Parental Perspectives on the Effectiveness and Safety of Rituximab in Treating Pediatric Nephrotic Syndrome: A Nationwide Multi-Center Survey Study

Parental Perspectives on the Effectiveness and Safety of Rituximab in Treating Pediatric Nephrotic Syndrome: A Nationwide Multi-Center Survey 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 Parental Perspectives on the Effectiveness and Safety of Rituximab in Treating Pediatric Nephrotic Syndrome: A Nationwide Multi-Center Survey Study Ning Lan, Chengguang Zhao, Li Wang, Hanyun Tang, Weiran Zhou, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6265885/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Jun, 2025 Read the published version in Pediatric Nephrology → Version 1 posted 5 You are reading this latest preprint version Abstract Background Rituximab is increasingly used for steroid-dependent/frequently relapsing nephrotic syndrome, yet parental perspectives on its real-world impact remain understudied. This study evaluated parental perceptions of rituximab’s effectiveness, safety, and socioeconomic effects. Methods A nationwide cross-sectional survey was conducted across eight pediatric centers in China (Feb 1–15, 2025). Validated questionnaires were administered to 570 parents of children with nephrotic syndrome, assessing rituximab efficacy, safety, financial burden, caregiver quality of life (SF-36), and treatment barriers. Multivariable regression models analyzed predictors of treatment satisfaction and parental well-being. Results Among 489 parents analyzed, 232 children (47.4%) received rituximab. Most parents (79.3%) reported good disease control, and 90.5% perceived overall improvement, with 10.3% achieving complete medication discontinuation. Regarding safety, 86.2% of parents observed no increase in respiratory infections, and 98.3% reported improved child quality of life. Financial burden influenced perceptions ; parents from households earning < $ 30,00 annually were less satisfied with rituximab efficacy (OR = 0.22, 95% CI: 0.08–0.60, P = 0.004). Higher SF-36 scores were reported by parents of children who discontinued steroids or had significant quality-of-life improvements. Immune suppression concerns (80.6%) and high costs remained major barriers. Conclusions This study demonstrates favorable parental perceptions of rituximab regarding efficacy, safety, and caregiver quality of life in pediatric nephrotic syndrome. However, financial toxicity and safety concerns limit its broader use. Policy interventions should prioritize financial subsidies, expand insurance coverage, and implement multidisciplinary support programs to address caregivers' psychosocial needs. Enhanced pre-treatment counseling and steroid-sparing protocols may further optimize parental satisfaction and treatment outcomes. Pediatric nephrotic syndrome Rituximab Parental perspectives Quality of life Health economics Treatment satisfaction Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Nephrotic syndrome (NS) is one of the most common chronic kidney diseases in children, characterized by severe proteinuria, hypoalbuminemia, hyperlipidemia, and pitting edema [ 1 ]. The incidence of NS varies by ethnicity, with a relatively higher prevalence among Asian children[ 2 ].The majority of cases are classified as idiopathic NS, with Minimal Change Disease (MCD) accounting for 80–90% of cases in children[ 3 ]. First-line corticosteroid therapy achieves remission in 80% of cases[ 4 ]; However, 50–60% develop steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing nephrotic syndrome (FRNS)[ 5 ], requiring prolonged steroid therapy, which increases the risk of growth retardation, hypertension, osteoporosis, and metabolic complications. For children with SDNS or FRNS, second-line immunosuppressive therapies such as calcineurin inhibitors (e.g., tacrolimus), mycophenolate mofetil (MMF), and alkylating agents (e.g., cyclophosphamide) are often employed. While these agents can reduce relapse rates and steroid dependency, they are associated with substantial side effects. Tacrolimus is linked to nephrotoxicity, hyperglycemia, and hypertension; MMF can cause gastrointestinal disturbances, leukopenia, and increased infection risk; and cyclophosphamide carries risks of gonadal toxicity, hemorrhagic cystitis, and long-term malignancy[ 6 ]. Furthermore, the high cost of these treatments places a significant financial burden on families, particularly in low and middle income countries, where access to these medications may be limited. The limitations of traditional treatments have led to an urgent need for safer and more effective treatment options. Rituximab (RTX), a monoclonal antibody targeting CD20-positive B cells[ 7 ], has been shown to reduce relapse rates and steroid dependency while minimizing the side effects associated with long-term corticosteroid and immunosuppressive use[ 4 ]. In Western countries, rituximab has been widely adopted and incorporated into treatment guidelines[ 3 ].In contrast, reports on RTX use in pediatric NS in China emerged relatively later[ 8 ].Despite its proven efficacy, RTX usage in China remains lower compared to Western countries, particularly in developing regions such as Western China, where economic constraints and limited medical knowledge create significant barriers to its adoption[ 9 ]. Many parents in these areas are hesitant to accept RTX due to misconceptions about its use as a cancer treatment, concerns about potential side effects (e.g., increased infection and malignancy risks), and the high cost of therapy[ 10 ]. The prolonged use of corticosteroids and immunosuppressants in managing NS places a substantial physical and psychological burden on parents[ 11 ], further complicating treatment decisions. Given these challenges, this study aims to evaluate parental perspectives on the effectiveness, safety, and financial implications of RTX in treating pediatric NS. Specifically, we seek to: Assess parental recognition and understanding of RTX as a treatment option for NS. Analyze parental satisfaction with RTX outcomes, including its efficacy and safety. Identify reasons for refusing RTX and summarize factors limiting its clinical application. Evaluate the impact of RTX on parents' quality of life using