51 results on '"Polyomavirus Infections diagnosis"'
Search Results
2. The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation.
- Author
-
Kotton CN, Kamar N, Wojciechowski D, Eder M, Hopfer H, Randhawa P, Sester M, Comoli P, Tedesco Silva H, Knoll G, Brennan DC, Trofe-Clark J, Pape L, Axelrod D, Kiberd B, Wong G, and Hirsch HH
- Subjects
- Humans, Risk Factors, Antiviral Agents therapeutic use, Treatment Outcome, Kidney Transplantation adverse effects, BK Virus immunology, BK Virus pathogenicity, Polyomavirus Infections diagnosis, Polyomavirus Infections immunology, Polyomavirus Infections virology, Consensus, Tumor Virus Infections immunology, Tumor Virus Infections diagnosis, Tumor Virus Infections virology, Immunosuppressive Agents therapeutic use, Immunosuppressive Agents adverse effects
- Abstract
BK polyomavirus (BKPyV) remains a significant challenge after kidney transplantation. International experts reviewed current evidence and updated recommendations according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Risk factors for BKPyV-DNAemia and biopsy-proven BKPyV-nephropathy include recipient older age, male sex, donor BKPyV-viruria, BKPyV-seropositive donor/-seronegative recipient, tacrolimus, acute rejection, and higher steroid exposure. To facilitate early intervention with limited allograft damage, all kidney transplant recipients should be screened monthly for plasma BKPyV-DNAemia loads until month 9, then every 3 mo until 2 y posttransplant (3 y for children). In resource-limited settings, urine cytology screening at similar time points can exclude BKPyV-nephropathy, and testing for plasma BKPyV-DNAemia when decoy cells are detectable. For patients with BKPyV-DNAemia loads persisting >1000 copies/mL, or exceeding 10 000 copies/mL (or equivalent), or with biopsy-proven BKPyV-nephropathy, immunosuppression should be reduced according to predefined steps targeting antiproliferative drugs, calcineurin inhibitors, or both. In adults without graft dysfunction, kidney allograft biopsy is not required unless the immunological risk is high. For children with persisting BKPyV-DNAemia, allograft biopsy may be considered even without graft dysfunction. Allograft biopsies should be interpreted in the context of all clinical and laboratory findings, including plasma BKPyV-DNAemia. Immunohistochemistry is preferred for diagnosing biopsy-proven BKPyV-nephropathy. Routine screening using the proposed strategies is cost-effective, improves clinical outcomes and quality of life. Kidney retransplantation subsequent to BKPyV-nephropathy is feasible in otherwise eligible recipients if BKPyV-DNAemia is undetectable; routine graft nephrectomy is not recommended. Current studies do not support the usage of leflunomide, cidofovir, quinolones, or IVIGs. Patients considered for experimental treatments (antivirals, vaccines, neutralizing antibodies, and adoptive T cells) should be enrolled in clinical trials., Competing Interests: C.N.K. received grants from Biohope and funding for serving on scientific advisory boards for Roche Diagnostics. N.K. received consulting fees, honoraria, and travel support from Astellas, AstraZeneca, Biotest, CSL Behring, Chiesi, Gilead, Hansa, Merck, Sharp and Dohme, Glasgow Smith Kline, Neovii, Novartis Pharma, Roche, Sanofi, Sandoz, and Takeda. P.R. received consulting fees from Allovir. M.S. received consulting fees from Merck, Sharp and Dohme, Moderna, and Biotest and honoraria from Biotest, Novartis, Merck, Sharp and Dohme, Takeda, and Qiagen. P.C. received honoraria from Atara Bio and Pierre Fabre Pharma. H.T.S. received grants from Biohope, Merck Sharp and Dohme, Natera, Novartis, and Takeda; honoraria from Alexion, CareDx, EMS Pharmaceuticals, Natera, and Takeda; and consulting fees and travel support from Takeda. D.C.B. received grants from CareDx and VeraTherapeutics and consulting fees from CareDx, Medeor Therapeutics, Natera, Sanofi, and Vera Therapeutics. L.P. received grants from Alexion, Chiesi, and Novartis; consulting fees from Alnylam and Chiesi; and travel support from Alexion. H.H.H. received consulting fees from AICuris, Allovir, Moderna, VeraTX, and Roche and honoraria from VeraTX, Takeda, Biotest, and Gilead. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
- Full Text
- View/download PDF
3. Concurrent JCPyV-DNAemia Is Correlated With Poor Graft Outcome in Kidney Transplant Recipients With Polyomavirus-associated Nephropathy.
- Author
-
Zhang H, Luo JQ, Zhao GD, Huang Y, Yang SC, Chen PS, Li J, Wu CL, Qiu J, Chen XT, and Huang G
- Subjects
- Humans, Female, Male, Middle Aged, Adult, Retrospective Studies, BK Virus pathogenicity, Risk Factors, Kidney Diseases surgery, Kidney Diseases virology, Kidney Diseases mortality, Kidney Diseases diagnosis, Tumor Virus Infections virology, Tumor Virus Infections diagnosis, Tumor Virus Infections mortality, Treatment Outcome, Coinfection, Nomograms, Graft Rejection virology, Aged, Kidney Transplantation adverse effects, Kidney Transplantation mortality, Polyomavirus Infections virology, Polyomavirus Infections diagnosis, Graft Survival, DNA, Viral blood
- Abstract
Background: Co-infection of JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) is uncommon in kidney transplant recipients, and the prognosis is unclear. This study aimed to investigate the effect of concurrent JCPyV-DNAemia on graft outcomes in BKPyV-infected kidney transplant recipients with polyomavirus-associated nephropathy (PyVAN)., Methods: A total of 140 kidney transplant recipients with BKPyV replication and PyVAN, 122 without concurrent JCPyV-DNAemia and 18 with JCPyV-DNAemia were included in the analysis. Least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to identify prognostic factors for graft survival. A nomogram for predicting graft survival was created and evaluated., Results: The median tubulitis score in the JCPyV-DNAemia-positive group was higher than in JCPyV-DNAemia-negative group ( P = 0.048). At last follow-up, the graft loss rate in the JCPyV-DNAemia-positive group was higher than in the JCPyV-DNAemia-negative group (50% versus 25.4%; P = 0.031). Kaplan-Meier analysis showed that the graft survival rate in the JCPyV-DNAemia-positive group was lower than in the JCPyV-DNAemia-negative group ( P = 0.003). Least absolute shrinkage and selection operator regression and multivariate Cox regression analysis demonstrated that concurrent JCPyV-DNAemia was an independent risk factor for graft survival (hazard ratio = 4.808; 95% confidence interval: 2.096-11.03; P < 0.001). The nomogram displayed favorable discrimination (C-index = 0.839), concordance, and clinical applicability in predicting graft survival., Conclusions: Concurrent JCPyV-DNAemia is associated with a worse graft outcome in BKPyV-infected kidney transplant recipients with PyVAN., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
- Full Text
- View/download PDF
4. Urine CXCL10 to Assess BK Polyomavirus Replication After Kidney Transplantation.
- Author
-
Haller J, Diebold M, Leuzinger K, Wehmeier C, Handschin J, Amico P, Hirt-Minkowski P, Steiger J, Dickenmann M, Hirsch HH, and Schaub S
- Subjects
- Humans, Biomarkers, Chemokine CXCL10 urine, Urine, BK Virus, Kidney Diseases, Kidney Transplantation adverse effects, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis
- Abstract
Background: Urine CXCL10 is a biomarker for renal allograft inflammation induced by rejection, urinary tract infection, or BK polyomavirus (BKPyV) replication. This study aimed to compare urine CXCL10 levels in different stages of BKPyV reactivation and to investigate urine CXCL10 as a biomarker for BKPyV replication., Methods: We included 763 urine samples (235 patients) from an interventional, randomized trial obtained in the context of regular screening for urine CXCL10 levels. All urine samples had a complete urine sediment analysis, no rejection episode noted within 30 d before urine collection, and a urine decoy cell analysis was conducted within ±3 d., Results: Urine CXCL10 levels were 2.31 ng/mmol in samples without BKPyV viruria, slightly rose to 4.35 ng/mmol with BKPyV viruria, and then markedly increased to 16.42 ng/mmol when decoy cells were detectable, but still in the absence of BKPyV DNAemia ( P < 0.001). The highest urine CXCL10 values were observed in samples with BKPyV DNAemia (median 42.59 ng/mmol). The area under the curve of urine CXCL10 levels to detect ≥3 decoy cells was 0.816. At a CXCL10 cutoff of 3 ng/mmol, the negative predictive value was 97%. The area under the curve of urine CXCL10 levels to detect BKPyV DNAemia was 0.882, with a negative predictive value of 99% at a CXCL10 cutoff of 3 ng/mmol., Conclusions: Urine CXCL10 levels are already significantly elevated in BKPyV viruria (especially with decoy cell shedding) and further increase with BKPyV DNAemia. Low urine CXCL10 values can rule out the presence of ≥3 decoy cells and BKPyV DNAemia with high certainty., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2023
- Full Text
- View/download PDF
5. Polyoma BK Virus in Kidney Transplant Recipients: Screening, Monitoring, and Management.
- Author
-
Myint TM, Chong CHY, Wyld M, Nankivell B, Kable K, and Wong G
- Subjects
- Humans, Transplant Recipients, BK Virus, Kidney Transplantation adverse effects, Polyomavirus, Polyomavirus Infections diagnosis, Polyomavirus Infections drug therapy, Polyomavirus Infections epidemiology, Tumor Virus Infections diagnosis, Tumor Virus Infections drug therapy, Tumor Virus Infections epidemiology
- Abstract
Polyomavirus BK virus (BKPyV) infection is an important complication of kidney transplantation and allograft failure. The prevalence of viremia is 10%-15%, compared with BK-associated nephropathy (BKPyVAN) at 3%-5%. Given that there are no effective antiviral prophylaxis or treatment strategies for BKPyVAN, active screening to detect BKPyV viremia is recommended, particularly during the early posttransplant period. Immunosuppression reduction to allow viral clearance may avoid progression to severe and irreversible allograft damage. The frequency and duration of screening are highly variable between transplant centers because the evidence is reliant largely on observational data. While the primary treatment goals center on achieving viral clearance through immunosuppression reduction, prevention of subsequent acute rejection, premature graft loss, and return to dialysis remain as major challenges. Treatment strategies for BKPyV infection should be individualized to the recipient's underlying immunological risk and severity of the allograft infection. Efficacy data for adjuvant therapies including intravenous immunoglobulin and cidofovir are sparse. Future well-powered and high-quality randomized controlled trials are needed to inform evidence-based clinical practice for the management of BKPy infection., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
6. The Use of Molecular Techniques to Distinguish BK Nephropathy From Acute Rejection: Close but not Quite.
- Author
-
Pesavento TE
- Subjects
- Humans, BK Virus genetics, Kidney Diseases, Polyomavirus Infections diagnosis
- Abstract
Competing Interests: The author declares no conflicts of interest.
