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BK polyomavirus infection is an important cause of graft loss in transplant patients, however, currently available therapies lack effectiveness against this pathogen. Identification of immunological targets for potential treatments is therefore necessary. The aim of this study was to predict candidates of immunodominant epitopes within four BK virus proteins (VP1, VP2, VP3 and LTA) using PBMCs from 44 healthy donors. We used the ELISpot epitope mapping method to evaluate the T‐cell response, and HLA‐peptide binding was predicted using the NetMHCpan algorithm. A total of 11 potential peptides were selected for VP1, 3 for VP2/VP3 and 13 for LTA. Greater reactivity was observed for VP1 and LTA proteins compared with VP2/VP3. Most of the peptides selected as potential immunodominant candidates were restricted towards several HLA class I and II alleles, with predominant HLA class I binding by computational predictions. Based on these findings, the sequences of the selected immunodominant epitopes candidates and their corresponding HLA restrictions could contribute to the optimisation of functional assays and aid in the design and improvement of immunotherapy strategies against BK virus infections. [ABSTRACT FROM AUTHOR]

The article "Transplant Trial Watch" discusses a study on heart transplant recipients comparing outcomes of everolimus versus a standard regimen. The study followed participants for 12 years and found a significant benefit in renal function for the everolimus group. Another study in the article focuses on a novel monoclonal antibody, MAU868, targeting BK polyomavirus VP1, showing promising results in safety and tolerability. These studies offer potential advancements in heart transplantation and BK virus treatment, respectively. [Extracted from the article]

Purpose A case of BK nephropathy in a kidney transplant recipient who received an organ from a hepatitis C virus (HCV)–positive donor is reported. Summary A 66-year-old male negative for HCV with chronic kidney disease secondary to diabetic glomerulosclerosis received a kidney transplant from an HCV-viremic donor. His initial postoperative course was uncomplicated, and HCV treatment with glecaprevir/pibrentasvir was initiated after discharge. On postoperative day (POD) 60, the patient developed BK viremia and his mycophenolate mofetil dose was decreased. Over the next few months, the BK viral load increased, with mycophenolate mofetil stopped and the tacrolimus goal lowered in response. On POD 130, the patient was admitted for a hypertensive crisis and found to have decreased renal function. During this hospitalization, the patient received a course of intravenous immune globulin (IVIG). Despite an initial response to the modification of immunosuppression therapy and several courses of IVIG over the following months, the patient's renal function continued to decline. At 18 months after transplantation, the patient was restarted on dialysis and taken off all immunosuppression. Conclusion Utilization of organs from HCV-positive donors in HCV-negative recipients allows for expansion of the donor pool and facilitates shorter times on the waitlist. Although initial data in HCV-discordant transplantation did not find an increased risk for opportunistic infections, more recent studies have shown that such risk may be present. This case report describes a patient who developed BK viremia and eventual allograft failure after an HCV-discordant transplantation. [ABSTRACT FROM AUTHOR]

Aims and Objectives: The aim was to assess the prevalence and treatment of BK virus nephropathy (BKVN) in patients who underwent renal transplantation at a single center in South India with a 1-year follow-up analysis. To assess the efficacy of treatment with intravenous immunoglobulin (IvIg) in cases of proven BKVN. Materials and Methods: Three hundred and seventy-one patients underwent renal transplantation from 2018 to 2020. All were screened for BKVN with quantitative serum polymerase chain reaction (PCR) every 3 months for 1 year after transplant. Patients with positive tests underwent renal allograft biopsy. In all patients, antimetabolite was stopped, tacrolimus dose was reduced, and leflunomide was started. All patients with biopsy-proven BKVN were administered IvIg 2 grams/kg over 5 days and had a 1-year follow-up. Results: Fourteen patients had BK viremia; 12 had biopsy-proven BKVN. All were male with a mean age of mean age: 45.3 years ± 14.8 standard deviation (SD). Induction: basiliximab (7) and antithymocyte globulin (ATG) (7). Maintenance immunosuppression: tacrolimus, enteric-coated mycophenolate mofetil, and prednisolone. The median presentation time was 12 months. Mean graft function: baseline S. Creatinine of 1.32 mg/dL changed to 2.01 mg/dL at diagnosis. The mean presenting BKV PCR (copies/ml) was 44912 ± 56285 SD. No significant differences were observed in time of presentation, severity, mean tacrolimus level, and graft failure between patients receiving basiliximab or ATG. There were two relapses; two grafts failed. Class I BKVN had a better prognosis. Graft survival at 1 year was 85.71%. Conclusions: This is the first South Asian follow-up study of BKVN in kidney transplant recipients treated with IvIg. BKVN was documented in the first 15 months after transplant. There was no increased prevalence of BKVN in patients with ATG. Histopathological class has prognostic relevance with Class I having a better prognosis. Multipronged treatment, including IvIg, leads to 1-year graft survival of 85.71%. Long-term outcomes need follow-up. [ABSTRACT FROM AUTHOR]

These key histopathologic features, in conjunction with immunosuppression due to solid organ transplant and characteristic papules with central spines, were diagnostic of trichodysplasia spinulosa (TS). Keywords: immunosuppression; polyomavirus; transplant; trichodysplasia spinulosa; viral infection EN immunosuppression polyomavirus transplant trichodysplasia spinulosa viral infection 721 723 3 07/17/23 20230701 NES 230701 CASE PRESENTATION A 5-year-old girl with a 1-year history of a heart transplant, on immunosuppression with tacrolimus and mycophenolate mofetil and oral valganciclovir for cytomegalovirus prophylaxis, presented with a papular eruption on her face, trunk, and extremities. The patient was started on topical ammonium lactate 12% lotion daily following biopsy-confirmed diagnosis, with a plan to commence treatment with topical cidofovir pending insurance approval. [Extracted from the article]

• BK polyomavirus infection is not an uncommon complication after kidney transplant. • Male sex, older age, and retransplant are risk factors for BK polyomavirus infection. • Acute rejection is more frequent in patients with history of BK polyomavirus infection. • Stepwise minimization of immunosuppression is the first-line approach in patients with BK polyomavirus infection. • High-level BK viremia negatively impacts on kidney transplant survival. BK polyomavirus infection (BKVi) is an important cause of kidney transplant (KT) loss, but there is scarce evidence on the impact of BK plasma viral load on graft function and long-term KT survival. A retrospective cohort study including all KT recipients with BKVi (BK viremia identified in ≥3 consecutive samples by polymerase chain reaction) in our center from January 2010 to December 2020 was performed. A case-control study (1:2) was performed. We grouped the cases according to their highest peak viral load: low-level viremia (<10,000 copies/mL) and high-level viremia (≥10,000 copies/mL). To identify risk factors for BKVi, a logistic regression analysis was achieved, and a multivariable Cox regression was used to describe risk factors for graft loss. A total of 849 KTs were performed, and 67 presented BKVi (low-level viremia, n = 35 and high-level viremia, n = 26). In logistic regression analysis male sex (odds ratio [OR], 4.226; 95% CI, 1.660-10.758, P =.002), age (OR, 1.047; 95% CI, 1.008-1.088; P =.018), and retransplant (OR, 4.162; 95% CI, 1.018-17.015; P =.047) were predictors of BKVi. Acute rejection was more frequent in the BKVi group (18% vs 4.9%, P =.004), and graft survival was lower in patients with BKVi and high-level viremia (P =.027). In Cox regression analysis, BKVi (hazard ratio, 3.657; 95% CI, 1.146-11.670; P =.029) and specific BKV (BK polyomavirus) high-level viremia (hazard ratio, 1.988; 95% CI, 1.012-3.907; P =.046) were predictors of shorter graft survival. BKV high-level viremia was associated with BKV nephropathy and poorer graft survival. Additionally, acute rejection is more frequent after BKVi. It is necessary to develop strategies safe and effective for these patients. [ABSTRACT FROM AUTHOR]

