumor Virus Infections; Viral Load
PubMed: 32008495
DOI: 10.6002/ect.TOND-TDTD2019.O24 -
Transplantation Nov 2016BK polyomavirus is ubiquitous, with a seropositivity rate of over 75% in the adult population. Primary infection is thought to occur in the respiratory tract, but... (Review)
Review
BK polyomavirus is ubiquitous, with a seropositivity rate of over 75% in the adult population. Primary infection is thought to occur in the respiratory tract, but asymptomatic BK virus latency is established in the urothelium. In immunocompromised host, the virus can reactivate but rarely compromises kidney function except in renal grafts, where it causes a tubulointerstitial inflammatory response similar to acute rejection. Restoring host immunity against the virus is the cornerstone of treatment. This review covers the virus-intrinsic features, the posttransplant microenvironment as well as the host immune factors that underlie the pathophysiology of polyomavirus-associated nephropathy. Current and promising therapeutic approaches to treat or prevent this complication are discussed in relation to the complex immunopathology of this condition.
Topics: BK Virus; Dendritic Cells; Humans; Immunity, Innate; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Risk Factors; Tumor Virus Infections; Viral Proteins; Virus Activation; Virus Latency
PubMed: 27391196
DOI: 10.1097/TP.0000000000001333 -
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 -
Intervirology 2021Members of the Polyomaviridae family, BK virus (BKV), and John Cunningham virus (JCV) are linked to polyomavirus-associated nephropathy-associated transplant rejection...
BACKGROUND
Members of the Polyomaviridae family, BK virus (BKV), and John Cunningham virus (JCV) are linked to polyomavirus-associated nephropathy-associated transplant rejection in immunodeficient patients.
OBJECTIVE
The aim of the study was to evaluate the prevalence of BKV and JCV in immunocompetent individuals in the north of Iran.
METHODS
Ninety-one urine samples were obtained from renal transplant recipients with a mean age of 39.78 ± 11.19 years. A healthy control group of 65 volunteers with an average age of 40.32 ± 10.7 years also contributed. After DNA extraction, positive cases were detected through PCR. Genotyping was done by alignment and phylogenetic tree construction of the VP1 region against all known JCV and BKV genotypes.
RESULTS
The prevalence of BKV and JCV was 15.38 and 19.78%, respectively. JCV was detected in 7.69% of the control group. The prevalence of the BKV between the case and control groups was significant (p < 0.0001). There was no significant association between BKV and JCV and duration of dialysis (p > 0.05). Overall, 62.16% of JCV cases were genotype I. Besides, genotype II was dominant within patients with BKV-positive patients.
DISCUSSION
The results obtained here show a relatively lower prevalence of BKV and JCV in immunocompromised renal transplant receivers and healthy control than those reported from other areas in Iran. JCV genotyping was evaluated for the first time in Iran. Genotype I for JCV and genotype II for BKV were dominant genotypes in the north of Iran.
Topics: Adult; BK Virus; Caspian Sea; DNA, Viral; Humans; JC Virus; Kidney Transplantation; Middle Aged; Phylogeny; Polyomavirus Infections; Transplant Recipients; Tumor Virus Infections
PubMed: 33596566
DOI: 10.1159/000513369 -
American Journal of Transplantation :... Feb 2010A 1-year, single-center, randomized trial demonstrated that the calcineurin inhibitor or adjuvant immunosuppression, independently, does not affect BK-viruria or viremia...
A 1-year, single-center, randomized trial demonstrated that the calcineurin inhibitor or adjuvant immunosuppression, independently, does not affect BK-viruria or viremia and that monitoring and pre-emptive withdrawal of immunosuppression was associated with resolution of BK-viremia and absence of clinical BK-nephropathy without acute rejection or graft loss. A retrospective 5-year review of this trial was conducted. In cases of BK viremia, the antimetabolite was withdrawn and for sustained viremia, the calcineurin inhibitor was minimized. Five-year follow-up was available on 97% of patients. Overall 5-year patient survival was 91% and graft survival was 84%. There were no differences in patient-survival by immunosuppressive regimen or presence of BK-viremia. Immunosuppression and viremia did not influence graft survival. Acute rejection occurred in 12% by 5-years after transplant, was less common with tacrolimus versus cyclosporine (9% vs. 18%; p = 0.082), and was lowest with the tacrolimus-azathioprine regimen (5%, p = 0.127). Tacrolimus was associated with better renal function at 5-years (eGFR 63 FK vs. 52 CsA mL/min, p = 0.001). Minimization of immunosuppression upon detection of BK-viremia was associated with excellent graft survival at 5-years, low rejection rates and excellent renal function. It is a safe, short and long-term strategy that resulted in freedom from clinically evident BK-virus nephropathy.
Topics: Azathioprine; BK Virus; Cyclosporine; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Diseases; Kidney Function Tests; Tacrolimus; Viremia
PubMed: 20055811
DOI: 10.1111/j.1600-6143.2009.02952.x