- Published
- 2021
- Full Text
- View/download PDF
7. Clinicopathologic Characteristics of JC Virus Nephropathy in Kidney Transplant Recipients.
- Author
-
Wiegley N, Walavalkar V, Aujla H, Chen LX, Huang Y, Lee BK, and Jen KY
- Subjects
- Adult, Aged, Biopsy, California, Female, Fibrosis, Host-Pathogen Interactions, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, JC Virus immunology, Kidney immunology, Kidney pathology, Kidney Diseases diagnosis, Kidney Diseases immunology, Male, Middle Aged, Polyomavirus Infections diagnosis, Polyomavirus Infections immunology, Time Factors, Treatment Outcome, Tumor Virus Infections diagnosis, Tumor Virus Infections immunology, Viral Load, JC Virus pathogenicity, Kidney virology, Kidney Diseases virology, Kidney Transplantation adverse effects, Polyomavirus Infections virology, Tumor Virus Infections virology, Virus Activation
- Abstract
Background: The vast majority of polyomavirus nephropathy (PVN) is due to BK virus, but rare cases result from JC virus reactivation. To date, only a handful of biopsy-proven JC-PVN cases have been reported. Here, we describe the clinical and pathologic findings in 7 patients with biopsy-proven JC-PVN., Methods: Search of the pathology archives at 2 institutions found 7 cases of JC-PVN. Clinical data were extracted from the electronic medical records, and the biopsies were reviewed., Results: Four cases were diagnosed at 6 y posttransplant or later. The remaining 3 cases presented within approximately 2 y posttransplant, of which 2 showed subclinical JC-PVN on surveillance biopsy. Two early presenting patients were treated for acute rejection just before acquiring JC-PVN. Late presenting patients had higher chronicity, which correlated to worse outcome. All but 1 biopsy showed nonspecific inflammation within areas of interstitial fibrosis without significant inflammation in unscarred cortex. The earliest presenting patient was the exception and showed active inflammation with tubulitis. Viral cytopathic changes were detected in all cases with moderate or high-histologic viral load (pvl), showing preference for the distal tubules and medulla. The 2 cases with low pvl did not demonstrate cytopathic changes but were SV40 positive., Conclusions: JC-PVN can be insidious in presentation, which may cause delayed or missed diagnosis. Unlike BK-PVN, which typically occurs early in the posttransplant period, JC-PVN can occur both early and late following transplant. Overreliance on negative plasma and urine BK viral loads to exclude PVN can be a pitfall., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
8. BK Polyomavirus-specific T Cells as a Diagnostic and Prognostic Marker for BK Polyomavirus Infections After Pediatric Kidney Transplantation.
- Author
-
Ahlenstiel-Grunow T, Sester M, Sester U, Hirsch HH, and Pape L
- Subjects
- Adolescent, Age Factors, BK Virus growth & development, Cell Separation, Child, Child, Preschool, Disease Progression, Female, Flow Cytometry, Host-Pathogen Interactions, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Infant, Infant, Newborn, Lymphocyte Count, Male, Opportunistic Infections diagnosis, Opportunistic Infections virology, Polyomavirus Infections diagnosis, Polyomavirus Infections virology, Predictive Value of Tests, Prospective Studies, T-Lymphocytes virology, Time Factors, Treatment Outcome, Tumor Virus Infections diagnosis, Tumor Virus Infections virology, Virus Replication, BK Virus immunology, Kidney Transplantation adverse effects, Opportunistic Infections immunology, Polyomavirus Infections immunology, T-Lymphocytes immunology, Tumor Virus Infections immunology
- Abstract
Background: After kidney transplantation, uncontrolled BK polyomavirus (BKPyV) replication causes kidney graft failure through BKPyV-associated nephropathy (BKPyVAN), but markers predicting outcome are missing. BKPyV-specific T cells may serve as a predictive marker to identify patients at risk of persistent DNAemia and BKPyVAN., Methods: Out of a total of 114 pediatric kidney recipients transplanted between 2008 and 2018, 36 children with posttransplant BKPyV-DNAemia were identified. In a prospective noninterventional study, BKPyV-specific CD4 and CD8 T cells were measured in 32 of 36 viremic pediatric kidney recipients using intracellular cytokine staining and flow cytometry. The course of the BKPyV replication was monitored with regard to duration of BKPyV-DNAemia and need of therapeutic intervention and diagnosis of proven BKPyVAN., Results: Levels of BKPyV-specific T cells negatively correlated with subsequent duration of BKPyV-DNAemia. Patients with BKPyV-specific CD4 T cells ≥0.5 cells/µL and/or BKPyV-specific CD8 T cells ≥0.1 cells/µL had transient, self-limiting DNAemia (PPV 1.0, NPV 0.86). BKPyV-specific CD4 and CD8 T cells below these thresholds were found in children with persistent BKPyV-DNAemia and biopsy-proven BKPyVAN with need for therapeutic intervention. After reducing immunosuppressive therapy, levels of BKPyV-specific CD4 T cells increased while plasma BKPyV-DNAemia declined., Conclusions: This study found that BKPyV-specific T cell levels may help to distinguish patients with transient, self-limiting BKPyV-DNAemia from those with persisting BKPyV-DNAemia and biopsy-proven BKPyVAN, who would benefit from individualized therapeutic interventions such as reduced immunosuppression. Thereby the risk for rejection because of unnecessary reduction of immunosuppression in case of self-limiting BKPyV-DNAemia can be minimized.
- Published
- 2020
- Full Text
- View/download PDF
9. Differential Diagnosis of Interstitial Allograft Rejection and BKV Nephropathy by T-cell Receptor Sequencing.
- Author
-
Stervbo U, Nienen M, Hecht J, Viebahn R, Amann K, Westhoff TH, and Babel N
- Subjects
- BK Virus immunology, Diagnosis, Differential, Graft Rejection genetics, Graft Rejection immunology, Graft Rejection prevention & control, High-Throughput Nucleotide Sequencing, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Male, Opportunistic Infections genetics, Opportunistic Infections immunology, Opportunistic Infections virology, Polyomavirus Infections genetics, Polyomavirus Infections immunology, Polyomavirus Infections virology, Predictive Value of Tests, Treatment Outcome, Tumor Virus Infections genetics, Tumor Virus Infections immunology, Tumor Virus Infections virology, Viral Load, Young Adult, BK Virus pathogenicity, Genes, T-Cell Receptor, Graft Rejection diagnosis, Kidney Transplantation adverse effects, Opportunistic Infections diagnosis, Polyomavirus Infections diagnosis, Sequence Analysis, DNA, Tumor Virus Infections diagnosis
- Published
- 2020
- Full Text
- View/download PDF
10. BK Nephropathy as a Cause of Renal Dysfunction in an ABO-incompatible Liver Transplant Patient.
- Author
-
Lai C, Bleasel J, McGrath J, Majumdar A, Kirwan P, Anderson L, Strasser S, and Gracey D
- Subjects
- ABO Blood-Group System, Biopsy, Humans, Kidney pathology, Kidney virology, Kidney Diseases blood, Kidney Diseases pathology, Kidney Diseases virology, Liver Transplantation methods, Male, Middle Aged, Polyomavirus Infections blood, Polyomavirus Infections pathology, Polyomavirus Infections virology, Tumor Virus Infections blood, Tumor Virus Infections pathology, Tumor Virus Infections virology, BK Virus isolation & purification, Kidney Diseases diagnosis, Liver Transplantation adverse effects, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis
- Published
- 2020
- Full Text
- View/download PDF
11. Trichodysplasia Spinulosa.
- Author
-
Rosenstein RK, Ko CJ, and Colegio OR
- Subjects
- Antiviral Agents therapeutic use, Biopsy, Female, Hair Diseases diagnosis, Hair Diseases drug therapy, Hair Diseases immunology, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Middle Aged, Polyomavirus Infections diagnosis, Polyomavirus Infections drug therapy, Polyomavirus Infections immunology, Treatment Outcome, Hair Diseases virology, Kidney Transplantation adverse effects, Polyomavirus Infections virology
- Published
- 2017
- Full Text
- View/download PDF
12. Bladder Rupture After Chronic Hemorrhagic Cystitis in a Stem Cell Transplantation Recipient.
- Author
-
Imataki O, Uchida S, Kushida Y, and Uemura M
- Subjects
- BK Virus pathogenicity, Cystitis diagnosis, Cystitis therapy, Cystitis virology, Female, Hematuria etiology, Hemorrhage diagnosis, Hemorrhage therapy, Hemorrhage virology, Humans, Middle Aged, Polyomavirus Infections diagnosis, Polyomavirus Infections therapy, Rupture, Spontaneous, Tumor Virus Infections diagnosis, Tumor Virus Infections therapy, Urinary Bladder Diseases diagnosis, Urinary Bladder Diseases therapy, Urinary Bladder Diseases virology, Virus Activation, Cystitis etiology, Hemorrhage etiology, Polyomavirus Infections virology, Stem Cell Transplantation adverse effects, Tumor Virus Infections virology, Urinary Bladder Diseases etiology
- Published
- 2017
- Full Text
- View/download PDF
13. A Difficult Decision: Atypical JC Polyomavirus Encephalopathy in a Kidney Transplant Recipient.
- Author
-
Bialasiewicz S, Hart G, Oliver K, Agnihotri SP, Koralnik IJ, Viscidi R, Nissen MD, Sloots TP, Burke MT, Isbel NM, and Burke J
- Subjects
- Adult, Antibodies, Viral blood, Biopsy, Cerebral Angiography methods, Drug Administration Schedule, Humans, Immunocompromised Host, Immunohistochemistry, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents adverse effects, JC Virus genetics, JC Virus immunology, Kidney surgery, Leukoencephalopathy, Progressive Multifocal diagnosis, Leukoencephalopathy, Progressive Multifocal immunology, Leukoencephalopathy, Progressive Multifocal therapy, Magnetic Resonance Angiography, Male, Nephrectomy, Phlebography methods, Polyomavirus Infections diagnosis, Polyomavirus Infections immunology, Polyomavirus Infections therapy, Reoperation, Treatment Outcome, Viral Load, JC Virus isolation & purification, Kidney virology, Kidney Transplantation adverse effects, Leukoencephalopathy, Progressive Multifocal virology, Polyomavirus Infections virology
- Abstract
Background: A number of cerebral manifestations are associated with JC polyomavirus (JCPyV) which are diagnosed by detection of JCPyV in cerebrospinal fluid (CSF), often with the support of cerebral imaging. Here we present an unusual case of a kidney transplant patient presenting with progressive neurological deterioration attributed to JCPyV encephalopathy., Methods: Quantitative polymerase chain reaction JCPyV was used prospectively and retrospectively to track the viral load within the patient blood, urine, CSF, and kidney sections. A JCPyV VP1 enzyme-linked immunosorbent assay was used to measure patient and donor antibody titers. Immunohistochemical staining was used to identify active JCPyV infection within the kidney allograft., Results: JC polyomavirus was detected in the CSF at the time of presentation. JC polyomavirus was not detected in pretransplant serum, however viral loads increased with time, peaking during the height of the neurological symptoms (1.5E copies/mL). No parenchymal brain lesions were evident on imaging, but transient cerebral venous sinus thrombosis was present. Progressive decline in neurological function necessitated immunotherapy cessation and allograft removal, which led to decreasing serum viral loads and resolution of neurological symptoms. JC polyomavirus was detected within the graft's collecting duct cells using quantitative polymerase chain reaction and immunohistochemical staining. The patient was JCPyV naive pretransplant, but showed high antibody titers during the neurological symptoms, with the IgM decrease paralleling the viral load after graft removal., Conclusions: We report a case of atypical JCPyV encephalopathy associated with cerebral venous sinus thrombosis and disseminated primary JCPyV infection originating from the kidney allograft. Clinical improvement followed removal of the allograft and cessation of immunosuppression.