Background: BK polyomavirus infection results in renal allograft dysfunction, and it is important to find methods of prediction and treatment. As a regulator of host immunity, changes in the gut microbiota are associated with a variety of infections. However, the correlation between microbiota dysbiosis and posttransplant BK polyomavirus infection was rarely studied. Thus, this study aimed to characterize the gut microbiota in BK polyomavirus-infected renal transplant recipients in order to explore the biomarkers that might be potential therapeutic targets and establish a prediction model for posttransplant BK polyomavirus infection based on the gut microbiota. Methods: We compared the gut microbial communities of 25 BK polyomavirus-infected renal transplant recipients with 23 characteristic-matched controls, applying the 16S ribosomal RNA gene amplicon sequencing technique. Results: At the phylum level, Firmicutes / Bacteroidetes ratio significantly increased in the BK polyomavirus group. Bacteroidetes was positively correlated with CD4/CD8 ratio. In the top 20 dominant genera, Romboutsia and Roseburia exhibited a significant difference between the two groups. No significant difference was observed in microbial alpha diversity. Beta diversity revealed a significant difference between the two groups. Nine distinguishing bacterial taxa were discovered between the two groups. We established a random forest model using genus taxa to predict BK polyomavirus infectious status, which achieved the best accuracy (80.71%) with an area under the curve of 0.82. Two genera were included in the best model, which were Romboutsia and Actinomyces. Conclusions: BK polyomavirus-infected patients had gut microbiota dysbiosis in which the Firmicutes / Bacteroidetes ratio increased in the course of the viral infection. Nine distinguishing bacterial taxa might be potential biomarkers of BK polyomavirus infection. The random forest model achieved an accuracy of 80.71% in predicting the BKV infectious status, with Romboutsia and Actinomyces included. [ABSTRACT FROM AUTHOR]

• Screening for polyomavirus infections is an important part of post-transplant care. • Viruria and viremia (DNA-emia) are methods of screening for polyomavirus infection. • JCV, as well as BKV, can cause PVAN and loss of the transplanted kidney. • High level of viruria may be a predictor of polyomavirus replication. • The tacrolimus-based immunosuppression regimen increases the risk of PVAN. Polyomavirus (PV) infection and PV-associated nephropathy (PVAN) are some of the most important problems in kidney transplantation. Our objective was to determine the incidence of PV viruria and PV replication in single-center Polish kidney transplant recipients (KTR). Urine samples from 155 cadaveric KTR were analyzed for PV viruria using quantitative real-time polymerase chain reaction and the patients were followed prospectively. The PV replication was recognized when the urine level was >107 PV DNA copies/mL of urine. Based on the PV DNA analysis, the patients were divided into 3 groups: Group 1 (n = 87; 56.1%) without viruria, Group 2 (n = 44; 28.4%) with viruria but without PV replication, and Group 3 (n =24; 15.5%) with PV replication. The presence of PV viruria was correlated with the type of immunosuppressive regimen, strongly associated with tacrolimus intake. There was no correlation between viruria and mycophenolate daily dose in the study population. In Group 3 there were 6 patients (3.9%) with high viruria (>1010 copies/mL), and 5 patients from this group had confirmed PVAN in allograft biopsy. The prevalence of BK virus infection in KTR is similar to that reported in studies from other countries. We confirmed that PV viruria can be both a good screening for PV infection and a good predictor of PVAN. Tacrolimus was the most important predictor of PV viruria and PV replication in KTR. [ABSTRACT FROM AUTHOR]

Background: Some studies have suggested mizoribine (MZR) could inhibit the replication of BK polyomavirus (BKPyV). The purpose of this study was to explore whether conversion from mycophenolate mofetil (MMF) to MZR in the early stages of BKPyV infection can improve kidney allograft prognosis.Methods: Twenty-one kidney transplant recipients with BKPyV viruria/viremia and ten with BK polyomavirus-associated allograft nephropathy (BKPyVAN) received MZR conversion therapy were retrospectively identified. The clearance rate of urine and blood BKPyV DNA, change of serum creatinine (SCr), uric acid (UA), hemoglobin (HB), white blood cell (WBC), lymphocyte ratio, platelet (PLT), routine urinalysis, panel reactive antibody (PRA), and gastrointestinal disorders during follow-up of the 2 groups were evaluated and compared.Results: After MZR conversion therapy, the clearance rate of urine and blood viral load in BKPyV viruria/viremia group were 85.7 and 100 %, while that in BKPyVAN were 40 and 87.5 %, respectively. Stable SCr were observed in all cases of BKPyV viruria/viremia group, while that of BKPyVAN was only 40 % (P < 0.001) and one even progressed to end-stage renal disease. The results of routine urinalysis in the two groups showed no significant changes before and after MZR conversion therapy. However, in BKPyV viruria/viremia group, four cases developed acute rejection and one had positive PRA-II but no donor specific antibody, requiring conversion back to MMF. Hyperuricemia was the common adverse effect of MZR.Conclusions: Conversion from MMF to MZR could help clear BKPyV infection. As compared to BKPyVAN, patients who underwent initiation of MZR conversion therapy in the early stages of BKPyV infection maintained stable allograft function. Prospective studies with larger sample size are needed to ascertain this preliminary finding. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis and treatment of Polyomavirus BK Nephropathy (PVBKN) is a challenging issue in the management of patients with kidney transplantation. Currently, histopathologic diagnosis is the gold standard method for diagnosis of PVBKN. However, typical viral inclusions may not be found in early stages of the PVBKN and should, instead, be diagnosed using immunohistochemistry (IHC) study. There is no clear consensus about routine IHC tests in the pathologic evaluation of transplanted kidney biopsy samples.Material and Methods: The current study was conducted on transplanted kidney biopsy samples, since 2016 to 2019. The patients who have presented with new onset of allograft dysfunction, at least 2 weeks after transplantation surgery, were included in our study. All these biopsy samples were evaluated with routine renal biopsy stains as well as IHC for SV40 (Simvian Virus 40) antigen. The identification of typical nuclear virus inclusion body and any nuclear positive staining on IHC (≥1+ positive result) were considered as definite evidence of PVBKN. Sensitivity, specificity, Positive Predictive and Negative Predictive Values (PPV and NPV) of histopathologic assessment without IHC study were evaluated.Results: Among 275 included cases, 18 (6.5%) patients with PVBKN were diagnosed. In patients with PVBKN, typical viral inclusions were detected in 14 samples (77.7%), on primary histopathological examination. However, virus-infected cells were identified just after IHC study in 4 (22.2%) of patients. Sensitivity, Specifity, PPV and NPV of morphologic histopathological assay without IHC for detection of PVBKN was 77.7, 100, 100 and 98.4% respectively.Conclusion: Routine IHC study for SV40 in all transplanted kidney biopsy samples with new onset of allograft dysfunction, will enhance the diagnostic sensitivity of early stage disease detection. [ABSTRACT FROM AUTHOR]

BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC. [ABSTRACT FROM AUTHOR]

Background: BK polyomavirus (BKPyV) remains a significant cause of premature kidney transplant failure. In the absence of effective antivirals, current treatments rely on reducing immunosuppression to regain immune control over BKPyV replication. Increasing BKPyV-specific CD8 T cells correlate with clearance of BKPyV DNAemia in kidney transplant patients. We characterized a novel approach for expanding BKPyV-specific CD8 T cells in vitro using 27mer-long synthetic BKPyV peptides, different types of antigen-presenting cells, and CD4 T cells.Methods: Langerhans cells and immature or mature monocyte-derived dendritic cells (Mo-DCs) were generated from peripheral blood mononuclear cells of healthy blood donors, pulsed with synthetic peptide pools consisting of 36 overlapping 27mers (27mP) or 180 15mers (15mP). BKPyV-specific CD8 T-cell responses were assessed by cytokine release assays using 15mP or immunodominant 9mers.Results: BKPyV-specific CD8 T cells expanded using 27mP and required mature Mo-DCs (P = .0312) and CD4 T cells (P = .0156) for highest responses. The resulting BKPyV-specific CD8 T cells proliferated, secreted multiple cytokines including interferon γ and tumor necrosis factor α, and were functional (CD107a+/PD1-) and cytotoxic.Conclusions: Synthetic 27mP permit expanding BKPyV-specific CD8 T-cell responses when pulsing mature Mo-DCs in presence of CD4 T cells, suggesting novel and safe approaches to vaccination and adoptive T-cell therapies for patients before and after kidney transplantation. [ABSTRACT FROM AUTHOR]