the SF-36 Quality of Life Survey[ 12 ]. By addressing these objectives, this study aims to provide evidence-based insights to guide the development of healthcare policies that improve access to RTX, reduce the physical and emotional burden on parents, and ultimately enhance treatment outcomes for children with NS. Materials and Methods Study Design This nationwide, multi-center, cross-sectional survey was conducted from February 1 to February 15, 2025, across eight medical centers in China, including the Children’s Hospital of Chongqing Medical University, Children's Hospital Affiliated to Shandong University, Children's Hospital of Guiyang, The First Affiliated Hospital of Xinjiang Medical University, Children’s Hospital of Soochow University,,Shengjing Hospital of China Medical University, The Second Xiangya Hospital of Central South University, and Chengdu Women and Children’s Medical Center. Parents of children diagnosed with nephrotic syndrome were invited to participate using a convenience sampling method. The study design is shown in Fig. 1 . Participants and Settings Convenience sampling was used to recruit parents of children diagnosed with SDNS or FRNS from eight hospitals across China. To ensure the accuracy and validity of the data, senior nephrologists from both outpatient and inpatient departments were involved in participant recruitment. These specialists provided one-on-one guidance to parents, explaining the purpose, significance, and instructions for completing the questionnaire. Parents were encouraged to ask questions during the process, and doctors were available to assist with any uncertainties. Participation was entirely voluntary, and parents could withdraw at any time without penalty. Participants completed a structured questionnaire covering ten sections (68 variables), including demographic information, caregiver recognition of RTX, treatment evaluation, and parents' health and emotional status. The SF-36 Quality of Life Survey was used to assess parents' health-related quality of life across eight dimensions: physical function, physical pain, general health, energy, social function, emotional function, and mental health. This rigorous approach ensured the scientific integrity and reliability of the data collection process. Exclusion criteria (1) incomplete or missing demographic/clinical information; (2) inconsistent or contradictory answers; (3) insufficient engagement (e.g., unusually short completion times or lack of response variability); (4) unclear or ambiguous responses; and (5) non-eligible participants. Data Analysis Two researchers independently analyzed the questionnaires. Data were encoded in Excel and analyzed using SPSS version 27.0. Statistical tests, including Pearson’s Chi-squared test, Fisher’s exact test, Wilcoxon rank sum test, and logistic regression analysis, were used (significance set at p < 0.05). The analysis followed a systematic coding process, which included familiarization with the content, initial coding, theme identification, and final theme refinement. Legal and ethics considerations The study protocol was conducted according to the Declaration of Helsinki, and was approved by the Medical Ethics Committee of the Children’s Hospital of Chongqing Medical University (Approval No. (49), 2025). All parents gave their consents and voluntarily participated in the study. Results 1. Characteristics of the Study Population A total of 570 parents participated in the survey. After rigorous quality control excluding 81 responses (14.2%) due to incomplete data, inconsistencies, or insufficient engagement, 489 responses were retained for analysis. Among these, 232 children (47.4%) received RTX, while 257 (52.6%) did not. Demographic and clinical characteristics are summarized in Table 1 . The cohort was predominantly composed of mothers (79.6%), with 88.3% of respondents aged 30–50 years. Educational attainment was modest: 36.8% of mothers and 37.2% of fathers had completed middle school. Socioeconomically, 74.8% of families reported an annual income below $ 8,000, and the proportion of households with an annual income greater than $ 3000 in the rituximab group is higher (64.3% vs. 53.3%). Geographically, 73.6% of participants resided in western China, and nearly half (47.6%) lived in rural areas. Among the 489 children, 64.2% were male, and 64.0% were diagnosed before age 6. The majority (89.8%) had a disease duration exceeding one year, with 39.1% experiencing symptoms for over five years. Notably, children receiving RTX were more likely to have earlier disease onset (diagnosis age 5 years: 40.9% vs. 37.4%, P = 0.002), reflecting potential selection bias toward refractory cases. 2. Parental Perspectives on Rituximab: Efficacy, Safety Evaluation, Concerns, and Expectations 2.1 Clinical Outcomes and Parental Perceptions Among RTX-treated children, 79.3% reported good disease control after rituximab treatment, and 90.5% showed overall clinical improvement. Notably, 10.3% achieved complete medication discontinuation, highlighting RTX’s potential as a steroid-sparing therapy. 86.2% noted no increase in respiratory infections, and 98.3% reported improved child quality of life (QoL), with no severe infections documented. Despite high efficacy ratings (89.2% satisfaction), dissatisfaction stemmed primarily from financial strain (61.3%) and concerns about immune suppression (80.6%). Logistic regression revealed that families earning < $ 30,00 annually had significantly lower satisfaction with RTX (OR = 0.22, 95% CI:0.08–0.60, P = 0.004). These findings highlight the interplay between socioeconomic status and treatment acceptability (Table 2 ). 2.2 Unmet Needs and Policy Expectations Parents articulated multifaceted demands to optimize care: Clinical Support: 64.6% prioritized personalized treatment plans, while 40.9% emphasized clearer explanations of RTX’s risks and benefits. Psychosocial Resources: 33.1% requested social assistance channels, and 15.1% sought psychological support to manage caregiver stress. System-Level Advocacy: A majority (81.8%) urged national subsidies to alleviate costs, and 70.8% advocated for standardized RTX eligibility criteria to ensure equitable access. Notably, 44.2% called for enhanced public education to dispel misconceptions about RTX (e.g., its association with cancer therapy), and 28.8% desired broader availability of alternative biologics. These priorities, visualized in Fig. 2 , underscore the need for integrated strategies addressing clinical, economic, and psychosocial barriers to RTX adoption. 