- Published
- 2017
- Full Text
- View/download PDF
14. Correlation of BK Virus Neutralizing Serostatus With the Incidence of BK Viremia in Kidney Transplant Recipients.
- Author
-
Abend JR, Changala M, Sathe A, Casey F, Kistler A, Chandran S, Howard A, and Wojciechowski D
- Subjects
- Adult, Aged, Biomarkers blood, Chi-Square Distribution, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Incidence, Logistic Models, Male, Middle Aged, Neutralization Tests, Odds Ratio, Opportunistic Infections diagnosis, Opportunistic Infections epidemiology, Opportunistic Infections virology, Polyomavirus Infections diagnosis, Polyomavirus Infections epidemiology, Polyomavirus Infections virology, Retrospective Studies, Risk Factors, San Francisco epidemiology, Time Factors, Treatment Outcome, Tumor Virus Infections diagnosis, Tumor Virus Infections epidemiology, Tumor Virus Infections virology, Antibodies, Neutralizing blood, Antibodies, Viral blood, BK Virus immunology, Kidney Transplantation adverse effects, Opportunistic Infections immunology, Polyomavirus Infections immunology, Tumor Virus Infections immunology
- Abstract
Background: BK virus (BKV)-associated nephropathy is the second leading cause of graft loss in kidney transplant recipients. Due to the high prevalence of persistent infection with BKV in the general population, it is possible that either the transplant recipient or donor may act as the source of virus resulting in viruria and viremia. Although several studies suggest a correlation between donor-recipient serostatus and the development of BK viremia, specific risk factors for BKV-related complications in the transplant setting remain to be established., Methods: We retrospectively determined the pretransplant BKV neutralizing serostatus of 116 donors (D)-recipient (R) pairs using infectious BKV neutralization assays with representatives from the 4 major viral serotypes. The neutralizing serostatus of donors and recipients was then correlated with the incidence of BK viremia during the first year posttransplantation., Results: There were no significant differences in baseline demographics or transplant data among the 4 neutralizing serostatus groups, with the exception of calculated panel-reactive antibody which was lowest in the D+/R- group. Recipients of kidneys from donors with significant serum neutralizing activity (D+) had elevated risk for BK viremia, regardless of recipient serostatus (D+ versus D-: odd ratio, 5.0; 95% confidence interval, 1.9-12.7]; P = 0.0008). Furthermore, donor-recipient pairs with D+/R- neutralizing serostatus had the greatest risk for BK viremia (odds ratio, 4.9; 95% confidence interval, 1.7-14.6; P = 0.004)., Conclusions: Donor neutralizing serostatus correlates significantly with incidence of posttransplant BK viremia. Determination of donor-recipient neutralizing serostatus may be useful in assessing the risk of BKV infection in kidney transplant recipients.
- Published
- 2017
- Full Text
- View/download PDF
15. Polyomavirus Replication and Smoking Are Independent Risk Factors for Bladder Cancer After Renal Transplantation.
- Author
-
Liu S, Chaudhry MR, Berrebi AA, Papadimitriou JC, Drachenberg CB, Haririan A, and Alexiev BA
- Subjects
- Academic Medical Centers, Adult, Female, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Incidence, Male, Maryland epidemiology, Middle Aged, Opportunistic Infections diagnosis, Opportunistic Infections epidemiology, Opportunistic Infections immunology, Polyomavirus immunology, Polyomavirus Infections diagnosis, Polyomavirus Infections epidemiology, Polyomavirus Infections immunology, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, Urinary Bladder Neoplasms diagnosis, Urinary Bladder Neoplasms epidemiology, Urinary Bladder Neoplasms immunology, Kidney Transplantation adverse effects, Opportunistic Infections virology, Polyomavirus growth & development, Polyomavirus Infections virology, Smoking adverse effects, Urinary Bladder Neoplasms virology, Virus Replication
- Abstract
Background: Solid organ transplant recipients are at increased risk for developing malignancies. Polyomaviruses (PV) have been historically associated with experimental tumor development and recently described in association with renourinary malignancies in transplant patients. The aim of this study was to investigate the relationship between PV replication and smoking, and the development of malignant neoplasms in kidney transplant recipients., Methods: A retrospective case-control study was conducted for PV replication in all kidney biopsies and urine cytologies performed between 1998 and 2014 from kidney transplant recipients at the University of Maryland Medical Center. Polyomavirus-positive patients (n = 943) were defined as having any of the following: a kidney biopsy with PV associated nephropathy, any urine cytology demonstrating "decoy" cells, and/or significant polyomavirus BK viremia. Polyomavirus-negative matched patients (n = 943) were defined as lacking any evidence of PV replication. The incidence of malignancy (excluding nonmelanoma skin tumors) was determined in these 1886 patients and correlated with demographic data and history of smoking., Results: There was a 7.9% incidence of malignant tumors after a mean posttransplant follow-up of 7.9 ± 5.4 years. Among all cancer subtypes, only bladder carcinoma was significantly associated with PV replication. By multivariate analysis, only PV replication and smoking independently increased the risk of bladder cancer, relative risk, 11.7 (P = 0.0013) and 5.6 (P = 0.0053), respectively., Conclusions: The findings in the current study indicate that kidney transplant recipients with PV replication and smoking are at particular risk to develop bladder carcinomas and support the need for long-term cancer surveillance in these patients.
- Published
- 2017
- Full Text
- View/download PDF
16. Increased Frequency of BK Virus-Specific Polyfunctional CD8+ T Cells Predict Successful Control of BK Viremia After Kidney Transplantation.
- Author
-
Schaenman JM, Korin Y, Sidwell T, Kandarian F, Harre N, Gjertson D, Lum EL, Reddy U, Huang E, Pham PT, Bunnapradist S, Danovitch GM, Veale J, Gritsch HA, and Reed EF
- Subjects
- Adult, Aged, Antiviral Agents therapeutic use, BK Virus drug effects, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes virology, Cytokines immunology, Female, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Male, Middle Aged, Opportunistic Infections diagnosis, Opportunistic Infections drug therapy, Opportunistic Infections virology, Phenotype, Polyomavirus Infections diagnosis, Polyomavirus Infections drug therapy, Polyomavirus Infections virology, Predictive Value of Tests, Risk Factors, Time Factors, Treatment Outcome, Tumor Virus Infections diagnosis, Tumor Virus Infections drug therapy, Tumor Virus Infections virology, Viremia immunology, Viremia virology, BK Virus immunology, CD8-Positive T-Lymphocytes immunology, Kidney Transplantation adverse effects, Opportunistic Infections immunology, Polyomavirus Infections immunology, Tumor Virus Infections immunology
- Abstract
Background: BK virus infection remains an important cause of loss of allograft function after kidney transplantation. We sought to determine whether polyfunctional T cells secreting multiple cytokines simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control., Methods: Peripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T-cell activation, exhaustion, and maturation., Results: BK virus controllers, defined as those with episodes of BK viremia of 3 months or less, had an 11-fold increase in frequency of CD8+ polyfunctional T cells expressing multiple cytokines, as compared with patients with prolonged episodes of BK viremia. Patients with only low level BK viremia expressed low frequencies of polyfunctional T cells. Polyfunctional T cells were predominantly of the effector memory maturation subtype and expressed the cytotoxicity marker CD107a., Conclusions: Noninvasive techniques for immune assessment of peripheral blood can provide insight into the mechanism of control of BK virus replication and may allow for future patient risk stratification and customization of immune suppression at the onset of BK viremia.
- Published
- 2017
- Full Text
- View/download PDF
17. The Noninvasive Urinary Polyomavirus Haufen Test Predicts BK Virus Nephropathy in Children After Hematopoietic Cell Transplantation: A Pilot Study.
- Author
-
Laskin BL, Singh HK, Beier UH, Moatz T, Furth SL, Bunin N, Witte D, Goebel J, Davies SM, Dandoy C, Jodele S, and Nickeleit V
- Subjects
- Adolescent, Adult, Case-Control Studies, Child, Female, Humans, Male, Pilot Projects, BK Virus isolation & purification, Hematopoietic Stem Cell Transplantation adverse effects, Kidney Diseases diagnosis, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis, Virus Shedding
- Abstract
Background: After hematopoietic cell transplantation (HCT), polyoma-BK virus is associated with hemorrhagic cystitis and also with polyomavirus nephropathy (PVN). However, the true burden of post-HCT PVN is unknown because kidney biopsies are avoided due to their bleeding risk. The novel, noninvasive urinary PV-Haufen test detects PVN in kidney transplant recipients with greater than 95% positive/negative predictive values. We hypothesized that the detection of PV-Haufen in voided urine samples-a positive PV-Haufen test-was also clinically significant after HCT., Methods: We examined 21 suitable urine samples from 14 patients (median age, 15 years; 71.4% male) who were selected from repositories for having varying degrees of BK viremia (range, 0-1.0 × 10 copies/mL), hemorrhagic cystitis (present/absent), and data on kidney function. Urine samples were obtained at a median of 88 days post-HCT., Results: The PV-Haufen were detected in 5 of 14 patients (35.7%) and 7 of 21 (33.3%) urine samples, with histologic confirmation of PVN in 1 autopsy specimen. After a median of 285 days post-HCT, patients with PV-Haufen had an increased risk of dialysis-dependent renal failure (P < 0.05). All 3 dialysis-dependent patients had PV-Haufen and died. The presence of urinary PV-Haufen was not significantly correlated with hemorrhagic cystitis. From the 16 urines collected during BK viremia, 43.8% were PV-Haufen-positive, and 56.2% were negative. The PV-Haufen were not present in the 5 urines from patients without concomitant BK-viremia., Conclusions: In this proof-of-concept study, a positive PV-Haufen test was only seen in some patients with BK viremia and was not associated with hemorrhagic cystitis. The detection of PV-Haufen suggests underlying PVN with an increased risk of kidney failure and dialysis.
- Published
- 2016
- Full Text
- View/download PDF
18. Viral Origin, Clinical Course, and Renal Outcomes in Patients With BK Virus Infection After Living-Donor Renal Transplantation.