Background & Objective: Polyomavirus-associated nephropathy (PVAN), mainly caused by the BK virus, is one of the most important infectious complications of kidney transplantation. The leading histopathologic characteristics of PVAN is viral cytopathic effects, such as nucleomegaly with smudged or clumped chromatin and intranuclear ground-glass inclusion, mostly in tubular epithelial cells. Moreover, tubular necrosis, tubulitis, interstitial inflammation, atrophy, and fibrosis have been noted. Positive immunohistochemistry (IHC) staining for SV-40 highlights the infected epithelial cells of renal tubules. Methods: A total of 85 core needle biopsies of transplanted kidneys were evaluated histologically and were stained for SV-40 using the IHC method. In addition, a followup of graft failure was performed. Results: Our findings revealed that the frequency of polyomavirus infection in kidney transplant patients in the Northeast of Iran is 4.7%. There was no significant correlation between PVAN and graft rejection. Although a higher rate of graft loss was observed in PVAN patients, in comparison with non-PVAN patients (25% vs. 14.8%), the difference was not statistically significant. Moreover, patients with immunohistochemically confirmed PVAN and those with histopathologic features of viral-like cytopathic effects had significantly lower graft survival in the follow-up period (42.5 vs. 196.8 months and 109.4 vs. 205.7 months, respectively). Conclusion: The frequency of polyomavirus infection in kidney transplant patients in the Northeast of Iran is 4.7%. There was no significant correlation between PVAN and graft rejection. Furthermore, we observed that polyomavirus infection accelerates the course of graft loss. [ABSTRACT FROM AUTHOR]

Purpose: Polyomavirus nephropathy has been recognized as an important cause of silent loss of kidney transplant function in up to 50% of kidney recipients (1). The present study aimed to evaluate the risk factors associated with BK virus infection in kidney transplant recipients.Materials and Methods: Clinical information, urinary Decoy cells, and blood polymerase chain reaction (PCR) tests were collected for polyomavirus infection in 223 kidney transplant recipients undergoing surgery at Razi hospital at Guilan University of Medical Sciences between 2007 and 2015. Kidney biopsies were performed in patients with BKPyV- DNAemia more than 10,000 Copies/ml or increased plasma creatinine.Results: Among 223 patients, 116 (52%) were male. The mean age of participants was 49.57±13.48 years. Out of 223 participants, 41 (18.4%) had Decoy cells in their urine, and 182 (81.6%) did not, 15 of whom (6.7%) had viral genome in their blood. Only did 3 patients out of 10 have BK Virus nephropathy in their kidney biopsy. Among risk factors, it was found that post-transplant duration (P< 0.001) and the use of anti-thymocyte globulin (P= 0.001) were the most significant risk factors for finding decoy cells in patients' urine.Conclusions: Post-transplant time, particularly the first 6 months, was found as the most important risk factor for the reactivation of polyomavirus infection in our patients because of strong immunosuppression and use of anti-thymocyte globulin (for prophylaxis or rejection treatment). It is concluded that kidney transplant recipients should be monitored in episodically after transplantation. [ABSTRACT FROM AUTHOR]

Aim: BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication in patients after hematopoietic stem cell transplantation (HSCT). The aim of this study was to investigate the incidence of BKV infection in pediatric patients receiving HSCT. Material and Methods: Total of 51 patients aged between 16 months and 16 years old and followed up between October 2015 and September 2017 were included in the study. The patients were monitored by quantitative real-time polymerase chain reaction (Anatolia Geneworks, Turkey) test for the detection of BKV DNA in urine and blood. Results: Of patients, 46 received allogeneic HSCT and 5 autologous HSCT. BKV DNA positivity was detected in urine and/or blood of total 27 (52.9%) patients in whom 26 (56.5%) of 46 patients with allogeneic transplantation, and 1 (20.0%) of 5 patients with autologous transplantation. BKV viral load in urine >107 copies/ml required for preemptive treatment was detected in 12 (26.1%) of 46 patients received allogeneic HSCT. The development of HC was prevented in 9 (75.0%) of the 12 patients given preemptive treatment, while 3 (25.0%) cases developed HC and cured by treatment. BKV viruria was detected >109 copies/ml in two weeks before the onset of HC and was accepted as a prognostic indicator for predictive diagnosis of HC. BKV viremia was found >104 copies/ml in 1 patient within two weeks before the onset of cystitis. Conclusion: Screening for BKV infection, especially BKV viruria in HSCT patients, is recommended for the predictive diagnosis of HC in patients at high risk. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that plasma donor–derived cell-free DNA (dd-cfDNA) can predict renal allograft antibody-mediated rejection. This study was performed to evaluate the value of urine dd-cfDNA concentration and dd-cfDNA fraction (%) for discriminating BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant recipients with urinary BK polyomavirus (BKPyV) infection. Methods: In this retrospective single-center observational study, we enrolled kidney transplant recipients who were diagnosed with urine BKPyV infection between August 2018 and May 2019 at the First Affiliated Hospital of Sun Yat-sen University. Urine dd-cfDNA was measured by using a novel target region capture sequencing methodology. The pathological diagnosis of BKPyVAN was confirmed by anti-SV40-T immunohistochemical staining and classified using the American Society for Transplantation schema. Receiver operating characteristic curve analysis was used to investigate the relations of urine dd-cfDNA and dd-cfDNA% to intrarenal allograft BKPyV infection states. Results: In total, 93 patients were enrolled, including 40 cases of proven BKPyVAN, seven cases of probable BKPyVAN, 23 cases of possible BKPyVAN, and 23 cases of resolving BKPyVAN. Urine dd-cfDNA level in proven BKPyVAN (22.09 ± 21.27 ng/ml) was comparable to that in probable BKPyVAN (15.64 ± 6.73 ng/ml, P = 0.434) but was significantly higher than that in possible BKPyVAN (5.60 ± 3.53 ng/ml) and resolving BKPyVAN (5.30 ± 3.34 ng/ml) (both P s < 0.05). Urine dd-cfDNA% of proven BKPyVAN (0.71 ± 0.21) was lower than that of probable BKPyVAN (0.91 ± 0.04, P < 0.001), but was significantly higher than that of possible BKPyVAN (0.56 ± 0.30) and resolving BKPyVAN (0.46 ± 0.28) (both P s < 0.05). For distinguishing biopsy-proven BKPyVAN from biopsy-excluded BKPyVAN, the discrimination capacity of urine dd-cfDNA (AUC: 0.842, 95% CI: 0.735, 0.918) was superior to that of plasma BKPyV DNA load (AUC: 0.660, 95% CI: 0.537, 0.769) with 0.181 (95% CI: 0.043, 0.319) difference between areas under ROC curves (P = 0.010). Conclusion: The elevated urine dd-cfDNA level may help discriminate BKPyVAN in kidney transplant recipients with BKPyV viruria. [ABSTRACT FROM AUTHOR]