3. Impact of Rituximab on Parental Quality of Life (SF-36) Parents of children receiving rituximab (RTX) reported modest improvements in their own health-related quality of life. While the overall SF-36 scores were similar between RTX and non-RTX groups (80.4 vs. 77.9, P = 0.349), specific dimensions revealed critical differences: General Health: RTX-treated parents scored significantly higher (median: 60 vs. 60, P = 0.044) and rated their general health more positively (P = 0.015).Vitality: Although scores were comparable (65 vs. 60, P = 0.291), fewer RTX parents reported "poor" vitality (P = 0.049), suggesting reduced fatigue burden. No significant differences were observed in physical function, social engagement, emotional well-being, or mental health (P > 0.05). These findings indicate that RTX’s benefits for children may partially alleviate caregiver health concerns, particularly in general well-being, but broader psychosocial support remains essential. The detailed results are shown in Table 3 . 4. Factors Influencing Parental Decisions and Well-being 4.1 Drivers of RTX Treatment Choice Univariate logistic regression identified five factors significantly associated with RTX adoption: higher father’s education (P = 0.007), annual income > $ 3,000 (P = 0.016), urban residence (P = 0.031), earlier disease onset (P = 0.019), and longer disease duration (P = 0.002). These findings suggest socioeconomic status and disease severity jointly shape treatment preferences (Table 1 ). 4.2 Determinants of Parental Satisfaction Multivariable analysis revealed: Maternal Perspective : Mothers reported lower perceived QoL improvements than fathers (OR = 2.65, 95% CI:1.02–8.01, P = 0.031), aligning with heightened sensitivity to residual symptoms. Steroid Impact : Steroid-dependent regimens correlated with decreased perceived QoL improvements (OR = 4.69, 95% CI:2.00–12.27, P < 0.001), driven by corticosteroid-related side effects. Economic Burden : Low-income families (< $ 30,00/year) expressed lower efficacy satisfaction (OR = 0.22, 95% CI:0.08–0.60, P = 0.004), exacerbated by high out-of-pocket costs (Fig. 3 ). 4.3 Predictors of Caregiver Well-being (SF-36) Conventional Therapy Group : Lower income predicted poorer parental QoL (OR = 0.43, 95% CI:0.26–0.72, P < 0.001). RTX Group : Steroid-free regimens (OR = 0.27, 95% CI:0.14–0.52, P < 0.001) and perceived child QoL improvements (OR = 0.39, 95% CI:0.20–0.78, P = 0.004) enhanced caregiver well-being (Fig. 4 ). Discussion This study provides valuable insights into parental perspectives on RTX for pediatric NS, highlighting its clinical benefits as well as the socioeconomic and psychological challenges faced by parents. The results show that parents generally had a positive assessment of rituximab treatment, but also highlighted several important socioeconomic factors that influenced their treatment choices and evaluations of treatment outcomes. Rituximab’s efficacy and safety in treating pediatric nephrotic syndrome were highly recognized by the parents. The majority of parents reported that rituximab was effective in controlling the disease and improving their child’s quality of life. Parents' treatment choices were influenced by multiple factors, particularly the family’s economic status, residence location, and the parents' educational background. Rituximab is prescribed more frequently in Beijing, Shanghai and Guangdong than in rural provinces in western and central China[ 13 ]. This regional variation highlights the need for policy adjustments to ensure equitable access to effective treatment for pediatric nephrotic syndrome across the country. Many developed countries, such as Japan, the United States and some European countries, provide insurance for rituximab for the treatment of nephrotic syndrome in children[ 14 ], making it more accessible to patients, whereas in China, rituximab for the treatment of nephrotic syndrome in children is not covered by public health insurance[ 15 ]. In economically disadvantaged families, parents tended to have a more negative perception of rituximab’s effectiveness due to the financial burden associated with treatment. This finding is evident in our study, where parents from low-income families reported lower satisfaction with the treatment outcomes of rituximab, suggesting that in economically underdeveloped areas, medical costs can become a significant barrier to treatment choices and satisfaction. Policy makers should strengthen medical support for low-income families, particularly by improving access to high-cost medications like rituximab, to alleviate financial burdens and enhance overall treatment satisfaction and effectiveness. Parental evaluations of treatment outcomes were closely related to the treatment regimen and doctor-patient communication. The study found that parents of children on steroid-based regimens generally had lower satisfaction with treatment outcomes, which can be attributed to the side effects associated with corticosteroid use. Long-term corticosteroid use can negatively affect both the child’s health and the parents' expectations of treatment success. In contrast, parents of children treated with rituximab, particularly those not on corticosteroids, generally reported better treatment outcomes and significant improvements in their child’s quality of life. This result is consistent with other studies[ 16 , 17 ], which demonstrated that steroid-sparing treatment regimens can effectively reduce treatment side effects, thereby enhancing caregiver satisfaction. Therefore, treatment strategies should aim to minimize the use of corticosteroids and adopt safer and more effective treatment options, which can increase parental trust and satisfaction with the treatment. The study also highlighted that caregiver satisfaction was strongly influenced by the level of information provided by physicians before the initiation of rituximab treatment. parents who received detailed explanations