- Author
-
Schwarz A, Linnenweber-Held S, Heim A, Framke T, Haller H, and Schmitt C
- Subjects
- Adult, Aged, BK Virus genetics, Biomarkers blood, Biomarkers urine, DNA, Viral blood, DNA, Viral genetics, DNA, Viral urine, Female, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Kidney Diseases diagnosis, Kidney Diseases immunology, Male, Middle Aged, Odds Ratio, Opportunistic Infections diagnosis, Opportunistic Infections immunology, Opportunistic Infections transmission, Polyomavirus Infections diagnosis, Polyomavirus Infections immunology, Polyomavirus Infections transmission, Prospective Studies, Risk Factors, Time Factors, Treatment Outcome, Tumor Virus Infections diagnosis, Tumor Virus Infections immunology, Tumor Virus Infections transmission, Viral Load, BK Virus pathogenicity, Kidney Diseases virology, Kidney Transplantation adverse effects, Kidney Transplantation methods, Living Donors, Opportunistic Infections virology, Polyomavirus Infections virology, Tumor Virus Infections virology
- Abstract
Background: BK virus (BKV) nephropathy remains the main cause of renal graft loss after living-donor renal transplantation. The aim of the study was to investigate the source and factors influencing the course of BKV infection., Methods: We investigated 214 living donor-recipient pairs. Urine and blood of donors and recipients were tested by qPCR for the presence of BKV DNA before and after transplantation; genotyping of BKV subtypes was performed., Results: Eighty-five recipients (40%) had posttransplant BK viruria including 61 with additional viremia and 22 with nephropathy. Pretransplant urinary BKV shedding of donor or recipient was a significant risk factor for posttransplant viruria and viremia (OR, 4.52; CI, 2.33-8.77; P < 0.0001) and nephropathy (OR, 3.03; CI, 1.16-7.9; P = 0.02). In the BKV nephropathy group, urine and blood became BKV positive earlier than in the group with viruria and viremia. Renal function was worse in BKV-nephropathy compared with BKV-negative patients beginning at transplantation. Comparing BKV subtypes of donor and recipient before with the subtype of the infected recipient after transplantation, donor-derived transmission was identified in 24 of 28 corresponding pairs. BKV subtype IV had a higher prevalence in recipients with BKV nephropathy than in those with viruria and viremia (P = 0.045)., Conclusions: Pretransplant urinary BKV shedding of donor and recipient is a risk for posttransplant infection. Donor-derived BKV transmission is an important mode of infection. BKV subtype IV may be one of the viral determinants. Early BKV positivity of urine and blood indicates later BKV nephropathy. Decreased renal function may favor BKV infection.
- Published
- 2016
- Full Text
- View/download PDF
19. Risk Factors for BK Polyoma Virus Treatment and Association of Treatment With Kidney Transplant Failure: Insights From a Paired Kidney Analysis.
- Author
-
Thangaraju S, Gill J, Wright A, Dong J, Rose C, and Gill J
- Subjects
- Adolescent, Adult, Age Factors, BK Virus pathogenicity, Female, HLA Antigens immunology, Histocompatibility, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Kaplan-Meier Estimate, Kidney Diseases diagnosis, Kidney Diseases immunology, Kidney Diseases virology, Kidney Transplantation mortality, Male, Middle Aged, Opportunistic Infections diagnosis, Opportunistic Infections immunology, Opportunistic Infections mortality, Opportunistic Infections virology, Polyomavirus Infections diagnosis, Polyomavirus Infections immunology, Polyomavirus Infections mortality, Proportional Hazards Models, Registries, Risk Adjustment, Risk Factors, Sex Factors, Time Factors, Tissue Donors, Treatment Failure, Tumor Virus Infections diagnosis, Tumor Virus Infections immunology, Tumor Virus Infections mortality, Tumor Virus Infections virology, Viral Load, Young Adult, Antiviral Agents therapeutic use, BK Virus drug effects, Kidney Diseases drug therapy, Kidney Transplantation adverse effects, Kidney Transplantation methods, Opportunistic Infections drug therapy, Polyomavirus Infections drug therapy, Polyomavirus Infections virology, Tumor Virus Infections drug therapy
- Abstract
Background: Identification of risk factors for BK polyoma virus (BKPyV) without confounding by donor factors and era effects in paired analysis may inform strategies to prevent BKPyV., Methods: In this analysis of 21,575 mate kidney pairs in the Scientific Registry of Transplant Recipients between 2004 and 2010, the presence of a treatment code for BKPyV virus in follow-up forms was used to identify pairs in which 1 of 2 mate kidneys was treated (discordant treatment) or both mate kidneys were treated (concordant treatment)., Results: Among 1975 discordant pairs, younger than 18 years or 60 years or older, male sex, HLA mismatch or 4 greater, acute rejection, and depleting antibody induction had a higher odds of treatment, whereas diabetes and sirolimus had a lower odds of treatment, and treatment was associated with a higher risk of allograft failure (hazards ratio, 2.01; 95% confidence interval, 1.63-2.48). The rate of concordant treatment (0.81%) was 2.8 times higher than expected. Concordant treatment was associated with nonwhite donor ethnicity, donation after circulatory death, transplantation after 2008, and transplantation of mate kidneys in the same center., Conclusions: This analysis of kidneys from the same donor in which only 1 transplant was treated for BKPyV identifies specific risk factors (age <18 or ≥ 60 years, male sex, depleting antibody, HLA mismatch ≥ 4) for BKPyV and provides an estimate of the BKPyV-associated risk of allograft failure (hazards ratio = 2.01) without confounding by donor factors or era effects. The higher than expected rate of concordant treatment suggests the importance of donor factors in BKPyV pathogenesis and warrants further study.
- Published
- 2016
- Full Text
- View/download PDF
20. What We Learned From Plasma BK-Virus Monitoring in Allogeneic Hematopoietic Transplant Recipients.
- Author
-
Ghosh A, Tan TT, Linn YC, Gopalakrishnan S, Goh YT, Hwang W, Tan BH, Ho A, and Phipps C
- Subjects
- BK Virus immunology, Biomarkers blood, Capsid Proteins blood, Cystitis blood, Cystitis virology, DNA, Viral blood, Hemorrhage blood, Hemorrhage virology, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Opportunistic Infections blood, Opportunistic Infections diagnosis, Opportunistic Infections immunology, Polymerase Chain Reaction, Polyomavirus Infections blood, Polyomavirus Infections diagnosis, Polyomavirus Infections immunology, Predictive Value of Tests, Prospective Studies, Time Factors, Transplantation, Homologous, Tumor Virus Infections blood, Tumor Virus Infections diagnosis, Tumor Virus Infections immunology, Viral Load, BK Virus genetics, Capsid Proteins genetics, DNA, Viral genetics, Hematopoietic Stem Cell Transplantation adverse effects, Opportunistic Infections virology, Polyomavirus Infections virology, Tumor Virus Infections virology
- Published
- 2016
- Full Text
- View/download PDF
21. Clinical Utility of Urinary Cytology to Detect BK Viral Nephropathy.
- Author
-
Nankivell BJ, Renthawa J, Jeoffreys N, Kable K, O'Connell PJ, Chapman JR, Wong G, and Sharma RN
- Subjects
- Adult, Antigens, Polyomavirus Transforming urine, Area Under Curve, BK Virus genetics, Biomarkers urine, Biopsy, Case-Control Studies, DNA, Viral urine, Female, Humans, Immunohistochemistry, Male, Middle Aged, New South Wales epidemiology, Polyomavirus Infections epidemiology, Polyomavirus Infections urine, Polyomavirus Infections virology, Predictive Value of Tests, Prevalence, Prospective Studies, ROC Curve, Tumor Virus Infections epidemiology, Tumor Virus Infections urine, Tumor Virus Infections virology, Urinary Tract Infections epidemiology, Urinary Tract Infections urine, Urinary Tract Infections virology, Urine cytology, Urine virology, Virus Activation, Virus Replication, BK Virus pathogenicity, Kidney Transplantation adverse effects, Pancreas Transplantation adverse effects, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis, Urinalysis methods, Urinary Tract Infections diagnosis
- Abstract
Background: Reactivation of BK polyoma virus can result in destructive viral allograft nephropathy (BKVAN) with limited treatment options. Screening programs using surrogate markers of viral replication are important preventive strategies, guiding immunosuppression reduction., Methods: We prospectively evaluated the diagnostic test performance of urinary decoy cells and urinary SV40T immunochemistry of exfoliated cells, to screen for BKVAN, (defined by reference histology with SV40 immunohistochemistry, n = 704 samples), compared with quantitative viremia, from 211 kidney and 141 kidney-pancreas transplant recipients., Results: The disease prevalence of BKVAN was 2.6%. Decoy cells occurred in 95 of 704 (13.5%) samples, with a sensitivity of 66.7%, specificity of 88.6%, positive predictive value (PPV) of 11.7%, and negative predictive value of 98.5% to predict histologically proven BKVAN. Quantification of decoy cells improved the PPV to 32.1% (10 ≥ cells threshold). Immunohistochemical staining of urinary exfoliated cells for SV40T improved sensitivity to 85.7%, detecting atypical or degenerate infected cells (specificity of 92.3% and PPV of 33.3%), but was hampered by technical failures. Viremia occurred in 90 of 704 (12.8%) with sensitivity of 96.3%, specificity of 90.3%, PPV of 31.5%, and negative predictive value of 99.8%. The receiver-operator curve performance of quantitative viremia surpassed decoy cells (area under the curve of 0.95 and 0.79, respectively, P = 0.0018 for differences). Combining decoy cell and BK viremia in a diagnostic matrix improved prediction of BKVAN and diagnostic risk stratification, especially for high-level positive results., Conclusions: Although quantified decoy cells are acceptable surrogate markers of BK viral replication with unexceptional test performances, quantitative viremia displayed superior test characteristics and is suggested as the screening test of choice.
- Published
- 2015
- Full Text
- View/download PDF
22. Polyomavirus nephropathy: quantitative urinary polyomavirus-Haufen testing accurately predicts the degree of intrarenal viral disease.
- Author
-
Singh HK, Reisner H, Derebail VK, Kozlowski T, and Nickeleit V
- Subjects
- Antigens, Polyomavirus Transforming chemistry, Biopsy, Graft Survival, Humans, Polymerase Chain Reaction, Polyomavirus physiology, Reproducibility of Results, Virus Replication, DNA, Viral urine, Kidney Diseases diagnosis, Kidney Diseases virology, Polyomavirus Infections diagnosis, Viremia urine, Viremia virology
- Abstract
Background: A qualitative highly predictive urinary test for polyomavirus nephropathy (PVN) is the PV-Haufen test. This article evaluates whether a quantitative PV-Haufen analysis, that is, the number of PV-Haufen shed per milliliter urine, predicts PVN disease grades and the severity of intrarenal PV replication., Methods: Polyomavirus-Haufen were counted in 40 urine samples from patients with biopsy-proven definitive PVN. The number of PV-Haufen was correlated with both histologic PVN disease grades 1 to 3 and the number of SV40-T-expressing cells as indicators of intrarenal PV replication in corresponding renal allograft biopsies (manual counts and automated morphometry). Findings from quantitative PV-Haufen analyses were compared to conventional laboratory test results, that is, BK viremia (quantitative polymerase chain reaction [PCR]) and BK viruria (quantitative PCR and decoy cell counts)., Results: Polyomavirus-Haufen counts showed excellent correlation (α0.77-0.86) with the severity of intrarenal PV replication and disease grades. In particular, low PV-Haufen numbers strongly correlated with early PVN grade 1 and minimal intrarenal expression of SV40-T antigen (P < 0.001). In comparison, BK viremia and viruria levels by PCR showed only modest correlations with histologic SV40-T expression (α0.40-0.49) and no significant correlation with disease grades or minimal intrarenal PV replication. No correlations were seen with urinary decoy cell counts. In contrast to conventional quantitative PCR assays or decoy cell counts, quantitative urinary PV-Haufen testing accurately reflects the severity of PV replication, tissue injury, and PVN disease grades., Conclusions: Quantitative PV-Haufen testing is a novel noninvasive approach to patient management for the diagnosis and prediction of PVN disease grades and monitoring of disease course during therapy.
