Latent Pathogen Reactivation During Six-Monthly Rituximab Therapy in Children with Idiopathic Nephrotic Syndrome: A Retrospective Cohort Study

Latent Pathogen Reactivation During Six-Monthly Rituximab Therapy in Children with Idiopathic Nephrotic Syndrome: A Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Latent Pathogen Reactivation During Six-Monthly Rituximab Therapy in Children with Idiopathic Nephrotic Syndrome: A Retrospective Cohort Study Ning Lan, Lu Tang, Jie Liu, Ximing Xu, Cong Liu, Gaofu Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8567341/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract Background Six-monthly rituximab therapy is increasingly used to maintain remission in children with idiopathic nephrotic syndrome. Data on infection safety, particularly patterns of latent pathogen reactivation, remain limited. Methods In this retrospective, self-controlled study, 110 children with idiopathic nephrotic syndrome received rituximab (375 mg/m²) every six months. Clinical and laboratory data were collected from 12 months before to 24 months after treatment. Infection events and pathogen status were independently adjudicated by infectious disease specialists. Results During follow-up, no cases of clinically overt Epstein–Barr virus, cytomegalovirus, hepatitis B virus, or tuberculosis infection were observed. Transient and clinically silent changes in latent infection markers occurred without progression to active disease. Two patients (1.8%) developed invasive fungal pneumonia caused by Pneumocystis jirovecii or Candida albicans , both in the setting of concomitant immunosuppressive therapy. Within 12 months after rituximab initiation, 22 children (20%) experienced common infections, predominantly involving the respiratory tract. The most frequently identified pathogens were Streptococcus pneumoniae and influenza virus. In exploratory multivariable analyses, female sex and steroid-resistant nephrotic syndrome were associated with a higher risk of infection. Rituximab-associated B-cell depletion and reductions in immunoglobulin G were reversible over time, and liver and kidney function remained stable. Conclusions In this single-center cohort, a fixed six-monthly rituximab regimen was not associated with clinically significant activation of latent viral or mycobacterial infections under systematic monitoring. Respiratory infections and invasive fungal disease, particularly in the presence of concomitant immunosuppression, remain important clinical considerations. Idiopathic nephrotic syndrome Rituximab Infection risk Latent infection Reactivation Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable1.pdf SupplementaryTable2.pdf SupplementaryTable3.pdf SupplementaryTable4.pdf SupplementaryTable5.pdf Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 11 Mar, 2026 Reviews received at journal 07 Mar, 2026 Reviews received at journal 04 Mar, 2026 Reviewers agreed at journal 20 Feb, 2026 Reviewers agreed at journal 20 Feb, 2026 Reviewers invited by journal 20 Feb, 2026 Editor invited by journal 18 Feb, 2026 Editor assigned by journal 14 Jan, 2026 Submission checks completed at journal 14 Jan, 2026 First submitted to journal 10 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8567341","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":595487500,"identity":"7a834c38-2f47-47b3-9610-0e4fdec4bb70","order_by":0,"name":"Ning Lan","email":"","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Lan","suffix":""},{"id":595487501,"identity":"fb51fb30-305e-4959-90ac-18198c9f588c","order_by":1,"name":"Lu Tang","email":"","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lu","middleName":"","lastName":"Tang","suffix":""},{"id":595487502,"identity":"4ab97c30-b2d6-43e5-af96-ce93dc3cd7d7","order_by":2,"name":"Jie Liu","email":"","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Liu","suffix":""},{"id":595487503,"identity":"7f3c90f3-f188-4ebd-8b27-9f30d19443bf","order_by":3,"name":"Ximing Xu","email":"","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ximing","middleName":"","lastName":"Xu","suffix":""},{"id":595487504,"identity":"662c1ade-d2d6-4c63-a1d5-514bbb566f9e","order_by":4,"name":"Cong Liu","email":"","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Cong","middleName":"","lastName":"Liu","suffix":""},{"id":595487507,"identity":"4e55da6a-d183-4ac6-a411-c996170b3981","order_by":5,"name":"Gaofu Zhang","email":"data:image/png;base64,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","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Gaofu","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2026-01-10 09:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8567341/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8567341/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103509932,"identity":"83f34f99-6158-4e24-836b-ce7691e102c3","added_by":"auto","created_at":"2026-02-26 14:02:13","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1161755,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8567341/v1_covered_77072f67-2c08-40e8-9771-4db7a1709325.pdf"},{"id":103353809,"identity":"7a4daf48-a9d2-4d50-a4db-cfe8332736aa","added_by":"auto","created_at":"2026-02-24 