about the treatment were more likely to perceive greater improvements in their child’s quality of life. This finding underscores the importance of doctor-patient communication, especially in the treatment of chronic diseases. Physicians should proactively provide comprehensive treatment information to help parents set realistic expectations, reducing anxiety and dissatisfaction caused by informational gaps. Conclusion RTX offers a promising steroid-sparing alternative for children with SDNS/FRNS, demonstrating significant efficacy, safety and improving caregiver QoL. However, high treatment costs and concerns about biological agents limit its widespread adoption. Future efforts should focus on expanding financial support, optimizing patient selection criteria, and improving pre-treatment counseling. Further longitudinal studies are needed to assess the long-term impact of RTX on disease progression and caregiver burden. Limitations This study’s findings may be influenced by recall bias inherent to self-reported questionnaires, particularly for subjective outcomes like quality of life. Additionally, the geographic focus on western rural China limits generalizability to urban or high-income populations. The cross-sectional design further restricts causal interpretation and assessment of long-term RTX impacts. Future longitudinal studies with diverse cohorts are needed to validate these insights and track evolving caregiver burdens. Data sharing statement The datasets generated and analyzed during this study are available from the corresponding author upon reasonable request. Due to privacy and ethical restrictions, raw data containing potentially identifiable patient information are not publicly accessible. Code availability Not applicable. Abbreviations NS Nephrotic syndrome SDNS Steroid-dependent nephrotic syndrome ( FRNS Frequently relapsing nephrotic syndrome RTX Rituximab Declarations Data sharing statement The datasets generated and analyzed during this study are available from the corresponding author upon reasonable request. Due to privacy and ethical restrictions, raw data containing potentially identifiable patient information are not publicly accessible. Code availability Not applicable. Acknowledgements We sincerely thank all participating families and the clinical staff at the eight study centers for their invaluable contributions. We also extend our heartfelt gratitude to Ximing Xu and Mengwei Ding from the Big Data Engineering Center of the Children's Hospital of Chongqing Medical University for their expertise and support in data analysis. Additionally, we acknowledge the National Clinical Research Center for Child Health and Disorders (Chongqing, China) for their technical assistance in data management. Funding This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author information Authors and Affiliations Department of Nephrology, Children’s Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing 400014, China Ning Lan, Gaofu Zhang Department of Pediatric Nephrology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China Chengguang Zhao Department of Nephrology, Chengdu Women’s and Children’s Central Hospital, Chengdu 610041, Sichuan, China Li Wang Department of Nephrology and Immunology, Children’s Hospital of Soochow University, Suzhou 215025, Jiangsu, China Hanyun Tang Department of Nephrology, Children’s Hospital Affiliated to Shandong University (Jinan Children’s Hospital), Jinan 250022, Shandong, China Weiran Zhou Department of Pediatrics, Ward 3, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, Xinjiang, China Hongtao Zhu Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China Xiaoyan Li Department of Nephrology, Maternal and Child Health Hospital of Guiyang (Children’s Hospital of Guiyang), Guiyang 550003, Guizhou, China Yuhong Li Big Data Center for Children's Medical Care, Children's Hospital of Chongqing Medical University, Chongqing 400014, China Ximing Xu Author Contributions Gaofu Zhang: Conceptualization, Funding acquisition, Project administration, Supervision, Validation, Writing – review & editing. Ning Lan: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Visualization, Writing–original draft. Ximing Xu: Data Processing and Statistical Analysis. Chengguang Zhao, Li Wang, Hanyun Tang, Weiran Zhou, Hongtao Zhu, Xiaoyan Li, Yuhong Li: Resources, Investigation, Data curation (patient recruitment and questionnaire guidance), Validation (single-center data collection) Corresponding author Gaofu Zhang, PhD Department of Nephrology, Children’s Hospital of Chongqing Medical University, No. 136 Zhongshan 2nd Road, Yuzhong District, Chongqing 400014, China Email: [email protected] Ethics Declarations Ethics approval The study protocol was conducted according to the Declaration of Helsinki, and was approved by the Medical Ethics Committee of the Children’s Hospital of Chongqing Medical University (Approval No. (49), 2025). Consent to participate All parents gave their consents and voluntarily participated in the study. Consent for publication Not applicable. Conflict of interest The authors declare no competing interests. Additional information Correspondence and requests for materials should be addressed to Ning Lan or Gaofu Zhang. References Webb NJA et al (2019) Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation. BMJ 365:l1800 Banh THM et al (2016) Ethnic Differences in Incidence and Outcomes of Childhood Nephrotic Syndrome. Clin J Am Soc Nephrol 11(10):1760–1768 Chan EY et al (2020) Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic syndrome have important effects on outcomes. Kidney Int 97(2):393–401 Iijima K et al (2014) Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 384(9950):1273–1281 Gulati A et al (2010) Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol 5(12):2207–2212 Rehan ST et al (2024) Meta-analysis on the efficacy and safety of rituximab versus tacrolimus for nephrotic syndrome in the paediatric age group. Clin Kidney J 17(1):sfad263 Ravani P et al (2015) Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial. J Am Soc Nephrol 26(9):2259–2266 Sun L et al (2014) Efficacy of rituximab therapy in children with refractory nephrotic syndrome: a prospective observational study in Shanghai. World J