- Published
- 2015
- Full Text
- View/download PDF
23. ABO-incompatible kidney transplantation is a novel risk factor for BK nephropathy.
- Author
-
Bentall A, Neil D, Sharif A, and Ball S
- Subjects
- Adult, BK Virus immunology, Biopsy, Blood Group Incompatibility immunology, Female, Humans, Immunosuppressive Agents adverse effects, Kidney immunology, Kidney pathology, Kidney virology, Kidney Diseases diagnosis, Kidney Diseases immunology, Kidney Diseases virology, Male, Middle Aged, Polyomavirus Infections diagnosis, Polyomavirus Infections immunology, Polyomavirus Infections virology, Risk Factors, Time Factors, Treatment Outcome, Tumor Virus Infections diagnosis, Tumor Virus Infections immunology, Tumor Virus Infections virology, Urinary Tract Infections diagnosis, Urinary Tract Infections immunology, Urinary Tract Infections virology, ABO Blood-Group System immunology, BK Virus pathogenicity, Blood Group Incompatibility complications, Kidney Diseases etiology, Kidney Transplantation adverse effects, Polyomavirus Infections etiology, Tumor Virus Infections etiology, Urinary Tract Infections etiology
- Published
- 2015
- Full Text
- View/download PDF
24. Polyomavirus-cystitis associated with in situ and invasive urothelial carcinoma in a heart transplant recipient: evidence suggesting sequential progression/evolution from infection to carcinoma.
- Author
-
Alexiev BA, Drachenberg CB, and Papadimitriou JC
- Subjects
- Aged, Biomarkers, Tumor analysis, Biopsy, Carcinoma chemistry, Carcinoma pathology, Carcinoma surgery, Cystectomy, Cystitis diagnosis, Disease Progression, Female, Humans, Immunohistochemistry, Polyomavirus Infections diagnosis, Reoperation, Treatment Outcome, Tumor Virus Infections diagnosis, Urinary Bladder Neoplasms chemistry, Urinary Bladder Neoplasms pathology, Urinary Bladder Neoplasms surgery, Urothelium chemistry, Urothelium pathology, Carcinoma virology, Cell Transformation, Viral, Cystitis virology, Heart Transplantation adverse effects, Polyomavirus pathogenicity, Polyomavirus Infections virology, Tumor Virus Infections virology, Urinary Bladder Neoplasms virology, Urothelium virology
- Published
- 2015
- Full Text
- View/download PDF
25. Screening for BK viremia.
- Author
-
AlBugami MM and Kiberd BA
- Subjects
- Female, Humans, Male, BK Virus isolation & purification, Immunosuppressive Agents adverse effects, Kidney Diseases prevention & control, Kidney Transplantation immunology, Mass Screening, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis, Viremia diagnosis
- Published
- 2013
- Full Text
- View/download PDF
26. Screening for BK viremia reduces but does not eliminate the risk of BK nephropathy.
- Author
-
Knight RJ, Gaber LW, Patel SJ, DeVos JM, Moore LW, and Gaber AO
- Subjects
- Female, Humans, Male, BK Virus isolation & purification, Immunosuppressive Agents adverse effects, Kidney Diseases prevention & control, Kidney Transplantation immunology, Mass Screening, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis, Viremia diagnosis
- Published
- 2013
- Full Text
- View/download PDF
27. A rapid noninvasive assay for the detection of renal transplant injury.
- Author
-
Sigdel TK, Vitalone MJ, Tran TQ, Dai H, Hsieh SC, Salvatierra O, and Sarwal MM
- Subjects
- Acute Disease, Adolescent, Adult, Apoptosis, BK Virus genetics, Biomarkers blood, Biomarkers urine, Child, DNA blood, DNA Copy Number Variations, Female, Graft Rejection drug therapy, Graft Rejection metabolism, Humans, Immunosuppressive Agents therapeutic use, Male, Polyomavirus Infections diagnosis, Reperfusion Injury metabolism, Sensitivity and Specificity, Sex Factors, Transplantation, Homologous, Tumor Virus Infections diagnosis, Young Adult, Chromosomes, Human, Y, Graft Rejection diagnosis, Kidney Transplantation adverse effects, Reperfusion Injury diagnosis
- Abstract
Background: The copy number of donor-derived cell-free DNA (dd-cfDNA) in blood correlates with acute rejection (AR) in heart transplantation. We analyzed urinary dd-cfDNA as a surrogate marker of kidney transplant injury., Methods: Sixty-three biopsy-matched urine samples (41 stable and 22 allograft injury) were analyzed from female recipients of male donors for chromosome Y (donor)-specific dd-cfDNA. All biopsies were semiquantitatively scored by a single pathologist. Standard statistical measures of correlation and significance were used., Results: There was baseline scatter for urinary dd-cfDNA/μg urine creatinine across different patients, even at the time of stable graft (STA) function (undetected to 12.26 copies). The mean urinary dd-cfDNA in AR (20.5 ± 13.9) was significantly greater compared with STA (2.4 ± 3.3; P<0.0001) or those with chronic allograft injury (CAI; 2.4 ± 2.4; P=0.001) but no different from BK virus nephropathy (BKVN; 20.3±15.7; P=0.98). In AR and BKVN, the intrapatient drift was highly significant versus STA or CAI patients (10.3 ± 7.4 in AR; 12.3 ± 8.4 in BKVN vs. -0.5 ± 3.5 in STA and 2.3 ± 2.6 in CAI; P<0.05). Urinary dd-cfDNA correlated with protein/creatinine ratio (r=0.48; P<0.014) and calculated glomerular filtration rate (r=-0.52; P<0.007) but was most sensitive for acute allograft injury (area under the curve=0.80; P<0.0006; 95% confidence interval, 0.67-0.93)., Conclusion: Urinary dd-cfDNA after renal transplantation has patient specific thresholds, reflecting the apoptotic injury load of the donor organ. Serial monitoring of urinary dd-cfDNA can be a surrogate sensitive biomarker of acute injury in the donor organ but lacks the specificity to distinguish between AR and BKVN injury.
- Published
- 2013
- Full Text
- View/download PDF
28. Risk factors for BK virus infection in the era of therapeutic drug monitoring.
- Author
-
Borni-Duval C, Caillard S, Olagne J, Perrin P, Braun-Parvez L, Heibel F, and Moulin B
- Subjects
- Adolescent, Adult, Aged, Area Under Curve, Biopsy, Female, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents therapeutic use, Kidney Transplantation adverse effects, Male, Middle Aged, Mycophenolic Acid administration & dosage, Mycophenolic Acid adverse effects, Mycophenolic Acid analogs & derivatives, Renal Insufficiency complications, Risk Factors, Steroids administration & dosage, Tacrolimus administration & dosage, Tacrolimus adverse effects, Viremia epidemiology, Young Adult, BK Virus isolation & purification, Drug Monitoring methods, Immunosuppressive Agents adverse effects, Kidney Transplantation methods, Polyomavirus Infections diagnosis, Renal Insufficiency therapy
- Abstract
Background: Overimmunosuppression is a widely recognized risk factor for BK virus (BKV) infection, particularly with the combination of tacrolimus, mycophenolate mofetil (MMF), and steroids. Nevertheless, the exact impact of exposure to tacrolimus and MMF is not well understood., Methods: We examined 240 kidney recipients between 2006 and 2008. BKV was monitored every 2 months in the urine or blood. A kidney biopsy was performed when viremia exceeded 10 copies/mL., Results: Ninety-five (40%) patients had sustained viruria, 48 (20%) sustained viremia, and 17 (7%) biopsy-proven polyomavirus-associated nephropathy. The mean time-to-occurrence was 7.6, 7.9, and 9.7 months for viruria, viremia, and polyomavirus-associated nephropathy. Risk factors associated with BKV infection in univariate analyses were retransplantation, panel-reactive antibody more than 0%, cytomegalovirus D+/R-, cold ischemia time, delayed graft function, induction with antithymocyte globulins, acute rejection before month 3 (M3), tacrolimus trough levels more than 10 ng/mL, and M3 AUC0-12 hr more than 50 hr mg/L. Multivariate analyses showed that cytomegalovirus D+/R- (adjusted hazard ratio [AHR], 2.03; P=0.05), acute rejection (AHR, 5.4; P<0.001), and mycophenolic acid AUC0-12 hr more than 50 hr mg/L (AHR, 3.6; P=0.001) were risk factors for BKV., Conclusions: This study identified a link between a state of increased immunosuppression and BKV infection, especially in patients with higher MMF exposure and elevated tacrolimus trough levels at M3.
- Published
- 2013
- Full Text
- View/download PDF
29. Screening for BK viremia reduces but does not eliminate the risk of BK nephropathy: a single-center retrospective analysis.