Background: BK virus-associated nephropathy (BKVAN) is a relatively common cause of renal dysfunction in the first six months after renal transplantation. It arises from reactivation of the latent and usually harmless BK virus (BK virus) due to immunosuppression and other factors including some that are unique to renal transplantation such as allograft injury. BKVAN is much rarer in non-renal solid organ transplantation, where data regarding diagnosis and management are extremely limited.Case Presentation: We report a case of a 58-year-old man found to have worsening renal dysfunction nine months after bilateral sequential lung transplantation for chronic obstructive pulmonary disease (COPD). He had required methylprednisolone for acute allograft rejection but achieved good graft function. Urine microscopy and culture and renal ultrasound were normal. BK virus PCR was positive at high levels in urine and blood. Renal biopsy subsequently confirmed BKVAN. The patient progressed to end-stage renal failure requiring haemodialysis despite reduction in immunosuppression, including switching mycophenolate for everolimus, and the administration of intravenous immunoglobulin (IVIG).Conclusions: This very rare case highlights the challenges presented by BK virus in the non-renal solid organ transplant population. Diagnosis can be difficult, especially given the heterogeneity with which BKV disease has been reported to present in such patients, and the optimal approach to management is unknown. Balancing reduction in immunosuppression against prevention of allograft rejection is delicate. Improved therapeutic options are clearly required. [ABSTRACT FROM AUTHOR]

Background: Several DNA viruses are highly suspicious to have oncogenic effects in humans. This study investigates the presence of potentially oncogenic viruses such as SV40, JCV, BKV and EBV in patient-derived colorectal carcinoma (CRC) cells typifying all molecular subtypes of CRC.Methods: Sample material (gDNA and cDNA) of a total of 49 patient-individual CRC cell lines and corresponding primary material from 11 patients, including normal, tumor-derived and metastasis-derived tissue were analyzed for sequences of SV40, JVC, BKV and EBV using endpoint PCR. In addition, the susceptibility of CRC cells to JCV and BKV was examined using a long-term cultivation approach of patient-individual cells in the presence of viruses.Results: No virus-specific sequences could be detected in all specimens. Likewise, no morphological changes were observed and no evidence for viral infection or integration could be provided after long term CRC cell cultivation in presence of viral particles.Conclusions: In summary, the presented data suggest that there is no direct correlation between tumorigenesis and viral load and consequently no evidence for a functional role of the DNA viruses included into this analysis in CRC development. [ABSTRACT FROM AUTHOR]

Prevention and early detection of BK polyomavirus (BKV) infection is important for long-term kidney graft survival; hence, pretransplant screening methods are essential to identify recipients at high risk for BKV infection. This study investigated the association of pretransplant donor and recipient BKV antibody status with the occurrence of post-transplant BKV infection. We prospectively enrolled 47 adult living donor kidney transplant pairs from December 2014 to January 2016. Recipient and donor pretransplant BKV antibody titer was measured by hemagglutination inhibition (HI) test. Donor and recipient median HI titer of 1:20 was used as a cutoff to define seropositivity. Recipients were divided into 2 groups (BKV antibody donor-seropositive/recipient-seronegative (D+/R-) and non-D+/R-). Urinary cytology was used to screen for BKV infection. Plasma polymerase chain reaction testing for BKV DNA was used when decoy cells in urine were persistently detected. Nine (19.2%) of 47 patients belonged to the D+/R- group. Decoy cells were observed in 32 recipients (68.1%) during follow-up. BK viremia occurred in 3 (6.4%) cases. The maximum decoy cell count was significantly higher in the D+/R- group than in the non-D+/R- group (P =.0002). Decoy-cell-free survival was significantly shorter in the D+/R- group (P =.0220). Multivariate analysis identified only BKV antibody serostatus as an independent risk factor for decoy cell appearance (P =.0491). Pretransplant donor and recipient BKV antibody status was associated with higher maximum decoy cell count and shorter decoy-cell-free survival after kidney transplantation. • BK polyomavirus (BKV) antibody serostatus (donor-seropositive/recipient-seronegative [D+/R-]) is associated with a high maximum decoy cell count. • BKV antibody serostatus D+/R- is associated with short decoy-cell-free survival. • A high maximum decoy cell count is associated with short decoy-cell-free survival. [ABSTRACT FROM AUTHOR]

Background: Published literature on predictors of polyomavirus (BKV) and cytomegalovirus (CMV) infections in simultaneous pancreas and kidney (SPK) transplant and their impact on allograft outcomes remain sparse. We hypothesize that BKV and CMV viremia infections decrease allograft survival in SPK. Identifying modifiable predictors of BKV and CMV may help tailor immunosuppression and improve allograft survival. Methods: All SPK recipients at our institution between January 2000 and April 2016 were included (n = 757). Thirty‐nine recipients had BKV only and 25 had CMV only, and infection occurred at median follow‐up times of 217 and 163 days, respectively. Event density sampling was used to match recipients with BKV or CMV to up to 10 recipients without infection by age, sex, and HLA mismatch status, and these were followed for a median of 4.3 years after infection. Results: Older age (HR 1.49 for each decade; 95% CI: 0.95, 2.35; P =.083) and tacrolimus use (HR 20.6; 95% CI: 2.37, 179.53; P =.006) were associated with increased incidence of BKV, but not CMV, infection. Both BKV and CMV infections were associated with increased risk of allograft failure for both pancreas (BKV [HR 2.17; 95% CI 1.47, 3.208; P =.000], CMV [HR 1.7; 95% CI 1.077, 2.687; P =.023]) and kidney (BKV [HR 2.65; 95% CI 1.765, 3.984; P =.000], CMV [HR 2.07; 95% CI 1.295, 3.308; P =.002]). Conclusion: Older age at time of transplant and tacrolimus may help predict BKV infection in SPK recipients. [ABSTRACT FROM AUTHOR]

Background: BK virus hemorrhagic cystitis (BKV-HC) is a common complication following hematopoietic stem cell transplant (HSCT); optimal management remains uncertain. Supportive care (bladder irrigation and blood transfusions) and intravenous and intravesicular cidofovir have all been used with varying success. Objective: The purpose of this study was to determine the safety and effectiveness of intravesicular cidofovir for BKV-HC following HSCT. Methods: A retrospective analysis of all HSCT patients with BKV-HC prescribed intravesicular cidofovir from 2012 to 2017. Results: 33 patients were treated for BKV-HC. The median age was 50 years (range 23-73), and 18 (55%) were male. The median HC symptom severity was 2, with a median BK urine viral load pretreatment of 100,000,000 IU/mL. Patients received a median of 2 intravesicular treatments (range 1-7) at a dosage of 5 mg/kg per instillation. In all, 19 (59%) patients demonstrated complete clinical resolution of symptoms; 9 (28%) had a partial response; and 4 (13%) had no change in symptoms. Patients with a high pretreatment BK viral load (>100 million) and high HC grade (2-4) had a lower frequency of complete remission. The main side effect of intravesicular instillation was severe bladder spasms in 4 patients (12%). Conclusion and Relevance: This is the largest study of intravesicular cidofovir treatment of BKV HC reported to date; 88% of patients with BVK-HC achieved clinical improvement of symptoms with minimal side effects. Clinical trials of intravesicular cidofovir could provide further evidence for this treatment for BKV-HC. [ABSTRACT FROM AUTHOR]

I was privileged in 2019 to receive the Astellas Practice Development Travel Grant which allowed me the opportunity to attend the American Transplant Congress (ATC) and the Transplant Infectious Diseases (TID) Symposium in Boston, USA. In addition, I was able to attend several reserved offsite meetings with international experts in the fields of transplant infectious diseases and transplant frailty. This included a supernumerary clinical attachment to the University of Pittsburgh Medical Centre Abdominal Transplant Unit and the attached Thomas E Starzl Transplantation Institute. This paper summarises highlights which I think will be interesting and educational for colleagues, and provides reflections on several informative and clinically valuable interviews and observations during this experience. I hope to also encourage members of the TNA to embrace the opportunity to apply for this generous practice development grant. [ABSTRACT FROM AUTHOR]