Pediatr 10(1):59–63 Iorember F et al (2018) Cost analysis on the use of rituximab and calcineurin inhibitors in children and adolescents with steroid-dependent nephrotic syndrome. Pediatr Nephrol 33(2):261–267 Tran CL et al (2020) Pediatric Immunization Practices in Nephrotic Syndrome: An Assessment of Provider and Parental Knowledge. Front Pediatr 8:619548 Basu B et al (2018) Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome: A Randomized Clinical Trial. JAMA Pediatr 172(8):757–764 Huang HM et al (2023) Depression in children with nephrotic syndrome related to parents' stress, quality of life, and depression. World J Pediatr 19(2):194–199 Lan L et al (2024) Efficacy of Rituximab for Minimal Change Disease and Focal Segmental Glomerulosclerosis with Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome in Adults: A Chinese Multicenter Retrospective Study. Am J Nephrol 55(1):25–36 Kallash M, Smoyer WE, Mahan JD (2019) Rituximab Use in the Management of Childhood Nephrotic Syndrome. Front Pediatr 7:178 Liu J et al (2022) Protocol for an open-label, single-arm, multicentre clinical study to evaluate the efficacy and safety of rituximab in the first episode of paediatric idiopathic nephrotic syndrome. BMJ Open 12(10):e064216 Deegens JK, Wetzels JF (2015) Therapy: Maintenance of steroid-free remission in nephrotic syndrome. Nat Rev Nephrol 11(10):569–570 Kari JA et al (2020) Rituximab versus cyclophosphamide as first steroid-sparing agent in childhood frequently relapsing and steroid-dependent nephrotic syndrome. Pediatr Nephrol 35(8):1445–1453 Tables Tables 1 to 3 are available in the Supplementary Files section. Supplementary Files Tables.docx dates.xlsx questionnaire.pdf Cite Share Download PDF Status: Published Journal Publication published 25 Jun, 2025 Read the published version in Pediatric Nephrology → Version 1 posted Editorial decision: Major Revisions Needed 09 Apr, 2025 Reviewers agreed at journal 21 Mar, 2025 Reviewers invited by journal 20 Mar, 2025 Editor assigned by journal 20 Mar, 2025 First submitted to journal 19 Mar, 2025 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. 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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-6265885","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":431697772,"identity":"7d95e3fa-8ddb-45a0-9b0e-693f5d33d25d","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":431697773,"identity":"bd11796a-bde8-40b2-982d-bd94e67f52b6","order_by":1,"name":"Chengguang Zhao","email":"","orcid":"","institution":"Shengjing Hospital of China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chengguang","middleName":"","lastName":"Zhao","suffix":""},{"id":431697774,"identity":"3b383359-6d55-4b93-bce5-3517e2cd7a5f","order_by":2,"name":"Li Wang","email":"","orcid":"","institution":"Chengdu Women and Children's Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Wang","suffix":""},{"id":431697775,"identity":"ee70e2b5-f264-4b46-96e4-5873d60b5980","order_by":3,"name":"Hanyun Tang","email":"","orcid":"","institution":"Children's Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Hanyun","middleName":"","lastName":"Tang","suffix":""},{"id":431697776,"identity":"682867b5-efe1-48b8-8bc9-abca8e12c2bf","order_by":4,"name":"Weiran Zhou","email":"","orcid":"","institution":"Qilu Children's Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Weiran","middleName":"","lastName":"Zhou","suffix":""},{"id":431697777,"identity":"c26c2550-b442-46c0-a4d8-409507a4c692","order_by":5,"name":"Hongtao Zhu","email":"","orcid":"","institution":"Xinjiang Medical University Affiliated First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hongtao","middleName":"","lastName":"Zhu","suffix":""},{"id":431697778,"identity":"502dd725-3c0e-4f35-b75c-a20bec750947","order_by":6,"name":"Xiaoyan Li","email":"","orcid":"","institution":"The Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyan","middleName":"","lastName":"Li","suffix":""},{"id":431697779,"identity":"7b893944-25ef-4543-971b-3d6438f16a00","order_by":7,"name":"Yuhong Li","email":"","orcid":"","institution":"Guiyang Children's Hospital: Guiyang Maternity and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuhong","middleName":"","lastName":"Li","suffix":""},{"id":431697780,"identity":"451242f6-11b6-4968-8189-6b5c20d169a0","order_by":8,"name":"Ximing Xu","email":"","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ximing","middleName":"","lastName":"Xu","suffix":""},{"id":431697781,"identity":"a76bc654-e130-492f-9a13-f9bf91e41978","order_by":9,"name":"Gaofu Zhang","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-4452-3674","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Gaofu","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-03-20 03:57:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6265885/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6265885/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00467-025-06862-7","type":"published","date":"2025-06-25T15:57:14+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79587433,"identity":"d6063b45-b6df-4134-9c11-a1cc9a1751a7","added_by":"auto","created_at":"2025-03-31 12:39:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":201060,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study design.\u003c/p\u003e\n\u003cp\u003eThis flowchart illustrates the study design, outlining the selection process of participants. The nationwide, multicenter cross-sectional survey was conducted in eight medical centers across China from February 1 to February 15, 2025. A total of 570 parents of children diagnosed with nephrotic syndrome (NS) were invited to participate using a convenience sampling method. After rigorous quality control, 81 responses (14.2%) were excluded due to incomplete data, inconsistencies, or insufficient engagement, leaving 489 valid responses for final analysis. Abbreviations: NS, nephrotic syndrome; RTX, rituximab.