- Author
-
Knight RJ, Gaber LW, Patel SJ, DeVos JM, Moore LW, and Gaber AO
- Subjects
- Adult, Antiviral Agents therapeutic use, BK Virus genetics, Biopsy, Cidofovir, Cytosine analogs & derivatives, Cytosine therapeutic use, Early Diagnosis, Female, Glomerular Filtration Rate, Graft Survival, Humans, Kaplan-Meier Estimate, Kidney Diseases diagnosis, Kidney Diseases immunology, Kidney Diseases virology, Kidney Transplantation adverse effects, Logistic Models, Male, Middle Aged, Multivariate Analysis, Organophosphonates therapeutic use, Polyomavirus Infections immunology, Polyomavirus Infections virology, Predictive Value of Tests, Retrospective Studies, Risk Assessment, Risk Factors, Texas, Time Factors, Tumor Virus Infections immunology, Tumor Virus Infections virology, Viral Load, Viremia immunology, Viremia virology, Young Adult, BK Virus isolation & purification, Immunosuppressive Agents adverse effects, Kidney Diseases prevention & control, Kidney Transplantation immunology, Mass Screening methods, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis, Viremia diagnosis
- Abstract
Background: This study reviewed the outcomes of a screening protocol for BK viremia to determine if early diagnosis, followed by immunosuppression minimization, would prevent progression to nephropathy and graft loss., Methods: This review included 369 renal transplant recipients tested for BK virus at serial time points after transplantation. Management included immunosuppression minimization plus cidofovir treatment for BK nephropathy., Results: Recipients received tacrolimus-based immunosuppression, with 8% prednisone-free and 6% who received desensitization. With a mean follow-up of 22 ± 10 months, 16% (n = 57) of recipients became BK viremia positive. The median (range) time to diagnosis was 3 (1-17) months. Because renal biopsy was performed selectively, 59% of recipients underwent biopsy, with 47% showing BK nephropathy. Seventy-four percent of recipients cleared the virus at a median (range) time of 9 (3-33) months, with four grafts lost to BK nephropathy. Cidofovir-treated recipients displayed a higher viral load at diagnosis but showed equivalent renal function at last evaluation. In multivariate analysis, recipient age, Asian ethnicity, deceased donor, and prednisone use were factors independently associated with BK viremia. Actuarial survival of BK-positive grafts was worse than that of BK-negative grafts (P<0.01, log-rank test). At 9 and 12 months, the mean estimated glomerular filtration rate of the BK-positive group was lower than that of the BK-negative cohort (P = 0.02)., Conclusions: Despite using a screening protocol combined with immunosuppression minimization, BK-positive recipients had a greater risk of graft loss and impaired function than recipients free of infection. Future investigations should focus on practices to prevent BK viremia.
- Published
- 2013
- Full Text
- View/download PDF
30. Risk assessment for polyomavirus nephropathy using urine cytology and the detection of decoy cells: cheap and efficient.
- Author
-
Nickeleit V, True K, Detwiler R, Kozlowski T, and Singh H
- Subjects
- Humans, BK Virus isolation & purification, Cytological Techniques economics, Kidney Transplantation, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis, Urine cytology, Urine virology
- Published
- 2012
- Full Text
- View/download PDF
31. Detection of polyomavirus BK reactivation after renal transplantation using an intensive decoy cell surveillance program is cost-effective.
- Author
-
Chakera A, Dyar OJ, Hughes E, Bennett S, Hughes D, and Roberts IS
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cost-Benefit Analysis, Cytological Techniques methods, Follow-Up Studies, Graft Rejection etiology, Graft Rejection virology, Humans, Immunosuppression Therapy, Infant, Middle Aged, Polymerase Chain Reaction, Polyomavirus Infections complications, Polyomavirus Infections urine, Retrospective Studies, Transplantation, Homologous, Tumor Virus Infections complications, Tumor Virus Infections urine, Young Adult, BK Virus isolation & purification, Cytological Techniques economics, Kidney Transplantation immunology, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis, Urine cytology, Urine virology
- Abstract
Background: Reactivation of polyomavirus BK (BKV) after renal transplantation can lead to allograft dysfunction or loss with early detection improving outcomes. Current guidelines recommend quantitative polymerase chain reaction for surveillance; however, urinary decoy cell detection is a potentially cost-effective alternative. We present the outcomes from an early intensive BKV surveillance program using decoy cell detection for initial screening starting 2 weeks after transplantation., Methods: Records for all recipients of kidney (n=211) or simultaneous kidney and pancreas (n=102) transplants performed over 2 years in a single center were reviewed. Follow-up was for a minimum of 1 year. Urine cytology screening was performed fortnightly from 0 to 3 months after transplantation, monthly from 3 to 6 months then every 2 months from 6 to 12 months., Results: Decoy cell positivity occurred in 56 of 313 patients (17.9%) with sustained decoy cell positivity (≥2 positive urine samples >2 weeks apart) present in 32 patients (10.2%). Twenty-four patients (7.6%) became viremic and three patients (1%) developed polyoma virus nephropathy. The median time after transplantation until decoy cell positivity was 78 days, decreasing to 67 days for patients with sustained positivity and 57 days for patients who developed polyoma virus nephropathy. No grafts were lost due to BKV during the study period. Decoy cell screening resulted in savings of approximately £135,000 over 2 years, when compared with routine surveillance by quantitative polymerase chain reaction., Conclusions: Clinically significant BKV reactivation occurs early after transplantation and can be reliably detected by decoy cell screening. A surveillance strategy for detecting BKV reactivation based on urine cytology is cost-effective.
- Published
- 2011
- Full Text
- View/download PDF
32. Preemptive retransplant for BK virus nephropathy without concurrent transplant nephrectomy.
- Author
-
Cooper JE, Huskey J, Chan L, and Wiseman AC
- Subjects
- Aged, Biopsy, Female, Humans, Immunosuppressive Agents adverse effects, Nephritis, Interstitial diagnosis, Nephritis, Interstitial virology, Polyomavirus Infections diagnosis, Polyomavirus Infections surgery, Reoperation, Time Factors, Transplantation, Homologous, Treatment Outcome, Virus Replication, BK Virus pathogenicity, Kidney Transplantation adverse effects, Nephritis, Interstitial surgery, Polyomavirus Infections virology
- Published
- 2010
- Full Text
- View/download PDF
33. Validation of noninvasive diagnosis of BK virus nephropathy and identification of prognostic biomarkers.
- Author
-
Dadhania D, Snopkowski C, Ding R, Muthukumar T, Lee J, Bang H, Sharma VK, Seshan S, August P, Kapur S, and Suthanthiran M
- Subjects
- Adult, BK Virus genetics, Biopsy, Creatinine blood, Cross-Sectional Studies, Female, Gene Amplification, Graft Rejection diagnosis, Graft Rejection pathology, Graft Rejection urine, Graft Rejection virology, Graft Survival, Humans, Male, Middle Aged, Polymerase Chain Reaction methods, Polyomavirus Infections epidemiology, Prognosis, RNA, Messenger genetics, RNA, Messenger urine, RNA, Ribosomal, 18S genetics, RNA, Ribosomal, 18S urine, RNA, Viral genetics, RNA, Viral urine, Reproducibility of Results, Transplantation, Homologous, Tumor Virus Infections epidemiology, BK Virus isolation & purification, Kidney Transplantation adverse effects, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis
- Abstract
Background: BK virus nephropathy (BKVN) may cause renal allograft dysfunction and failure. The gold standard test is kidney biopsy, which is invasive and costly. A noninvasive, accurate biomarker for diagnosis of BKVN and prognostication of allograft function after BKVN infection may improve allograft survival., Methods: We tested the diagnostic accuracy of our previously reported cutoff value of 6.5x10(5) BKV viral capsid protein 1 (VP-1) mRNA/ng RNA in urinary cells (Ding et al., Transplantation 2002; 74: 987) using an independent cohort (n=89). We also examined whether urinary cell mRNA profiles obtained at the time of BKVN diagnosis identified patients at risk of subsequent decline in graft function., Results: BKVN was accurately diagnosed (sensitivity of 100% and specificity of 97%) using our previously reported cutoff value. Levels of granzyme B (GB) mRNA (P=0.002) and proteinase inhibitor (PI)-9 mRNA (P=0.01) in urinary cells were higher in BKVN patients with a subsequent decline in renal function (n=8) compared with patients with stable function (n=10), and were positively associated (GB, P=0.01; PI-9, P=0.04) with rise in serum creatinine from the time of BKVN diagnosis to 12 months after diagnosis. GB levels in the BKVN patients with a decline in renal function were similar to those in the acute rejection group (n=11, P>0.05), but higher than the normal biopsy group (n=36, P<0.001); levels in BKVN patients with stable function were lower than those in the acute rejection group (P<0.01) and not significantly different from the normal biopsy group (P>0.05)., Conclusions: Noninvasive diagnosis of BKVN and prognostication of renal allograft function after BKVN diagnosis are feasible by measurement of transcripts for BKV viral capsid protein 1 (VP-1), GB, and PI-9 in urine.
- Published
- 2010
- Full Text
- View/download PDF
34. Respiratory epithelium: an unlikely reservoir for latent human polyomavirus infection but a likely portal of entry.
- Author
-
Keating DT, Michaelides A, Mifsud NA, Bowden S, and Kotsimbos TC
- Subjects
- Adolescent, Adult, Central Nervous System Diseases virology, Child, Disease Reservoirs, Humans, Lung Transplantation adverse effects, Polyomavirus physiology, Polyomavirus Infections epidemiology, Urologic Diseases virology, Polyomavirus Infections diagnosis, Respiratory Mucosa virology, Virus Activation
- Published
- 2010
- Full Text
- View/download PDF
35. Sustained BK viruria as an early marker for the development of BKV-associated nephropathy: analysis of 4128 urine and serum samples.
- Author
-
Babel N, Fendt J, Karaivanov S, Bold G, Arnold S, Sefrin A, Lieske E, Hoffzimmer M, Dziubianau M, Bethke N, Meisel C, Grütz G, and Reinke P
- Subjects
- Adult, BK Virus genetics, Cross-Sectional Studies, DNA, Viral blood, DNA, Viral urine, Early Diagnosis, Female, Humans, Kaplan-Meier Estimate, Kidney Diseases blood, Kidney Diseases drug therapy, Kidney Diseases urine, Kidney Diseases virology, Logistic Models, Male, Middle Aged, Polymerase Chain Reaction, Polyomavirus Infections blood, Polyomavirus Infections drug therapy, Polyomavirus Infections urine, Polyomavirus Infections virology, Predictive Value of Tests, Prevalence, Prospective Studies, Reproducibility of Results, Risk Assessment, Sensitivity and Specificity, Time Factors, Viral Load, Viremia diagnosis, Virus Activation, BK Virus isolation & purification, DNA, Viral isolation & purification, Kidney Diseases diagnosis, Kidney Transplantation adverse effects, Polyomavirus Infections diagnosis
- Abstract
Background: BKV reactivation plays the causative role in the development of BKV-associated nephropathy (BKVAN). Because of the lack of effective therapy, early diagnosis of BKV reactivation is paramount for the prevention of BKVAN. Resting in uroepithelial cells, BKV is excreted first in urine before it can be detected in plasma. The present study analyzed predictive value of BK viruria for the development of BK viremia and its possible advantage for the early BKVAN prediction., Methods: Total of 4128 urine and serum samples obtained from renal transplant patients were analyzed for BKV positivity by real-time polymerase chain reaction in 433 patients in cross-sectional and in 233 patients in longitudinal manner, respectively. The prospective longitudinal analysis included seven measurements during the first posttransplant year., Results: A total of 7% and 19% patients were positive for BKV in serum and urine, respectively. Sustained BK viruria showed sensitivity of 100% and specificity of 94% for BK viremia and was associated with significantly higher level of BK load than the patients with transient viruria (P<0.01). Interestingly, BK viremia was preceded by BK viruria: the peak of viral load and number of positive patients appeared during the third and fifth posttransplant month for urine and serum, respectively. BKVAN diagnosed in 21.4% of patient with persistent BK viruria appeared 5 and 11 weeks after BKV reactivation in serum and urine, respectively, was detected., Conclusion: Sustained BK viruria is a reliable marker allowing an early identification of patients at high risk of BKVAN development and therefore assure precocious therapeutic interventions.