Objectives: To review rare cases of BK polyomavirus (BKPyV) associated urologic carcinomas in kidney transplant recipients at one institution and in the literature.Methods: We describe the clinicopathologic features of BKPyV-associated urologic carcinomas in a single-institution cohort.Results: Among 4,772 kidney recipients during 1994 to 2014, 26 (0.5%) and 26 (0.5%) developed posttransplantation urothelial carcinomas (UCs) and renal cell carcinomas (RCCs), respectively, as of 2017. Six (27%) UCs but none of the RCCs expressed large T antigen (TAg). TAg-expressing UCs were high grade with p16 and p53 overexpression (P < .05 compared to TAg-negative UCs). Tumor genome sequencing revealed BKPyV integration and a lack of pathogenic mutations in 50 cancer-relevant genes. Compared to TAg-negative UCs, TAg-expressing UCs more frequently presented at advanced stages (50% T3-T4) with lymph node involvement (50%) and higher UC-specific mortality (50%).Conclusions: Post-renal transplantation BKPyV-associated UCs are aggressive and genetically distinct from most non-BKPyV-related UCs. [ABSTRACT FROM AUTHOR]

The article describes the evaluation and management of BK polyomavirus (BKV) viremia in a 2001 and 2014 heart transplant recipients, with topics mentioned such as BKV-associated nephropathy, renal failure, and polymerase chain reaction.

We report a case of primary trichodysplasia spinulosa (TS) infection in a kidney transplant child and describe for the first time the presence of degenerated TS‐associated polyomavirus (TSPyV)‐infected cells in a TS patient's urine that are morphologically different from BK or JC polyomavirus‐infected decoy cells. [ABSTRACT FROM AUTHOR]

Since its discovery in 1971, BK Polyomavirus infection has been increasingly recognized, especially since the introduction of more effective immunosuppressive medications in the early 1990s. BK virus is believed to have a high seroprevalence in healthy individuals, entering a latent phase in the genitourinary that follows the primary infection. Reactivation may occur in immunocompromised hosts, with significant effects seen especially in kidney and hematopoietic stem cell transplant recipients. Screening methods have been developed and are implemented as early detection may allow for the prevention of irreversible tissue damage. Reduction of immunosuppression remains the cornerstone of therapy for BKV infection, and adjunctive therapies have shown variable results. Newer cellular-based therapeutics might provide a more targeted treatment for BKV infection but are still in need of more randomized human studies. [ABSTRACT FROM AUTHOR]

BK polyomavirus (BKPyV) is a small DNA virus that establishes a life-long persistent infection in the urinary tract of most people. BKPyV is known to cause severe morbidity in renal transplant recipients and can lead to graft rejection. The simple 5.2-kbp double-stranded DNA (dsDNA) genome expresses just seven known proteins; thus, it relies heavily on the host machinery to replicate. How the host proteome changes over the course of infection is key to understanding this host-virus interplay. Here, for the first time quantitative temporal viromics has been used to quantify global changes in >9,000 host proteins in two types of primary human epithelial cells throughout 72 h of BKPyV infection. These data demonstrate the importance of cell cycle progression and pseudo-G2 arrest in effective BKPyV replication, along with a surprising lack of an innate immune response throughout the whole virus replication cycle. BKPyV thus evades pathogen recognition to prevent activation of innate immune responses in a sophisticated manner. IMPORTANCE BK polyomavirus can cause serious problems in immune-suppressed patients, in particular, kidney transplant recipients who can develop polyomavirus-associated kidney disease. In this work, we have used advanced proteomics techniques to determine the changes to protein expression caused by infection of two independent primary cell types of the human urinary tract (kidney and bladder) throughout the replication cycle of this virus. Our findings have uncovered new details of a specific form of cell cycle arrest caused by this virus, and, importantly, we have identified that this virus has a remarkable ability to evade detection by host cell defense systems. In addition, our data provide an important resource for the future study of kidney epithelial cells and their infection by urinary tract pathogens. [ABSTRACT FROM AUTHOR]

Objective: To investigate the characteristics of BK virus (BKV) specific cellular immune response in the recipients who have early infection with BKV after renal transplantation.Methods: The recipients of renal allografts (n = 30) were divided into groups of BK virus nephropathy (BKVN), viruria, and viremia. The BKV load was observed with real-time fluorescence quantitative polymerase chain reaction in urine and blood every three months. The values of serum creatinine (SCr) were detected. The peripheral blood mononuclear cells (PBMCs) were cultivated with overlapping peptide pool containing BKV structural proteins VP1, VP2, and VP3, and regulatory proteins large tumor antigen (LT-Ag) and small tumor antigen (st-Ag), to stimulate in vitro specific cellular immunoresponse. Flow cytometry was used to measure the proliferation of CD3+/CD4+/CD8+ T and interferon [INF]-γ/interleukin [IL]-2/tumor necrosis factor [TNF]-α T cell subsets.Results: The BKV infection increased SCr values in recipients of renal transplantation. CD4+ T cells were dominant (>90%) in the in vitro cellular immunoresponse to VP1, VP2, VP3, LT-Ag, and st-Ag. At the presence of viremia and BKVN, IL-2/IFN-γ+/TNF-α+ CD4+ T cells showed significantly decreased in vitro cellular immunoresponse to VP1, VP2, and VP3 (p < 0.05), but insignificantly changed to LT-Ag and st-Ag (p > 0.05). For the cases of viruria and viremia, IL-2/IFN-γ+/TNF-α+ CD4+ T cells showed significantly higher in vitro cellular immunoresponse to VP1, VP2, and VP3 than to LT-Ag and st-Ag (p < 0.05). The immunogenicity of VP1 and VP3 was significantly higher than that of VP2 (p < 0.05).Conclusions: The BKV infection increases SCr values, and CD4+ T cells are dominant in the in vitro BKV specific cellular immunoresponse in the recipients of renal transplantation. Viremia significantly decreased the immunoresponse to VP1, VP2, and VP3. There is the significantly stronger immunoresponse to VP1 and VP3 when compared with that to VP2, LT-Ag, and st-Ag, suggesting that VP1 and VP3 may be the major targets for the BKV specific immune response. [ABSTRACT FROM AUTHOR]

Abstract Polyomavirus BK infection is a common complication and a major cause of morbidity after kidney transplantation. Surveillance of kidney transplant recipients was threatened by reactivation of polyomavirus BK infection can lead to polyomavirus BK-associated nephropathy (PVN). Antiviral immunoregulatory markers like Gamma interferon (IFN-γ) might also affect the polyomavirus BK pathogenesis for its role in antiviral host defense, graft rejection, and regulative of the adaptive immune responses. After screening polyomavirus BK infection, using Real time PCR (Taq-Man), the possible association between polyomavirus BK infection with IFN-γ gene expression was assessed. The mRNA levels of IFN-γ was examined in (n = 23) polyomavirus BK infected and (n = 23) non-infected kidney transplant patients in comparison with healthy controls (n = 23), using an in-house Real time PCR (SYBR Green) assay. The correlation of IFN-γ expression with viral load as well as other variables was also performed. The mRNA expression level of IFN-γ was significantly higher in polyomavirus BK infected patients (fold = 58.47) compared with non-infected ones (fold = 4.62), and healthy controls (p = 0.002). IFN-γ expression was higher in patients with higher viral load (p = 0.001). IFN-γ expression was correlated with viral load (r = 0.7, p < 0.0001). Accordingly, polyomavirus BK infection can induce IFN-γ gene over expression in kidney transplant infected patients. The results emphasized on the determinative role of IFN-γ in the pathogenesis of activated polyomavirus BK infection and also its importance in managing the clinical complications after kidney transplantation due to virus reactivation, requiring further investigation. Highlights • IFN-γ expression level was increased in kidney transplant patients with polyomavirus BK infection. • Higher polyomavirus BK DNA load was correlated with higher expression of IFN-γ. • IFN-γ expression might be a potential marker during follow up of polyomavirus BK infection. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: BK polyomavirus can lead to hemorrhagic cystitis (BKPyV‐HC) in allogeneic stem cell transplantation and therefore to increased morbidity. No causal therapy has been established yet. Cidofovir (CDV) is a nucleotide analog of cytosine that is active against various DNA viruses and it has been described for therapy of BKPyV‐HC using 2 admission routes: intravenous and intravesical. Methods: We performed a systematic review regarding the comparison of intravenous or intravesical cidofovir in the treatment of BKPyV‐HC following adult allogeneic stem cell transplantation. Since there is a lack of randomized controlled trials, we considered all kinds of studies for this review. Due to heterogeneity of the data, we were not able to perform a meta‐analysis, so the results are shown descriptively. Results: The literature search for primary studies yielded 232 results. Finally, 9 studies where considered which included a total of 189 adult patients with BKPyV‐HC after allogeneic stem cell transplantation. We could only identify retrospective studies for this review. A total of 172 patients received intravenous CDV, 17 patients received intravesical CDV, and 2 patients received CDV in both admission routes. In 68.0% of the cases, a complete response for intravenous CDV was documented and in 88.2% for intravesical CDV. Interestingly, no kidney toxicity was mentioned in intravesical CDV. 9.3% of the intravenously treated patients had renal failure. Conclusion: There is only weak evidence for the use of CDV. The intravesical admission route should be further investigated because of a good toxicity profile. [ABSTRACT FROM AUTHOR]