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-6265885/v1/d6f751cc0474520b54c6d4d6.png"},{"id":79589704,"identity":"5f365ccb-02e3-4648-8047-90889a1cc2da","added_by":"auto","created_at":"2025-03-31 12:55:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":26466,"visible":true,"origin":"","legend":"\u003cp\u003eNeeds of Parents of Children with Nephrotic Syndrome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e Needs of 489 parents of children with nephrotic syndrome for doctors and medical centers. \u003cstrong\u003eb\u003c/strong\u003eNeeds of 489 parents of children with nephrotic syndrome for health policymaking institutions and the national government. Abbreviation: RTX, rituximab.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6265885/v1/6e9ff41714f8648a91b5fd16.png"},{"id":79587435,"identity":"8842b997-0c91-4244-b67a-5554a07559bd","added_by":"auto","created_at":"2025-03-31 12:39:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":113817,"visible":true,"origin":"","legend":"\u003cp\u003eFactors influencing parental evaluation of QoL improvement and treatment efficacy after RTX.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e Forest plot of the factors influencing the QoL improvement by 232 parents of children with nephrotic syndrome who received RTX treatment.\u003cstrong\u003e b\u003c/strong\u003e Forest plot of the factors influencing the evaluation of treatment efficacy by 232 parents of children with nephrotic syndrome who received RTX treatment. Abbreviations: NS, nephrotic syndrome; RTX, rituximab; QoL, quality of life; GC, glucocorticoids; CI confidence interval.\u003c/p\u003e\n\u003cp\u003eMultivariable logistic regression was used to identify significant influencing factors, with statistical significance set at P \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6265885/v1/2680d4f0cea5d92141ebb52a.png"},{"id":79587437,"identity":"e650b9c0-8466-41b8-b7cd-139546ef39ed","added_by":"auto","created_at":"2025-03-31 12:39:32","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":83388,"visible":true,"origin":"","legend":"\u003cp\u003eFactors influencing SF-36 ratings in parents of children with NS\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e Forest plot of the factors influencing SF-36 ratings in parents of 257 children with nephrotic syndrome treated with conventional therapy. \u003cstrong\u003eb\u003c/strong\u003e Forest plot of the factors influencing SF-36 ratings in parents of 232 children with nephrotic syndrome treated with rituximab. Abbreviations: CI confidence interval; NS, nephrotic syndrome; GC, glucocorticoids.\u003c/p\u003e\n\u003cp\u003eA P-value less than 0.05 was considered statistically significant.\u003c/p\u003e\n\u003cp\u003eMultivariable ordinal logistic regression analysis was performed.\u003c/p\u003e\n\u003cp\u003eThe SF-36 total scores was classified into four ratings: Excellent (≥90), Good (70-89), Average (50-69), and Poor (\u0026lt;50).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6265885/v1/e23169bf701a4b594addf3e5.png"},{"id":85686254,"identity":"b1432f80-ed80-440d-adbc-d5ecb9185c57","added_by":"auto","created_at":"2025-06-30 16:05:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1280365,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6265885/v1/a1e05fe4-3b5d-45c0-a3ff-807721521bb6.pdf"},{"id":79587431,"identity":"f47ee86d-2076-4a16-aabc-2b042575e91a","added_by":"auto","created_at":"2025-03-31 12:39:32","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":39954,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-6265885/v1/ee48f169924711521c7702ff.docx"},{"id":79588237,"identity":"593fabeb-bb5e-479a-8f82-1ddf7d24fca0","added_by":"auto","created_at":"2025-03-31 12:47:32","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":216888,"visible":true,"origin":"","legend":"","description":"","filename":"dates.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6265885/v1/f4a9bf615e45eab650c387fd.xlsx"},{"id":79589706,"identity":"d4748a91-9bc8-44ea-adbb-fac5217d9bb1","added_by":"auto","created_at":"2025-03-31 12:55:32","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":457859,"visible":true,"origin":"","legend":"","description":"","filename":"questionnaire.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6265885/v1/00da3cc486ec2a4573f202d8.pdf"}],"financialInterests":"","formattedTitle":"Parental Perspectives on the Effectiveness and Safety of Rituximab in Treating Pediatric Nephrotic Syndrome: A Nationwide Multi-Center Survey Study","fulltext":[{"header":"Background","content":"\u003cp\u003eNephrotic syndrome (NS) is one of the most common chronic kidney diseases in children, characterized by severe proteinuria, hypoalbuminemia, hyperlipidemia, and pitting edema [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The incidence of NS varies by ethnicity, with a relatively higher prevalence among Asian children[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].The majority of cases are classified as idiopathic NS, with Minimal Change Disease (MCD) accounting for 80\u0026ndash;90% of cases in children[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. First-line corticosteroid therapy achieves remission in 80% of cases[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]; However, 50\u0026ndash;60% develop steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing nephrotic syndrome (FRNS)[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], requiring prolonged steroid therapy, which increases the risk of growth retardation, hypertension, osteoporosis, and metabolic complications.\u003c/p\u003e \u003cp\u003eFor children with SDNS or FRNS, second-line immunosuppressive therapies such as calcineurin inhibitors (e.g., tacrolimus), mycophenolate mofetil (MMF), and alkylating agents (e.g., cyclophosphamide) are often employed. While these agents can reduce relapse rates and steroid dependency, they are associated with substantial side effects. Tacrolimus is linked to nephrotoxicity, hyperglycemia, and hypertension; MMF can cause gastrointestinal disturbances, leukopenia, and increased infection risk; and cyclophosphamide carries risks of gonadal toxicity, hemorrhagic cystitis, and long-term malignancy[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Furthermore, the high cost of these treatments places a significant financial burden on families, particularly in low and middle income countries, where access to these medications may be limited.