17:49:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":73119,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8567341/v1/7280e1eb40ed33835fc4455a.pdf"},{"id":103353813,"identity":"53a84d3b-7930-4166-9171-ebcdeb2040d4","added_by":"auto","created_at":"2026-02-24 17:49:09","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":80667,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8567341/v1/557fc72fed3700fbd19ca97d.pdf"},{"id":103507072,"identity":"5c5e82ba-c7a6-4239-be85-964fa372f8af","added_by":"auto","created_at":"2026-02-26 13:40:22","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":134973,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8567341/v1/a7c2aa484eac228234f10f43.pdf"},{"id":103353812,"identity":"f500f4e8-f8df-4595-a92f-e9bddc43b7ab","added_by":"auto","created_at":"2026-02-24 17:49:09","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":152098,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8567341/v1/5aad85b9c7c07946517f2bd9.pdf"},{"id":103353811,"identity":"dfd9a9ef-d544-4998-bec8-03e828b5cfba","added_by":"auto","created_at":"2026-02-24 17:49:09","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":112473,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8567341/v1/3b191fa37519f4a20ea0d2e9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Latent Pathogen Reactivation During Six-Monthly Rituximab Therapy in Children with Idiopathic Nephrotic Syndrome: A Retrospective Cohort Study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Idiopathic nephrotic syndrome, Rituximab, Infection risk, Latent infection, Reactivation","lastPublishedDoi":"10.21203/rs.3.rs-8567341/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8567341/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSix-monthly rituximab therapy is increasingly used to maintain remission in children with idiopathic nephrotic syndrome. Data on infection safety, particularly patterns of latent pathogen reactivation, remain limited.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this retrospective, self-controlled study, 110 children with idiopathic nephrotic syndrome received rituximab (375 mg/m\u0026sup2;) every six months. Clinical and laboratory data were collected from 12 months before to 24 months after treatment. Infection events and pathogen status were independently adjudicated by infectious disease specialists.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eDuring follow-up, no cases of clinically overt Epstein\u0026ndash;Barr virus, cytomegalovirus, hepatitis B virus, or tuberculosis infection were observed. Transient and clinically silent changes in latent infection markers occurred without progression to active disease. Two patients (1.8%) developed invasive fungal pneumonia caused by \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e or \u003cem\u003eCandida albicans\u003c/em\u003e, both in the setting of concomitant immunosuppressive therapy. Within 12 months after rituximab initiation, 22 children (20%) experienced common infections, predominantly involving the respiratory tract. The most frequently identified pathogens were \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e and influenza virus. In exploratory multivariable analyses, female sex and steroid-resistant nephrotic syndrome were associated with a higher risk of infection. Rituximab-associated B-cell depletion and reductions in immunoglobulin G were reversible over time, and liver and kidney function remained stable.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this single-center cohort, a fixed six-monthly rituximab regimen was not associated with clinically significant activation of latent viral or mycobacterial infections under systematic monitoring. Respiratory infections and invasive fungal disease, particularly in the presence of concomitant immunosuppression, remain important clinical considerations.\u003c/p\u003e","manuscriptTitle":"Latent Pathogen Reactivation During Six-Monthly Rituximab Therapy in Children with Idiopathic Nephrotic Syndrome: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-24 17:49:02","doi":"10.21203/rs.3.rs-8567341/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-11T19:31:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-08T03:34:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-04T20:31:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70468629079540469495663196047939988744","date":"2026-02-21T02:54:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"166258320066606847929055351994269769064","date":"2026-02-20T23:33:38+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-20T15:26:44+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-18T13:16:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-14T11:58:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-14T11:58:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2026-01-10T09:34:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f01ab19a-5cb1-4947-b5c8-758b43243c05","owner":[],"postedDate":"February 24th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-12T08:43:07+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-24 17:49:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8567341","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8567341","identity":"rs-8567341","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}