Background: Surveillance biopsies (SBs) are performed in some pediatric kidney transplant programs, based on data obtained in earlier immunosuppressive eras that the treatment of subclinical acute rejection results in better graft survival. The benefit of SBs for patients on modern immunosuppression regimens is unclear. We have therefore evaluated the clinical utility of SBs in a population of children receiving a kidney transplant.Methods: We have performed SBs at 3, 6 and 12 months post-transplantation as standard of care at our institution since 2013 in patients on a regimen of rabbit anti-thymocyte globulin, tacrolimus, mycophenolate and rapid steroid taper (RST; steroids maintained in some exceptions). We reviewed pathology reports of 82 SBs from 34 transplants in 34 children for all abnormal findings and adequacy of specimens. Clinical records were reviewed for changes in management resulting from SB findings and for significant procedure complications.Results: Of the 82 biopsies, 41 (50%) had abnormal findings separate from fibrosis, including five Banff Grade I rejections, ten borderline rejections, six calcineurin-inhibitor nephrotoxicity, four BK-virus nephropathy, five recurrent disease and three acute pyelonephritis. Moderate or more fibrosis was present in nine of the 82 (11%) biopsies. Management changes due to SB findings occurred in nine cases (11.0%). The proportion of abnormal findings or management changes did not differ between the RST or steroid-based groups. Patients performing clean intermittent catheterization showed inflammatory changes often read as rejection, but were managed differently. Three biopsies were deemed inadequate. No significant complications occurred.Conclusions: A high percentage of the SBs performed under modern immunosuppression showed abnormal findings even when fibrosis was excluded. However, management changes due to the SB findings were less frequent, although they occurred in a clinically meaningful percentage of cases. Complications or inadequate specimens were rare. [ABSTRACT FROM AUTHOR]

Background Studies have shown conflicting results on the prevalence and the risks of BK reactivation among pregnant women. In addition, the prevalence of vertical transmission and its clinical significance during pregnancy are not well studied. Objectives The study’s aims were (1) to investigate the prevalence, and (2) to assess the risk of BK Polyomavirus reactivation and its clinical significance in pregnant women and fetuses. Study design A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception through May 31, 2017. We included studies that reported prevalence, relative risks, odds ratios, or hazard ratios of BK Polyomavirus reactivation during pregnancy. Pooled odds ratios (ORs) and 95% CI were calculated using a random-effect model. The protocol for this study is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017063919). Results 17 observational studies with a total of 2553 pregnant women were enrolled. The estimated prevalence of BK seropositivity and BK in urine (viruria) among pregnant women were 79.2% (95%CI: 69.6%–86.4%) and 18.9% (95%CI: 10.4%–31.8%). When compared to non-pregnant women, the pooled ORs of BK seropositivity and BK viruria in pregnant women were 1.84 (95%CI: 1.05–3.22) and 6.02 (95%CI: 2.43–14.92), respectively. The estimated prevalence of positive BK-specific IgM antibody in cord blood was 4.9% (95%CI: 0.5%–36.2%). The data on the fetal effects of BK virus were limited. Although BK was detected in fetal organs, available data suggested no association between BK infection and adverse consequences such as miscarriage during pregnancy or childhood malignancy. Conclusion Our meta-analysis demonstrates a significantly increased risk of BK Polyomavirus reactivation during pregnancy. Although vertical transmission can occur with an overall estimated prevalence of 4.9%, there are currently no data suggesting harm to pregnant women and fetuses from BK Polyomavirus. [ABSTRACT FROM AUTHOR]

Purpose: BK virus (BKV) has a worldwide seroprevalence in humans. Based on sequences of the major capsid proteins, i.e. viral protein 1 (VP1), there are four BKV genotypes. Each genotype has its own subtypes, and was shown to be circulating independently in the human population. The aim of this study was to determine BKV genotypes and subtypes among Iranian patients with prostatic cancer, benign prostatic hyperplasia, and kidney transplantation. Materials and Methods: BKV DNA was extracted from prostatic cancers and benign prostatic hyperplasia blocks and also urine of kidney transplantation patients. BKV (VP1) gene was amplified partially (327nt) by homemade polymerase chain reactions and subjected for sequencing and phylogenetic analysis. Bioedit version 7.0 and Mega version 5.0 were used for sequence analysis and for comparing the results with world-driven BKV sequences. Results: All of BKV VP1 genes which were derived from Iranian patients were classified with subtype 1b2 strains from Germany and Turkey. Predicted amino acid sequences from the studied region of VP1 showed that all of these nucleotide diversities could change amino acid sequence numbers 60, 68, 72, 73 and 82 among VP1. Conclusion: The interesting point was that genetic analysis of derived sequences showed a different feature of genetic diversity among Iranian sequences. This feature has not been reported yet. This characteristic feature of Iranian BKV VP1 gene provides a unique cluster of sequences in phylogenetic tree. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Polyomavirus nephropathy ( PVN) is a major complication of kidney transplantation. Most reports describe polyomavirus viremia either precedes or is detectable at the time of diagnosis of PVN. This association is the basis of current screening recommendations. We retrospectively reviewed the PCR results of blood and urine samples from 29 kidney transplant recipients with biopsy-proven PVN. Biopsies were performed for a rise in serum creatinine or persistent high-level BK viruria. All biopsies showed polyoma virus large T-antigen expression in tubular epithelium using immunohistochemistry. All had viruria preceding or at the time of biopsy (range, 5.2 × 104 to >25 × 106 BKV DNA copies/ml). Twenty (69%) had viremia ranging from 2.5 × 103 to 4.3 × 106 copies/ml at the time of the biopsy. Via blood BK PCR assay, nine (31%) had no BK viremia detected either preceding or at the time of the biopsy. In five recipients where sufficient specimen permitted, additional plasma BK assessment revealed positive detection of viremia. A comparative analysis of assays from two centres was performed with spiked samples. BK DNA may not be detected in the blood of some kidney transplant recipients with histologically confirmed PVN. This may reflect limitation of whole blood as opposed to plasma-based BK DNA assessment. [ABSTRACT FROM AUTHOR]