\u003c/p\u003e \u003cp\u003eThe limitations of traditional treatments have led to an urgent need for safer and more effective treatment options. Rituximab (RTX), a monoclonal antibody targeting CD20-positive B cells[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], has been shown to reduce relapse rates and steroid dependency while minimizing the side effects associated with long-term corticosteroid and immunosuppressive use[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In Western countries, rituximab has been widely adopted and incorporated into treatment guidelines[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].In contrast, reports on RTX use in pediatric NS in China emerged relatively later[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].Despite its proven efficacy, RTX usage in China remains lower compared to Western countries, particularly in developing regions such as Western China, where economic constraints and limited medical knowledge create significant barriers to its adoption[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Many parents in these areas are hesitant to accept RTX due to misconceptions about its use as a cancer treatment, concerns about potential side effects (e.g., increased infection and malignancy risks), and the high cost of therapy[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The prolonged use of corticosteroids and immunosuppressants in managing NS places a substantial physical and psychological burden on parents[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], further complicating treatment decisions.\u003c/p\u003e \u003cp\u003eGiven these challenges, this study aims to evaluate parental perspectives on the effectiveness, safety, and financial implications of RTX in treating pediatric NS. Specifically, we seek to: Assess parental recognition and understanding of RTX as a treatment option for NS. Analyze parental satisfaction with RTX outcomes, including its efficacy and safety. Identify reasons for refusing RTX and summarize factors limiting its clinical application. Evaluate the impact of RTX on parents' quality of life using the SF-36 Quality of Life Survey[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. By addressing these objectives, this study aims to provide evidence-based insights to guide the development of healthcare policies that improve access to RTX, reduce the physical and emotional burden on parents, and ultimately enhance treatment outcomes for children with NS.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis nationwide, multi-center, cross-sectional survey was conducted from February 1 to February 15, 2025, across eight medical centers in China, including the Children\u0026rsquo;s Hospital of Chongqing Medical University, Children's Hospital Affiliated to Shandong University, Children's Hospital of Guiyang, The First Affiliated Hospital of Xinjiang Medical University, Children\u0026rsquo;s Hospital of Soochow University,,Shengjing Hospital of China Medical University, The Second Xiangya Hospital of Central South University, and Chengdu Women and Children\u0026rsquo;s Medical Center. Parents of children diagnosed with nephrotic syndrome were invited to participate using a convenience sampling method. The study design is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants and Settings\u003c/h3\u003e\n\u003cp\u003eConvenience sampling was used to recruit parents of children diagnosed with SDNS or FRNS from eight hospitals across China. To ensure the accuracy and validity of the data, senior nephrologists from both outpatient and inpatient departments were involved in participant recruitment. These specialists provided one-on-one guidance to parents, explaining the purpose, significance, and instructions for completing the questionnaire. Parents were encouraged to ask questions during the process, and doctors were available to assist with any uncertainties. Participation was entirely voluntary, and parents could withdraw at any time without penalty.\u003c/p\u003e \u003cp\u003eParticipants completed a structured questionnaire covering ten sections (68 variables), including demographic information, caregiver recognition of RTX, treatment evaluation, and parents' health and emotional status. The SF-36 Quality of Life Survey was used to assess parents' health-related quality of life across eight dimensions: physical function, physical pain, general health, energy, social function, emotional function, and mental health. This rigorous approach ensured the scientific integrity and reliability of the data collection process.\u003c/p\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003cp\u003e(1) incomplete or missing demographic/clinical information; (2) inconsistent or contradictory answers; (3) insufficient engagement (e.g., unusually short completion times or lack of response variability); (4) unclear or ambiguous responses; and (5) non-eligible participants.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eTwo researchers independently analyzed the questionnaires. Data were encoded in Excel and analyzed using SPSS version 27.0. Statistical tests, including Pearson\u0026rsquo;s Chi-squared test, Fisher\u0026rsquo;s exact test, Wilcoxon rank sum test, and logistic regression analysis, were used (significance set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The analysis followed a systematic coding process, which included familiarization with the content, initial coding, theme identification, and final theme refinement.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eLegal and ethics considerations\u003c/h3\u003e\n\u003cp\u003e The study protocol was conducted according to the Declaration of Helsinki, and was approved by the Medical Ethics Committee of the Children\u0026rsquo;s Hospital of Chongqing Medical University (Approval No. (49), 2025). All parents gave their consents and voluntarily participated in the study.