- Published
- 2009
- Full Text
- View/download PDF
36. Prospective monitoring of BK polyomavirus infection early posttransplantation in nonrenal solid organ transplant recipients.
- Author
-
Doucette KE, Pang XL, Jackson K, Burton I, Carbonneau M, Cockfield S, and Preiksaitis JK
- Subjects
- Adult, Female, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Polyomavirus Infections blood, Polyomavirus Infections epidemiology, Postoperative Complications, Prospective Studies, Risk Factors, Tumor Virus Infections blood, Tumor Virus Infections epidemiology, Viral Load, BK Virus, Heart Transplantation, Liver Transplantation, Lung Transplantation, Polyomavirus Infections diagnosis, Renal Insufficiency virology, Tumor Virus Infections diagnosis
- Abstract
Background: BK virus-associated nephropathy is an important cause of renal dysfunction in renal transplant recipients. Renal dysfunction after nonrenal solid organ transplantation (NRSOT) is common; however, the impact of BK virus remains uncertain., Methods: Sixty (7 heart, 25 liver, and 28 lung) NRSOT recipients were enrolled in this single center prospective longitudinal study. Urine and plasma were collected for detection of BK viral load using a real-time quantitative polymerase chain reaction assay at transplantation and at 3, 6, and 9 months posttransplantation. Demographic and clinical data including serum creatinine and immunosuppressive therapy were also collected., Results: BK viruria was detected in 16 of 193 (8.3%) samples corresponding to 9 of 60 (15%) subjects. The median BK viral load was 1.12 x 10 (range, 1.1 x 10-2.66 x 10) copies per milliliter. No viremia was detected. In seven of nine, viruria occurred by 3 months posttransplantation. At 9 months of posttransplantation, the median Modification of Diet in Renal Disease-estimated glomerular filtration rate in those with BK viruria on at least one sample was similar to those without viruria (58.0 [IQR 43.1-60.7] mL/min/1.73 m vs. 61.4 [IQR 50.6-74.4] mL/min/1.73 m; P=0.39)., Conclusions: Although BK infection was common in this NRSOT population, BK viremia was not observed and there was no association between BK viruria and renal dysfunction. Our data suggest that routine surveillance for BK virus early posttransplantation in NRSOT may not be warranted but should be further examined in a larger multicenter trial.
- Published
- 2008
- Full Text
- View/download PDF
37. Polyomavirus in renal transplantation: a hot problem.
- Author
-
Bonvoisin C, Weekers L, Xhignesse P, Grosch S, Milicevic M, and Krzesinski JM
- Subjects
- BK Virus immunology, Humans, Immunosuppressive Agents immunology, Kidney pathology, Kidney virology, Opportunistic Infections diagnosis, Polyomavirus Infections diagnosis, Polyomavirus Infections immunology, Tumor Virus Infections diagnosis, Tumor Virus Infections immunology, BK Virus pathogenicity, Kidney Transplantation immunology, Opportunistic Infections immunology
- Abstract
Polyomavirus BK has emerged as an important complication after kidney transplantation. Although, BK nephropathy develops in only 1% to 5% of renal transplant recipients, its prognosis when present is very poor. The most accepted risk factor is the level of immunosuppressive treatment, but the serostatus of donor and recipient and the absence of human leukocyte antigen C7 in donor and/or recipient influence the BK virus (BKV) reactivation. The gold standard in diagnosing BKV nephropathy (BKVN) continues to be biopsy with use of immunohistochemistry for large T antigens. Urinary decoy cells and blood BKV DNA polymerase chain reaction are used in the screening, but their positive predictive values are poor. However, their use as predictors of the evolution of BKVN is more valuable. The reduction of immunosuppressive therapy currently represents the first-line treatment for BKVN. Cidofovir and leflunomide can be used when BKVN continues to progress. In the event of graft loss, retransplantation is possible with a low risk of recurrence when the infection is no longer active.
- Published
- 2008
- Full Text
- View/download PDF
38. Polyomavirus polymerase chain reaction as a surrogate marker of polyomavirus-associated nephropathy.
- Author
-
Viscount HB, Eid AJ, Espy MJ, Griffin MD, Thomsen KM, Harmsen WS, Razonable RR, and Smith TF
- Subjects
- Adult, Aged, BK Virus pathogenicity, Biomarkers blood, Biomarkers urine, Biopsy, Cross-Sectional Studies, DNA, Viral blood, DNA, Viral genetics, DNA, Viral urine, Female, Humans, Kidney metabolism, Kidney pathology, Kidney virology, Kidney Diseases metabolism, Kidney Diseases pathology, Kidney Transplantation pathology, Male, Middle Aged, Polyomavirus Infections genetics, Polyomavirus Infections metabolism, Predictive Value of Tests, Sensitivity and Specificity, Tumor Virus Infections genetics, Tumor Virus Infections metabolism, Viral Load, BK Virus genetics, Kidney Diseases virology, Kidney Transplantation adverse effects, Polymerase Chain Reaction methods, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis
- Abstract
Background: Polyomavirus-associated nephropathy (PVAN) is a significant cause of allograft loss after renal transplantation. A noninvasive assay that can guide the evaluation of PVAN would be of clinical value. We compared the utility of BK virus (BKV) polymerase chain reaction (PCR) and urine cytology in screening for concurrent PVAN., Methods: We used PCR to test urine and plasma samples from renal recipients simultaneously for BKV DNA. Additionally, we tested urine samples for decoy cells. Sample results were correlated with biopsy-proven PVAN. Receiver-operator characteristic curves were used to determine viral load thresholds associated with concurrent PVAN., Results: In this cross-sectional study, BKV viruria, viremia, and urinary decoy cells were detected in 24%, 9%, and 13% of renal recipients, respectively. Among 114 patients who had renal allograft biopsy, four (3.5%) were diagnosed with PVAN. Using pathology as gold standard for the diagnosis of PVAN, BKV viremia threshold of >1.6E+04 copies/mL had 100% sensitivity, 96% specificity, 50% positive predictive value, and 100% negative predictive value. A BKV viruria threshold of >2.5E+07 copies/mL had 100% sensitivity, 92% specificity, 31% positive predictive value, and 100% negative predictive value. In contrast, urine decoy cells had 25% sensitivity, 84% specificity, 5% positive predictive value, and 97% negative predictive value for the diagnosis of concurrent PVAN., Conclusion: BKV PCR may be a clinically useful noninvasive test to identify renal recipients with concurrent PVAN. BKV DNA >1.6E+04 copies/mL of plasma and >2.5E+07 copies/mL of urine were highly associated with concurrent PVAN whereas a negative PCR test makes the diagnosis of PVAN highly unlikely.
- Published
- 2007
- Full Text
- View/download PDF
39. BK virus-related hemophagocytic syndrome in a renal transplant patient.
- Author
-
Esposito L, Hirsch H, Basse G, Fillola G, Kamar N, and Rostaing L
- Subjects
- Humans, Lymphohistiocytosis, Hemophagocytic virology, Male, Middle Aged, Treatment Outcome, BK Virus isolation & purification, Kidney Transplantation, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic therapy, Polyomavirus Infections diagnosis, Polyomavirus Infections therapy
- Published
- 2007
- Full Text
- View/download PDF
40. Low incidence of BK virus nephropathy after simultaneous kidney pancreas transplantation.
- Author
-
Gupta G, Shapiro R, Thai N, Randhawa PS, and Vats A
- Subjects
- Adult, Female, Graft Survival, Humans, Incidence, Male, Middle Aged, Nephritis diagnosis, Nephritis drug therapy, Nephritis epidemiology, Polyomavirus Infections diagnosis, Polyomavirus Infections drug therapy, Polyomavirus Infections virology, Transplantation, Homologous, Tumor Virus Infections diagnosis, Tumor Virus Infections drug therapy, Tumor Virus Infections virology, BK Virus physiology, Kidney Transplantation, Nephritis virology, Pancreas Transplantation, Polyomavirus Infections epidemiology, Tumor Virus Infections epidemiology
- Abstract
Background: BK virus renal allograft nephropathy (BKVAN) in the setting of simultaneous kidney-pancreas transplantation (SKPT) has been inadequately studied and reported. We analyzed our data on the incidence of BKVAN and its outcome in SKPT recipients at University of Pittsburgh Medical Center (UPMC) and affiliated centers and report significant differences compared to previous studies., Methods: This study used retrospective review and case studies., Results: A review of 243 consecutive SKPT recipients from January 1, 1996 to December 31, 2004 identified seven cases (three females; ages = 23-54 yrs) of BKVAN following SKPT (incidence = 2.9%). The immunosuppressive protocols during this period were divided into: Period I (pre-August 2001) with no antibody induction and Period II (post-August 2001) with alemtuzumab or antithymocyte globulin induction with steroid avoidance. One BKVAN case was diagnosed in Period II (incidence = 1.4%). Six of seven patients were treated with intravenous cidofovir (0.20-0.50 mg/kg) every two to four weeks over one to six months. Three patients lost the renal allograft 8-22 months following diagnosis of BKVAN, whereas four patients had prolonged allograft survival. Pancreatic function was well preserved in five; one patient lost the pancreatic function due to surgical complications and one has had partial preservation., Conclusions: There was a relatively lower incidence of BKVAN among SKPT patients at our center. Although overall graft loss rate was comparable to other series, BKVAN patients had a slightly prolonged graft life. The BKVAN incidence was further reduced in patients receiving modified immunosuppression with antibody preconditioning. The underlying reasons may include less toxic immunosuppressive protocols, earlier diagnosis and the use of antiviral therapy.
- Published
- 2006
- Full Text
- View/download PDF
41. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations.
- Author
-
Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP, Mihatsch MJ, Nickeleit V, Ramos E, Randhawa P, Shapiro R, Steiger J, Suthanthiran M, and Trofe J
- Subjects
- Humans, Kidney Diseases epidemiology, Kidney Diseases therapy, Polyomavirus Infections diagnosis, Risk Factors, Kidney Diseases surgery, Kidney Diseases virology, Kidney Transplantation, Polyomavirus Infections complications
- Abstract
Polyomavirus-associated nephropathy (PVAN) is an emerging cause of kidney transplant failure affecting 1-10% of patients. As uncertainty exists regarding risk factors, diagnosis, and intervention, an independent panel of experts reviewed the currently available evidence and prepared this report. Most cases of PVAN are elicited by BK virus (BKV) in the context of intense immunosuppression. No specific immunosuppressive drug is exclusively associated with PVAN, but most cases reported to date arise while the patient is on triple immunosuppressive combinations, often comprising tacrolimus and/or mycophenolate mofetil plus corticosteroids. Immunologic control of polyomavirus replication can be achieved by reducing, switching, and/or discontinuing components of the immunosuppressive regimen, but the individual's risk of rejection should be considered. The success rate of this intervention is increased with earlier diagnosis. Therefore, it is recommended that all renal transplant recipients should be screened for BKV replication in the urine: 1) every three months during the first two years posttransplant; 2) when allograft dysfunction is noted; and 3) when allograft biopsy is performed. A positive screening result should be confirmed in <4 weeks and assessed by quantitative assays (e.g. BKV DNA or RNA load in plasma or urine). Definitive diagnosis of PVAN requires allograft biopsy. If PVAN and concurrent acute rejection is diagnosed, antirejection treatment should be considered, coupled with subsequently reducing immunosuppression. The antiviral cidofovir is not approved for PVAN, but investigational use at low doses (0.25-0.33 mg/kg intravenously biweekly) without probenicid should be considered for refractory cases. Retransplantation after renal allograft loss to PVAN remains a treatment option for patients clearing polyomavirus replication.