BK virus (BKV) nephropathy has increasingly become an important cause of morbidity in renal transplant recipients. We evaluated the frequency and associated factors for BKV infection in a center performing mainly living donor transplantations over a long time period.~Purpose~Objective~One hundred consecutive renal transplant patients were included. Quarterly visits were planned to examine urine for decoy cells and to measure the BKV DNA in the blood and urine. Renal biopsy was performed in case of deteriorated allograft function. Serological examinations for BKV immunoglobulin G (IgG) were performed in donors.~Methods~Methods~Throughout the entire follow-up period, the rates of viruria, viremia, and the positivity of decoy cells were 12%, 6%, and 13%, respectively. The negative and positive predictive values of decoy cells were 93.1% and 69.2%, respectively, for viruria, and 99.2% and 45.5%, respectively, for viremia. Biopsy-proven BKV nephropathy was observed in 1 patient. The BKV IgG was positive in all living donors. Viruria and viremia were associated with deceased donor transplantation, acute rejection, and pulse steroid therapy. In addition, viremia was associated with antithymocyte globulin therapy and a short duration of the posttransplant period.~Results~Results~The frequency of BKV infection was lower in our transplant unit compared to previous reports. Reduced doses of immunosuppression seem to be the main factor that may explain the reduced frequency. However, an active screening strategy is still of importance for this patient group.~Conclusions~Conclusions [ABSTRACT FROM AUTHOR]

Background New clinical approaches to diagnose and monitor individuals with systemic diseases have been employed through the use of oral fluids. Polyomavirus BK (BKPyV) and JC (JCPyV) infect asymptomatically around 80% of general population worldwide remaining latent in the body. In case of immunosuppression, a replication can occur, leading to diseases. Objective The aim of this study was to detect and quantify BKPyV and JCPyV in oral fluids of individuals with chronic kidney failure (CKF), kidney transplantation (KT) and controls compared with their detection in blood and urine, traditionally used for this test. Study design Forty six subjects were included and distributed into 3 groups: 14 with CKF (Group 1), 12 with KT (Group 2) and 20 healthy individuals (Group 3). In a total, 315 samples were collected and analyzed through RT-PCR, being 151 of gingival crevicular fluid, 46 of saliva, 46 of mouthwash, 43 of blood and 29 of urine. Results All subjects from group 1 were positive for BKPyV in at least one collected samples and 14% were positive for JCPyV. In Group 2, 91.7% were positive for BKPyV and 51.7% for JCPyV. Among subjects of Group 3, 80% were positive for BKPyV and 45% for JCPyV. Conclusions Oral fluids exhibited high prevalence of BKPyV and JCPyV and were equally efficient compared to urine and blood. The use of oral fluids to detect these polyomaviruses enhances positivity in screening, even in cases of absence of viremia and especially in individuals who are not able to urinate. [ABSTRACT FROM AUTHOR]

Background BK polyomavirus ( BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant ( HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery. Methods We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BKPyV viruria. Results We identified a total of 2477 patients with a median age of 52 years. BKPyV viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BKPyV viruria development was 42 days among the patients who had BKPyV viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+, CD4+, CD8+, CD56+, NK counts, and low platelet count were shown to be significantly associated with BKPyV infection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings. Conclusion In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection. [ABSTRACT FROM AUTHOR]

To date, only one case of BK polyomavirus (BKPyV) encephalitis combined with transplant-associated thrombotic microangiopathy has been reported in an hematopoietic stem cell transplantation (HCT) recipient. We report the case of an HCT recipient who developed thrombotic microangiopathy and subsequent BKPyV encephalitis. She died despite treatment with cidofovir, ciprofloxacin, and intravenous immunoglobulin without improvement in mental status. Early suspicion of BKPyV encephalitis in an HCT recipient presenting with altered mental status and hemorrhagic cystitis is important. [ABSTRACT FROM AUTHOR]

For more than 40 years, polyomaviruses (BK virus and JC virus) have been known to cause disease in human beings. Recently, 11 new polyomaviruses were discovered. However, the majority of these viruses are rare in renal transplant recipients and BK and JC viruses remain the most important polyomaviruses to impact this population. BK virus presents as BK virus nephropathy and has, in rare instances, been associated with hemorrhagic cystitis or ureteral strictures. JC virus can cause progressive multifocal leukoencephalopathy or nephropathy in this population as well, but is uncommon. Antiviral prophylactic and therapeutic interventions for these diseases are lacking to date, although reduction of immunosuppression has been associated with success in treating both BK virus nephropathy and JC virus-induced disease. Risk factors are not well defined and vary across studies. However, the cumulative degree of immunosuppression is regarded universally as an important contributor to BK virus replication. For these reasons, it is recommended to screen all renal transplant recipients prospectively for BK virus infection. Multicenter trials using standardized BK and JC virus screening methods are necessary to define risk factors better, and to determine the effect of prophylaxis and treatments for these polyomaviruses affecting renal transplant recipients. [ABSTRACT FROM AUTHOR]

Background: BK virus is a polyoma virus causing renal allograft nephropathy. Reduction of immunosuppression with the early recognition of significant BK viral loads in urine and plasma can effectively prevent BKV associated nephropathy (BKVN), however the optimal compartment and frequency of BK viral load measurement post renal transplantation are undetermined. Our purpose was to examine time to detection and viral loads in urine compared to plasma, and establish viral load cut-offs associated with histological BKVN.Methods: We performed a retrospective analysis of the BKV screening frequency and compartment(s) of 277 adult renal transplant recipients (RTR).Results: BKVN was histologically diagnosed in 17 (6.1 %) RTR. In cases where both urine and plasma were tested fortnightly for 6 months (n = 53), BKV was detected in the urine 29 days earlier than plasma. Fortnightly (n = 72) versus 3-monthly (n = 78) testing demonstrated that BKV was detected in the urine significantly earlier (median 63 versus 97 days, p = 0.001) and at a lower level (median 3.27 versus 6.71 log10 c/mL, p < 0.001) with more frequent testing, but this difference was not evident in plasma first detection (80 versus 95 days, p = 0.536) or first positive viral load (3.18 versus 3.30 log10 c/mL, p = 0.603). The optimum cut-off BK viral load for histological diagnosis of BKVN was 4.10 log10 c/mL for the first positive urine, 3.79 log10 c/mL for the first positive plasma, 9.24 log10 c/mL for the peak urine, and 4.53 log10 c/mL for the peak plasma.Conclusions: Frequent urinary BK viral load screening for the prevention of BKVN is suggested due to its high sensitivity and earlier detection. [ABSTRACT FROM AUTHOR]

Objective: BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. Materials and Methods: From January 2005 to June 2014, among the 69 patients that underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Results: HC was observed in 30 patients (43.5%), and among them, 18 of the cases (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (minimum-maximum: 13-63). Patients received Allo-SCT for acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1). The donor types were human leukocyte antigen (HLA)-matched sibling donor for six patients, HLA-matched unrelated donor for nine, and haploidentical familial donor for two. The median onset and duration of BKV-HC was on day 21 after transplantation (minimum-maximum: 7-97) and 22 days (minimum-maximum: 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response, one had partial response, and five had no response. Among the five nonresponders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, achieving complete response (n=2) and partial response (n=2). The median duration from the start of leflunomide therapy to response was 13 days (minimum-maximum: 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. Conclusion: BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who do not respond to supportive care, leflunomide may be a feasible option without significant toxicity. [ABSTRACT FROM AUTHOR]

