{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:12:02Z","timestamp":1760145122217,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["2016\/07892-2"],"award-info":[{"award-number":["2016\/07892-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. Methods: A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. Results: A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133\u2013595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. Conclusion: viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children.<\/jats:p>","DOI":"10.3390\/v16071017","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T10:10:07Z","timestamp":1719310207000},"page":"1017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of Herpesviridae Family Members, BK Virus, and Adenovirus in Children and Adolescents with Nephrotic Syndrome"],"prefix":"10.3390","volume":"16","author":[{"given":"Silvia Mendon\u00e7a","family":"Ferreira Menoni","sequence":"first","affiliation":[{"name":"Laboratory of Virology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas Lopes","family":"Leon","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9345-9931","authenticated-orcid":false,"given":"Rodrigo Gon\u00e7alves","family":"de Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Cristina Gerv\u00e1sio de Brito","family":"Lutaif","sequence":"additional","affiliation":[{"name":"Integrated Nephrology Center Unit, Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliane Cury","family":"Prates","sequence":"additional","affiliation":[{"name":"Integrated Nephrology Center Unit, Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian Monteiro Pereira","family":"Palma","sequence":"additional","affiliation":[{"name":"Integrated Nephrology Center Unit, Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra Cec\u00edlia Botelho","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera Maria Santoro","family":"Belangero","sequence":"additional","affiliation":[{"name":"Integrated Nephrology Center Unit, Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0630-5062","authenticated-orcid":false,"given":"Sandra Helena Alves","family":"Bonon","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, S\u00e3o Paulo 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(03)14184-0","article-title":"Nephrotic syndrome in childhood","volume":"362","author":"Eddy","year":"2003","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0140-6736(18)30536-1","article-title":"Idiopathic nephrotic syndrome in children","volume":"392","author":"Noone","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/S0140-6736(23)01051-6","article-title":"Childhood nephrotic syndrome","volume":"402","author":"Vivarelli","year":"2023","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1590\/2175-8239-jbn-2019-0001","article-title":"Incidence and risk factors for major infections in hospitalized children with nephrotic syndrome","volume":"41","author":"Kumar","year":"2019","journal-title":"J. Bras. Nefrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/ndt\/gfq574","article-title":"Glomerular diseases and transplantation: Similarities in pathogenetic mechanisms and treatment options","volume":"26","author":"Ponticelli","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1136\/ard.2008.100008","article-title":"Adverse events of low-to-medium-dose oral glucocorticoids in inflammatory diseases: A meta-analysis","volume":"68","author":"Hoes","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"623","DOI":"10.3851\/IMP2955","article-title":"Naturally occurring deletions\/insertions in HBV core promoter tend to decrease in hepatitis B e antigen-positive chronic hepatitis B patients during antiviral therapy","volume":"20","author":"Peng","year":"2015","journal-title":"Antivir. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.meegid.2017.10.023","article-title":"Novel HBV recombinants between genotypes B and C in 3\u2032-terminal reverse transcriptase (RT) sequences are associated with enhanced viral DNA load, higher RT point mutation rates and place of birth among Chinese patients","volume":"57","author":"Liu","year":"2018","journal-title":"Infect. Genet. Evol."},{"key":"ref_9","first-page":"853","article-title":"Nephropathy and viruses","volume":"1968","author":"Reimann","year":"2015","journal-title":"Postgrad. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1007\/s00467-015-3057-y","article-title":"Viral-associated glomerulopathies in children","volume":"30","author":"Wenderfer","year":"2015","journal-title":"Pediatr. Nephrol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jaci.2005.04.027","article-title":"Does early EBV infection protect against IgE sensitization?","volume":"116","author":"Nilsson","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1128\/CMR.00122-14","article-title":"Laboratory and clinical aspects of human herpesvirus 6 infections","volume":"28","author":"Agut","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1399-3038.1997.tb00150.x","article-title":"Correlation between Epstein Barr v\u00edrus antibodies, serum IgE, and atopic disease","volume":"8","author":"Calvani","year":"1997","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/1348-0421.12212","article-title":"The kinetics of urinary shedding of BK virus in children with renal disease","volume":"59","author":"Yamamoto","year":"2015","journal-title":"Microbiol. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"84","DOI":"10.5500\/wjt.v2.i6.84","article-title":"Polyomavirus-associated nephropathy","volume":"2","author":"Costa","year":"2012","journal-title":"World J. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S1473-3099(03)00770-9","article-title":"Polyomavirus BK","volume":"3","author":"Hirsch","year":"2003","journal-title":"Lancet Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/ajt.12110","article-title":"AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation","volume":"13","author":"Hirsch","year":"2013","journal-title":"Am. J. Transplant."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1556\/EuJMI.4.2014.1.2","article-title":"Human adenovirus: Viral pathogen with increasing importance","volume":"4","author":"Ghebremedhin","year":"2014","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/QCO.0000000000000451","article-title":"Human adenovirus infections: Update and consideration of mechanisms of viral persistence","volume":"31","author":"Radke","year":"2018","journal-title":"Curr. Opin. Infec. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/ajt.12112","article-title":"AST Infectious Diseases Community of Practice. Adenovirus in solid organ transplantation","volume":"13","author":"Florescu","year":"2013","journal-title":"Am. J. Transplant."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s10157-016-1267-7","article-title":"Pharmacokinetics of mycophenolic acid in children with clinically stable idiopathic nephrotic syndrome receiving cyclosporine","volume":"21","author":"Hibino","year":"2017","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"c179","DOI":"10.1159\/000339789","article-title":"KDIGO clinical practice guidelines for acute kidney injury","volume":"120","author":"Khwaja","year":"2012","journal-title":"Nephron Clin. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/S0022-3476(76)81125-0","article-title":"Plasma creatinine and urea concentration in children: Normal values for age and sex","volume":"88","author":"Schwartz","year":"1976","journal-title":"J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0022-3476(84)80479-5","article-title":"A simple estimate of glomerular filtration rate in full-term infants during the first year of life","volume":"104","author":"Schwartz","year":"1984","journal-title":"J. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/S0022-3476(85)80697-1","article-title":"A simple estimate of glomerular filtration rate in adolescent boys","volume":"106","author":"Schwartz","year":"1985","journal-title":"J. Pediatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1056\/NEJM197104082841406","article-title":"Recurrent Viral Infection (Reinfection)","volume":"284","author":"Chang","year":"1971","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/cid\/ciw668","article-title":"Definitions of Cytomegalovirus infection and disease in transplant patients for use in clinical trials","volume":"64","author":"Ljungman","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1002\/jmv.21534","article-title":"Prevalence of human papillomavirus and human herpes virus types 1\u20137 in human nasal polyposis","volume":"81","author":"Zaravinos","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/0140-6736(93)92814-A","article-title":"Epstein-Barr virus DNA in cerebrospinal fluid from patients with Aids-related primary lymphoma of the central nervous system","volume":"342","author":"Cinque","year":"1993","journal-title":"Lancet"},{"key":"ref_30","first-page":"679","article-title":"Association of detectable cytomegalovirus (CMV) DNA in monocytes rather than positive CMV IgG serology with elevated neopterin levels in community-dwelling older adults","volume":"46","author":"Leng","year":"2011","journal-title":"Exp. Gerontol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1182\/blood.V88.9.3615.bloodjournal8893615","article-title":"Lymphotropic herpesviruses in allogeneic bone marrow 7ransplantation","volume":"88","author":"Wang","year":"1996","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF01538827","article-title":"Human herpesvirus 6 and human herpesvirus 7 infections in kidney transplant recipients and healthy adults in Turkey","volume":"136","author":"Yalcin","year":"1994","journal-title":"Arch. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bjid.2019.01.005","article-title":"Polyomaviruses BK and JC DNA infection in peripheral blood cells from blood donors","volume":"23","author":"Haghighi","year":"2019","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0928-0197(98)00021-X","article-title":"Development and use of nested polymerase chain reaction (PCR) for the detection of adenovirus from conjunctivitis specimens","volume":"11","author":"Dalapathy","year":"1998","journal-title":"J. Clin. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1128\/jcm.26.12.2531-2535.1988","article-title":"The TH: Comparison between viremia and antigenemia for detection of cytomegalovirus in blood","volume":"26","author":"Schirm","year":"1988","journal-title":"J. Clin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/biomet\/73.1.13","article-title":"Longitudinal Data Analysis Using Generalized Linear Models","volume":"73","author":"Liang","year":"1986","journal-title":"Biometrika"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1007\/s00467-014-2860-1","article-title":"Prevalence of herpesviruses at onset of idiopathic nephrotic syndrome","volume":"29","author":"Dossier","year":"2014","journal-title":"Pediatr. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s11010-012-1406-8","article-title":"Response of VEGF to activation of viral receptors and TNFa in human mesangial cells","volume":"370","author":"Merkle","year":"2012","journal-title":"Mol. Cell Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13052-015-0123-9","article-title":"Steroid-sensitive nephrotic syndrome in children: Triggers of relapse and evolving hypotheses on pathogenesis","volume":"41","author":"Uwaezuoke","year":"2015","journal-title":"Ital. J. Pediatr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"535738","DOI":"10.1155\/2013\/535738","article-title":"Epstein-Barr virus in systemic autoimmune diseases","volume":"2013","author":"Draborg","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1097\/00007890-200109270-00006","article-title":"Patients at risk for development of posttransplant lymphoproliferative disorder: Plasma versus peripheral blood mononuclear cells as material for quantification of Epstein-Barr viral load by using real-time quantitative polymerase chain reaction","volume":"72","author":"Wagner","year":"2001","journal-title":"Transplantation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/00007890-199901150-00018","article-title":"Human polyoma virus-associated interstitial nephritis in the allograft kidney","volume":"67","author":"Randhawa","year":"1999","journal-title":"Transplantation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1097\/00007890-199903270-00022","article-title":"Polyomavirus disease under new immunosuppressive drugs","volume":"67","author":"Binet","year":"1999","journal-title":"Transplantation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/S0046-8177(99)90252-6","article-title":"Human polyoma virus in renal allograft biopsies: Morphological findings and correlation with urine cytology","volume":"30","author":"Drachenberg","year":"1999","journal-title":"Hum. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Boan, P., Hewison, C., Swaminathan, R., Irish, A., Warr, K., Sinniah, R., Pryce, T.M., and Flexman, J. (2016). Optimal use of plasma and urine BK viral loads for screening and predicting BK nephropathy. BMC Infect. Dis., 16.","DOI":"10.1186\/s12879-016-1652-6"},{"key":"ref_46","first-page":"7","article-title":"Cytomegalovirus and paediatric renal transplants: Is this a current issue?","volume":"33","year":"2013","journal-title":"Nefrologia"},{"key":"ref_47","first-page":"501","article-title":"Up to date of pathophysiology mechanism of idiopathic nephrotic syndromes: Minimal change disease and focal and segmental glomerulosclerosis","volume":"14","author":"Combe","year":"2018","journal-title":"N\u00e9phrol. Th\u00e9r."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jcv.2009.05.018","article-title":"Association of HHV-6 and HHV-7 reactivation with the development of chronic allograft nephropathy","volume":"46","author":"Chapenko","year":"2009","journal-title":"J. Clin. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40121-017-0180-z","article-title":"Who Is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific Evidence with a Focus on Hematopoietic Cell Transplant","volume":"7","author":"Styczynski","year":"2018","journal-title":"Infect. Dis. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1097\/01.inf.0000233542.48267.fd","article-title":"Adenoviral infections in pediatric transplant recipients: A hospital-based study","volume":"25","author":"Tellier","year":"2006","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/j.1651-2227.2012.02616.x","article-title":"Simultaneous presence of human herpesvirus 6 and adenovirus infections in intestinal intussusception of young children","volume":"1","author":"Lappalainen","year":"2012","journal-title":"Acta Paediatr."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/7\/1017\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:03:59Z","timestamp":1760108639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/7\/1017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,25]]},"references-count":51,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["v16071017"],"URL":"https:\/\/doi.org\/10.3390\/v16071017","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2024,6,25]]}}}