- Published
- 2005
- Full Text
- View/download PDF
42. Monitoring for polyomavirus BK And JC in urine: comparison of quantitative polymerase chain reaction with urine cytology.
- Author
-
Randhawa P, Vats A, and Shapiro R
- Subjects
- BK Virus genetics, Humans, JC Virus genetics, Polyomavirus Infections diagnosis, Sensitivity and Specificity, BK Virus isolation & purification, JC Virus isolation & purification, Polymerase Chain Reaction methods, Polyomavirus Infections urine, Polyomavirus Infections virology, Urine cytology, Urine virology
- Abstract
Clinical monitoring for polyomavirus infection is becoming common, but the optimal detection technique remains undefined. We compared the relative efficacy of exfoliative cytology and polymerase chain reaction (PCR) for detecting viruria in 100 urine samples. Definite decoy cells were seen in 8% and probable decoy cells in 5% of specimens. PCR showed BK virus (BKV) DNA in all these and in an additional 18% of samples. Using decoy cells as a marker of polyomavirus viruria cytology has a sensitivity of 41.9% and negative predictive value of 82.8%. The specificity and positive predictive value for viruria (not viral nephropathy) are 100%. False-negative results occurred in samples with suboptimal cellularity, vaginal contamination, and a low viral load. One patient with a false-negative urine cytology developed BKV nephropathy on follow-up. Compared with PCR, urine cytology is a less sensitive technique, which requires morphologically intact cells, and cannot distinguish BKV from JC virus.
- Published
- 2005
- Full Text
- View/download PDF
43. Polyomavirus nephropathy: what have we learned?
- Author
-
Mannon RB
- Subjects
- Animals, Humans, Kidney Diseases virology, BK Virus, Kidney Transplantation, Polyomavirus Infections diagnosis, Polyomavirus Infections therapy, Tumor Virus Infections diagnosis, Tumor Virus Infections therapy
- Published
- 2004
- Full Text
- View/download PDF
44. The high incidence of BK polyoma virus infection among renal transplant recipients in India.
- Author
-
Sachdeva MS, Nada R, Jha V, Sakhuja V, and Joshi K
- Subjects
- Adolescent, Adult, Biopsy, Female, Humans, Immunohistochemistry, Incidence, India epidemiology, Kidney metabolism, Kidney pathology, Male, Microscopy, Electron, Middle Aged, Polyomavirus Infections diagnosis, Postoperative Period, Retrospective Studies, Tumor Virus Infections diagnosis, BK Virus, Kidney Transplantation statistics & numerical data, Polyomavirus Infections epidemiology, Tumor Virus Infections epidemiology
- Abstract
BK polyoma virus causes allograft dysfunction as a result of tubulo-interstitial nephritis in 2% to 5% of renal transplant recipients. The incidence of BK virus infection among renal transplant recipients in India is unknown. We used routine histologic examination, immunohistochemistry, and electron microscopy to retrospectively screen for BK polyoma virus in 414 renal allograft biopsy specimens from 321 transplant recipients presenting with allograft dysfunction. All patients had received a combination of cyclosporine, azathioprine, and prednisolone. A total of 30 biopsy specimens (9.3%) were positive for BK polyoma virus, suggesting a high incidence of this infection in Indian transplant recipients. BK virus infection coexisted with acute rejection in a majority of patients. This is the first report of this infection among Indian renal transplant recipients.
- Published
- 2004
- Full Text
- View/download PDF
45. Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK VP1 virus in urine.
- Author
-
Ding R and Suthanthiran M
- Subjects
- BK Virus isolation & purification, Capsid Proteins urine, Humans, Nephritis urine, Polyomavirus Infections urine, RNA, Messenger urine, RNA, Viral urine, Tumor Virus Infections urine, BK Virus genetics, Capsid Proteins genetics, Nephritis virology, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis
- Published
- 2003
- Full Text
- View/download PDF
46. VP1 messenger RNA levels in urine for diagnosing BK virus nephropathy?
- Author
-
Hirsch HH
- Subjects
- BK Virus isolation & purification, Humans, Kidney Diseases diagnosis, Polymerase Chain Reaction, Polyomavirus Infections pathology, BK Virus genetics, Capsid Proteins genetics, Kidney Diseases virology, Polyomavirus Infections diagnosis, RNA, Viral urine
- Published
- 2003
- Full Text
- View/download PDF
47. Re: noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1.
- Author
-
Nickeleit V, Steiger J, and Mihatsch MJ
- Subjects
- Humans, Nephritis diagnosis, Nephritis pathology, Polymerase Chain Reaction methods, RNA, Messenger genetics, Reproducibility of Results, BK Virus genetics, Capsid Proteins genetics, Nephritis virology, Polyomavirus Infections diagnosis, RNA, Messenger isolation & purification
- Published
- 2003
- Full Text
- View/download PDF
48. Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine.
- Author
-
Ding R, Medeiros M, Dadhania D, Muthukumar T, Kracker D, Kong JM, Epstein SR, Sharma VK, Seshan SV, Li B, and Suthanthiran M
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Nephritis urine, Polyomavirus Infections urine, ROC Curve, Tumor Virus Infections urine, Urine cytology, BK Virus genetics, Capsid physiology, Capsid Proteins, DNA, Viral urine, Nephritis virology, Polyomavirus Infections diagnosis, Tumor Virus Infections diagnosis
- Abstract
Background: Polyoma virus type BK (BKV) nephritis has emerged as an important cause of renal allograft dysfunction and graft failure. Its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for BKV nephritis could improve clinical outcome., Methods: We obtained 25 urine specimens from 8 renal allograft recipients with biopsy-confirmed BKV nephritis, 31 samples from 28 recipients in whom BKV nephritis was excluded by allograft biopsy, and 74 specimens from 34 patients with stable allograft function. RNA was isolated from the urinary cells and reverse transcribed to complementary DNA. We designed gene-specific oligonucleotide primers and probes for the measurement of messenger RNA (mRNA) encoding BKV VP1 protein and a constitutively expressed 18S ribosomal RNA (rRNA) by real-time quantitative polymerase chain reaction. We explored the hypothesis that BKV VP1 mRNA levels predict BKV nephritis., Results: The levels of BKV VP1 mRNA but not the levels of 18S rRNA predicted BKV nephritis. Analysis involving the receiver operating characteristic curve demonstrated that BKV nephritis can be predicted with a sensitivity of 93.8% and a specificity of 93.9% with the use of a cutoff value of 6.5 x 10 BKV VP1 mRNA copy number per nanogram of total RNA ( <0.00001). In the receiver operating characteristic curve analysis, the calculated area under the curve was 0.949 (95% confidence interval, 0.912 to 0.987, <0.00001) for BKV VP1 mRNA levels and 0.562 (95% confidence interval, 0.417 to 0.708, >0.2) for 18S rRNA., Conclusions: Measurement of BKV VP1 mRNA in urinary cells offers a noninvasive and accurate means of diagnosing BKV nephritis.
- Published
- 2002
- Full Text
- View/download PDF
49. Successful retransplantation after renal allograft loss to polyoma virus interstitial nephritis.
- Author
-
Poduval RD, Meehan SM, Woodle ES, Thistlethwaite JR, Haas M, Cronin DC, Vats A, and Josephson MA
- Subjects
- Adult, Female, Humans, Polymerase Chain Reaction, Polyomavirus Infections diagnosis, Reoperation, Transplantation, Homologous, Tumor Virus Infections diagnosis, BK Virus, Kidney Transplantation adverse effects, Nephritis, Interstitial complications, Polyomavirus Infections complications, Tumor Virus Infections complications
- Abstract
Background: Although polyoma virus infection is being increasingly recognized as a cause of renal allograft dysfunction and failure, the risk of polyoma recurrence in a subsequent transplant is unknown. We present the first reported case of successful retransplantation after polyoma virus-induced renal allograft loss., Case Report: A 40-year-old Caucasian woman received a cadaveric kidney transplant. Baseline immunosuppression included corticosteroids, mycophenolate mofetil, and tacrolimus. Her post-transplant clinical course was complicated by an early acute rejection episode on posttransplant day (PTD) 6, that warranted treatment with OKT3. A biopsy performed on PTD 154 to evaluate a rise in creatinine revealed polyoma virus interstitial nephritis. Despite reduction in immunosuppression, the renal function progressively worsened and dialysis was initiated by PTD 160, followed by transplant nephrectomy on PTD 184. Four months later, she received a living related kidney from her sister. Immunosuppression was initiated with prednisone, azathioprine, and tacrolimus. She had immediate graft function with a decrease in serum creatinine from 12.8 to 1.1 mg/dl. Three and one-half years after her second renal transplant, her allograft functions well, with a serum creatinine of 1 mg/dl. Both quantitative and qualitative assays of blood and urine (by PCR) remain negative for BK virus, indicating the absence of virus reactivation., Conclusion: Judicious retransplantation should be considered as a therapeutic option in the management of polyoma virus induced graft failure. Previous graft loss secondary to polyoma virus infection is not a contraindication to retransplantation.
- Published
- 2002
- Full Text
- View/download PDF
50. BK virus in solid organ transplant recipients: an emerging syndrome.
- Author
-
Mylonakis E, Goes N, Rubin RH, Cosimi AB, Colvin RB, and Fishman JA
- Subjects
- Humans, Polyomavirus Infections diagnosis, Polyomavirus Infections pathology, Tumor Virus Infections diagnosis, Tumor Virus Infections pathology, BK Virus, Organ Transplantation adverse effects, Polyomavirus Infections etiology, Tumor Virus Infections etiology
- Abstract
BK virus is a human polyomavirus associated with a range of clinical presentations from asymptomatic viruria with pyuria to ureteral ulceration with ureteral stenosis in renal transplant patients or hemorrhagic cystitis in bone marrow transplant recipients. Infection of renal allografts has been associated with diminished graft function in some individuals. Fortunately, however, the majority of patients with BK virus infections are asymptomatic. The type, duration, and intensity of immunosuppression are major contributors to susceptibility to the activation of BK virus infection. Histopathology is required for the demonstration of renal parenchymal involvement; urine cytology and viral polymerase chain reaction methods are useful adjunctive diagnostic tools. Current, treatment of immunosuppressed patients with polyomavirus viruria is largely supportive and directed toward minimizing immunosuppression. Improved diagnostic tools and antiviral therapies are needed for polyomavirus infections.
- Published
- 2001
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.