Background Little information is available on the risk factors for graft loss in kidney transplant recipients with BK polyomavirus ( BKPyV) nephropathy ( BKVN) in the presence or absence of antibody-mediated rejection ( AMR). Methods We examined the risk factors for graft loss in consecutive kidney allograft recipients with biopsy-confirmed BKVN, with or without concomitant AMR. Results A total of 1904 kidney transplants were performed at our institution during 2005-2011. Of these, 330 (17.33%) were diagnosed with BKPyV viremia, and 69 were diagnosed with BKVN (3.6%). Eleven patients had a concomitant diagnosis of AMR. Patients with AMR were characterized by significantly higher peak panel-reactive antibody, retransplant rates, and desensitization preconditioning at the time of transplantation, as well as microvascular inflammation ( MVI = glomerulitis + peritubular capillaritis), C4d score, and donor-specific antibody at the time of diagnosis ( P ≤ 0.01). Treatment with plasma exchange, intravenous immunoglobulin, and cidofovir was more prevalent in this group ( P ≤ 0.02). Univariate analyses assessing the risk factors for graft loss in all patients with BKVN, identified an independent association of African-American race, deceased-donor transplantation, serum creatinine (Scr), MVI, and early disease ( BKVN within 6 months of transplant) with poor outcomes. Multivariate analyses retained only 3 variables: Scr >2 mg/dL (hazard ratio [ HR] = 4.3, 95% confidence interval [ CI] 1.9-9.7, P = 0.0004), early BKVN ( HR = 2.7, 95% CI 1.3-5.3, P = 0.004), and MVI ( HR = 1.8, 95% CI 1.2-2.8, P = 0.008). Conclusions These observations suggest that, in patients with BK infection, early BKVN, Scr >2, and MVI are predictors of poor outcomes. Further studies are needed to determine effective treatment strategies for BKVN, with or without AMR. [ABSTRACT FROM AUTHOR]

Qualitative polymerase chain reaction (PCR) was used to determine the prevalence of fecal excretion of BK virus, JC virus, and simian virus 40 in 1-year-old infants. Overall, 17.8% of 321 specimens from 64.1% of 39 infants were polyomavirus positive. These data suggest that the gastrointestinal tract may be a site of polyomavirus persistence in humans. [ABSTRACT FROM AUTHOR]

Objective: To evaluate value of quantitative and qualitative detection of BK virus (BKV) and JC virus (JCV) in timely diagnosing polyomavirus-associated nephropathy (PVAN) occurring inrenal transplantation recipients. Methods: We collected 306 cases of urine specimen and 310 cases of blood specimen from 306 patients who underwent renal transplant. Levels of BKV and JCV in blood and urine were detected using real-time quantitative polymerase chain reaction (PCR). Results: Detection rate of BKV DNA was 33.3% (102/306) in urine and 34.8% (108/310); while that of JCV DNA was 30.7% (94/306) and 33.5% (104/310) respectively. The lowest detectable limit of BCK and JCV detection for patients who underwent renal transplant was 2×10³ copies/ml, suggesting high specificity and sensitivity. Conclusion: Real-time quantitative PCR is able to monitor BCV and JCV in renal transplant recipients in a convenient and rapid way, thus it is beneficial for early discovery, diagnosis and treatment of PVAN. [ABSTRACT FROM AUTHOR]

Purpose: Polyoma virus hominis 1, better known as BK virus (BKV) infection might be a predisposing factor for prostate cancer (PCa). The aim of this study was to compare the frequency of BK virus infection in pathological specimens of patients with PCa compared to patients with benign prostatic hyperplasia. Materials and Methods: From July 2011 to June 2012, paraffin-embedded tissue blocks of patients with PCa (60 specimens) and also with benign prostatic hyperplasia (60 specimens) were investigated. After DNA purification, existence of virus nucleic acid was assessed by polymerase chain reaction. Results: Viral DNA was identified in 9 patients (15%) with BPH and 17 patients (28%) with PCa (P =.076). In patients with PCa, viral DNA was observed more often in those with lower total Gleason scores (P = .045). Conclusion: The frequency of BK virus infection in PCa patients was higher than BPH patients. BK virus was more often observed in patients with lower Gleason scores. Less detection of BK virus DNA in overt cancer may prove the activity of the virus which paves the way for tumorigenic transformation at early stages of PCa. [ABSTRACT FROM AUTHOR]

Background: BK virus (BKV) is a common human polyomavirus which infects up to 90% of the general population with little clinical significance and with various epidemiological patterns of infection. Immune suppression is considered the main risk factor for BKV reactivation. Owing to their impaired cellular and humoral immunity, patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) are at high risk of infectious diseases such as BKV infection. BKV presents with different distributions in different populations. This study aimed to determine the prevalence of BKV in Iranian patients with chronic renal disease undergoing HD and PD. Methods: Sixty-three HD patients and 33 PD cases from the main dialysis units in Tehran, Iran, were enrolled in the study. BK viremia was determined by qualitative polymerase chain reaction in all subjects. Results: Sixty-three cases under HD (mean age 59.3 ± 14.5 years) and 33 subjects on PD (mean age 53.7 ± 13 years) were enrolled in the study. The mean duration of HD was 59.1 ± 53.8 months and the dialysis interval was three times a week. In the PD group, the mean duration of dialysis was 38.9 ± 35.2 months. The prevalence of BK viremia was 3.03% in PD and 0% in HD subjects. Conclusions: This study showed a low rate of BK viremia in chronic renal disease patients undergoing HD or PD. Differently from other studies in various populations, our results demonstrated low or absent BKV replication in Iranian dialysis patients, highlighting the varying epidemiological pattern of BKV distribution. [ABSTRACT FROM AUTHOR]

Polyomaviruses are non-enveloped, dsDNA viruses that are common in mammals, including humans. All polyomaviruses encode the large T-antigen and small t-antigen proteins that share conserved functional domains, comprising binding motifs for the tumor suppressors pRb and p53, and for protein phosphatase 2A, respectively. At present, 13 different human polyomaviruses are known, and for some of them their large T-antigen and small t-antigen have been shown to possess oncogenic properties in cell culture and animal models, while similar functions are assumed for the large T- and small t-antigen of other human polyomaviruses. However, so far the Merkel cell polyomavirus seems to be the only human polyomavirus associated with cancer. The large T- and small t-antigen exert their tumorigenic effects through classical hallmarks of cancer: inhibiting tumor suppressors, activating tumor promoters, preventing apoptosis, inducing angiogenesis and stimulating metastasis. This review elaborates on the putative roles of human polyomaviruses in some of the emerging hallmarks of cancer. The reciprocal interactions between human polyomaviruses and the immune system response are discussed, a plausible role of polyomavirus-encoded and polyomavirus-induced microRNA in cancer is described, and the effect of polyomaviruses on energy homeostasis and exosomes is explored. Therapeutic strategies against these emerging hallmarks of cancer are also suggested. [ABSTRACT FROM AUTHOR]

Background BK polyomavirus (BKV) infection and nephropathy complicate renal allografts; however, their effect in the native kidneys of pediatric heart transplant (HTx) recipients is unknown. We assessed the prevalence of BKV infection and its association with kidney dysfunction in survivors of pediatric HTx. Methods A single-center retrospective study compared pediatric (aged <18 years ) HTx recipients, with and without BKV (controls), who received an allograft from May 1989 to July 2013. Screening of urine for BKV was performed in patients with chronic kidney disease (CKD) stage ≥2 since 2006, and since April 2012 in all HTx recipients at least at an annual evaluation. Serum for BKV DNA was assayed if BK viruria was present. Data collected included recipient and donor demographics, the immunosuppressive regimen, and history of Epstein-Bar virus (EBV) and cytomegalovirus infection. Statistics included Fisher’s exact test, chi-square test, Student’s t -test, and multivariate logistic regression. Results Of 98 eligible recipients, 83 (85%) were screened: 28 (34%) had BK viruria, and 7 had BK viremia. One viremic patient had biopsy-proven BKV nephropathy that progressed to end-stage renal disease. Risk factors for BK viruria were (1) longer duration since HTx (6.02 vs 2.95 years; p = 0.01), (2) worsening estimated glomerular filtration rate (71.3 vs 86.3 ml/min/1.73 m 2 , p = 0.03), (3) history of EBV infection ( p = 0.0002), and (4) use of sirolimus ( p = 0.0003). After multivariate logistic-regression, only history of EBV infection remained associated with BKV infection ( p = 0.015). Conclusions BKV may lead to BK viremia and BK nephropathy in pediatric HTx patients. Routine screening for BK viruria should be considered. [ABSTRACT FROM AUTHOR]