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      BK virus salivary shedding and viremia in renal transplant recipients

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          Abstract

          Objectives:

          This study aimed to verify the presence of polyomavirus BK (BKPyV) in the saliva of kidney transplant recipients and to correlate it with blood viremia.

          Material and Methods:

          We have conducted a cross-sectional study with a sample involving 126 renal transplant recipients. 126 samples of saliva and 52 samples of blood were collected from these patients. Detection and quantification of BKPyV were performed using a real-time PCR. To compare the presence of BKPyV in blood and saliva, the binomial proportion test was used. To verify associations between salivary shedding BKPyV and post-transplant periods (in months), the Mann-Whitney test was used. Spearman's correlation was used to correlate the viral load in the saliva with blood of kidney transplant recipients.

          Results:

          The mean age of the study group was 51.11±12.45 years old, and 69 participants (54.8%) were female, with a mean post-transplantation time of 4.80±6.04 months. BKPyV was quantified in several samples of saliva and blood, with medians of 1,108 cp/mL and 1,255 cp/mL, respectively. Only 16/52 (30.8%) participants presented BKPyV in blood, and 59/126 (46.8%) excreted the virus in saliva (p=0.004). BKPyV shedding was found in patients at a shorter post-transplantation period (3.86±5.25, p=0.100). A weak correlation was observed between viral quantification in saliva and blood (Spearman's correlation coefficient=0.193).

          Conclusion:

          The results of this study suggested that, although saliva excretes more BKPyV than blood, there is no reliable correlation between salivary shedding and blood viremia, showing two independent compartments of viral replication.

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          Most cited references21

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          Clinical and diagnostic utility of saliva as a non-invasive diagnostic fluid:
a systematic review

          This systematic review presents the latest trends in salivary research and its applications in health and disease. Among the large number of analytes present in saliva, many are affected by diverse physiological and pathological conditions. Further, the non-invasive, easy and cost-effective collection methods prompt an interest in evaluating its diagnostic or prognostic utility. Accumulating data over the past two decades indicates towards the possible utility of saliva to monitor overall health, diagnose and treat various oral or systemic disorders and drug monitoring. Advances in saliva based systems biology has also contributed towards identification of several biomarkers, development of diverse salivary diagnostic kits and other sensitive analytical techniques. However, its utilization should be carefully evaluated in relation to standardization of pre-analytical and analytical variables, such as collection and storage methods, analyte circadian variation, sample recovery, prevention of sample contamination and analytical procedures. In spite of all these challenges, there is an escalating evolution of knowledge with the use of this biological matrix.
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            Polyomavirus BK nephropathy: a (re-)emerging complication in renal transplantation.

            Persisting polyomavirus replication is now widely recognized as a (re-)emerging cause of renal allograft dysfunction. Up to 5% of renal allograft recipients can be affected about 40weeks (range 6-150) post-transplantation. Progression to irreversible failure of the allograft has been observed in up to 45% of all cases. The BK virus strain is involved in the majority of the cases. Risk factors may include treatment of rejection episodes and increasing viral replication under potent immunosuppressive drugs such as tacrolimus, sirolimus or mycophenolate. The diagnosis requires the histological demonstration of nuclear polyomavirus inclusions in affected tubular epithelial cells. Interstitial inflammatory infiltrates and fibrosis become more prominent in the persisting disease and may be difficult to distinguish from (coexisting) rejection. Detection of polyomavirus-inclusion bearing cells ('decoy cells') in the urine and quantification of BK virus DNA in the plasma have been proposed as surrogate markers for polyomavirus replication and allograft disease, respectively. Antiviral treatment is not yet established; however, reports of treatment with cidofovir are encouraging. Current management aims at the judicious modification and/or reduction of immunosuppression which, in view of preceding or concurrent rejection, is not without risk.
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              Real-time, quantitative PCR assays for the detection of virus-specific DNA in samples with mixed populations of polyomaviruses.

              Mixtures of polyomaviruses can be present in the central nervous system, the gastrointestinal tract, the genitourinary tract, blood, and urban sewage. We have developed 12 primer/probe sets (four per virus) for real-time, quantitative PCR assays (TaqMan) that can specifically detect BKV, JCV, and SV40 genomes present in mixtures of these viruses. The specificities of these primer/probe sets were determined by evaluating their level of interaction with the DNA from other polyomaviruses and their ability to estimate the number of copies of homologous viral DNA in blinded samples of defined mixtures of three polyomaviral DNAs. Three early region and three late region primer/probe sets determined, within a two-fold range, the number of copies of their respective DNAs. Four sets of SV40 primer/probes also detected 1.1-2.4 copies of SV40 DNA per COS-1 cell, cells estimated to contain a single copy of SV40 DNA. Three JCV primer/probe sets detected 3.7-4.2 copies per cell of JCV DNA in the JCV-transformed cell line M1-HR, cells estimated to contain between 0.5 and 1 copy of the JCV genome. We suggest that the virus-specific primer/probe sets in this study be considered sufficiently characterized to initiate the quantification of polyomavirus DNA in biological samples.
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                Author and article information

                Journal
                J Appl Oral Sci
                J Appl Oral Sci
                jaos
                Journal of Applied Oral Science
                Faculdade De Odontologia De Bauru - USP
                1678-7757
                1678-7765
                2019
                31 January 2019
                : 27
                : e20180435
                Affiliations
                [1 ]University of São Paulo, School of Dentistry, Stomatology Department, São Paulo, São Paulo, Brazil
                [2 ]University of São Paulo, Institute of Tropical Medicine of São Paulo, Laboratory of Virology, São Paulo, São Paulo, Brazil
                [3 ]University of São Paulo, Medical School, Hospital das Clínicas, Departament of Infectious and Parasitic Diseases, São Paulo, São Paulo, Brazil
                [4 ]University of São Paulo, Medical School, Hospital das Clínicas, Serviço de Transplante Renal, São Paulo, São Paulo, Brazil
                Author notes
                Corresponding address: Paulo Henrique Braz-Silva School of Dentristy - University of São Paulo - Av. Prof. Lineu Prestes, 2227 - Cidade Universitária - São Paulo - SP - Brasil. Phone: +5511 30917902 e-mail: pbraz@ 123456usp.br .
                Author information
                http://orcid.org/0000-0001-7972-9141
                http://orcid.org/0000-0002-0216-3028
                http://orcid.org/0000-0002-4526-4857
                http://orcid.org/0000-0001-6071-5110
                http://orcid.org/0000-0003-4181-3975
                http://orcid.org/0000-0002-1842-9521
                Article
                00425
                10.1590/1678-7757-2018-0435
                6438661
                30673031
                df9df29a-a5e9-4058-a1c3-3add9132f3cc

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 July 2018
                : 05 September 2018
                : 12 September 2018
                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 23
                Categories
                Original Article

                transplantation,bk virus,saliva,immunocompromised host,polymerase chain reaction

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