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003e1. Characteristics of the Study Population\u003c/h2\u003e\n \u003cp\u003eA total of 570 parents participated in the survey. After rigorous quality control excluding 81 responses (14.2%) due to incomplete data, inconsistencies, or insufficient engagement, 489 responses were retained for analysis. Among these, 232 children (47.4%) received RTX, while 257 (52.6%) did not. Demographic and clinical characteristics are summarized in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The cohort was predominantly composed of mothers (79.6%), with 88.3% of respondents aged 30\u0026ndash;50 years. Educational attainment was modest: 36.8% of mothers and 37.2% of fathers had completed middle school. Socioeconomically, 74.8% of families reported an annual income below \u003cspan\u003e$\u003c/span\u003e8,000, and the proportion of households with an annual income greater than \u003cspan\u003e$\u003c/span\u003e3000 in the rituximab group is higher (64.3% vs. 53.3%). Geographically, 73.6% of participants resided in western China, and nearly half (47.6%) lived in rural areas. Among the 489 children, 64.2% were male, and 64.0% were diagnosed before age 6. The majority (89.8%) had a disease duration exceeding one year, with 39.1% experiencing symptoms for over five years. Notably, children receiving RTX were more likely to have earlier disease onset (diagnosis age\u0026thinsp;\u0026lt;\u0026thinsp;3 years: 36.6% vs. 26.4%, P\u0026thinsp;=\u0026thinsp;0.019) and longer disease duration (\u0026gt;\u0026thinsp;5 years: 40.9% vs. 37.4%, P\u0026thinsp;=\u0026thinsp;0.002), reflecting potential selection bias toward refractory cases.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Heading\"\u003e\u003cstrong\u003e2. Parental Perspectives on Rituximab: Efficacy, Safety Evaluation, Concerns, and Expectations\u003c/strong\u003e\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003e2.1 Clinical Outcomes and Parental Perceptions\u003c/h2\u003e\n \u003cp\u003eAmong RTX-treated children, 79.3% reported good disease control after rituximab treatment, and 90.5% showed overall clinical improvement. Notably, 10.3% achieved complete medication discontinuation, highlighting RTX\u0026rsquo;s potential as a steroid-sparing therapy.\u003c/p\u003e\n \u003cp\u003e86.2% noted no increase in respiratory infections, and 98.3% reported improved child quality of life (QoL), with no severe infections documented.\u003c/p\u003e\n \u003cp\u003eDespite high efficacy ratings (89.2% satisfaction), dissatisfaction stemmed primarily from financial strain (61.3%) and concerns about immune suppression (80.6%). Logistic regression revealed that families earning \u0026lt;\u003cspan\u003e$\u003c/span\u003e30,00 annually had significantly lower satisfaction with RTX (OR\u0026thinsp;=\u0026thinsp;0.22, 95% CI:0.08\u0026ndash;0.60, P\u0026thinsp;=\u0026thinsp;0.004). These findings highlight the interplay between socioeconomic status and treatment acceptability (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003e2.2 Unmet Needs and Policy Expectations\u003c/h2\u003e\n \u003cp\u003eParents articulated multifaceted demands to optimize care: Clinical Support: 64.6% prioritized personalized treatment plans, while 40.9% emphasized clearer explanations of RTX\u0026rsquo;s risks and benefits. Psychosocial Resources: 33.1% requested social assistance channels, and 15.1% sought psychological support to manage caregiver stress. System-Level Advocacy: A majority (81.8%) urged national subsidies to alleviate costs, and 70.8% advocated for standardized RTX eligibility criteria to ensure equitable access. Notably, 44.2% called for enhanced public education to dispel misconceptions about RTX (e.g., its association with cancer therapy), and 28.8% desired broader availability of alternative biologics. These priorities, visualized in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, underscore the need for integrated strategies addressing clinical, economic, and psychosocial barriers to RTX adoption.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003e3. Impact of Rituximab on Parental Quality of Life (SF-36)\u003c/h2\u003e\n \u003cp\u003eParents of children receiving rituximab (RTX) reported modest improvements in their own health-related quality of life. While the overall SF-36 scores were similar between RTX and non-RTX groups (80.4 vs. 77.9, P\u0026thinsp;=\u0026thinsp;0.349), specific dimensions revealed critical differences: General Health: RTX-treated parents scored significantly higher (median: 60 vs. 60, P\u0026thinsp;=\u0026thinsp;0.044) and rated their general health more positively (P\u0026thinsp;=\u0026thinsp;0.015).Vitality: Although scores were comparable (65 vs. 60, P\u0026thinsp;=\u0026thinsp;0.291), fewer RTX parents reported \u0026quot;poor\u0026quot; vitality (P\u0026thinsp;=\u0026thinsp;0.049), suggesting reduced fatigue burden.\u003c/p\u003e\n \u003cp\u003eNo significant differences were observed in physical function, social engagement, emotional well-being, or mental health (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). These findings indicate that RTX\u0026rsquo;s benefits for children may partially alleviate caregiver health concerns, particularly in general well-being, but broader psychosocial support remains essential. The detailed results are shown in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003e4. Factors Influencing Parental Decisions and Well-being\u003c/h2\u003e\n \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e\n \u003ch2\u003e4.1 Drivers of RTX Treatment Choice\u003c/h2\u003e\n \u003cp\u003eUnivariate logistic regression identified five factors significantly associated with RTX adoption: higher father\u0026rsquo;s education (P\u0026thinsp;=\u0026thinsp;0.007), annual income \u0026gt;\u003cspan\u003e$\u003c/span\u003e3,000 (P\u0026thinsp;=\u0026thinsp;0.016), urban residence (P\u0026thinsp;=\u0026thinsp;0.031), earlier disease onset (P\u0026thinsp;=\u0026thinsp;0.019), and longer disease duration (P\u0026thinsp;=\u0026thinsp;0.002). These findings suggest socioeconomic status and disease severity jointly shape treatment preferences (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003e4.2 Determinants of Parental Satisfaction\u003c/h2\u003e\n \u003cp\u003eMultivariable analysis revealed: \u003cstrong\u003eMaternal Perspective\u003c/strong\u003e: Mothers reported lower perceived QoL improvements than fathers (OR\u0026thinsp;=\u0026thinsp;2.65, 95% CI:1.02\u0026ndash;8.01, P\u0026thinsp;=\u0026thinsp;0.031), aligning with heightened sensitivity to residual symptoms. \u003cstrong\u003eSteroid Impact\u003c/strong\u003e: Steroid-dependent regimens correlated with decreased perceived QoL improvements (OR\u0026thinsp;=\u0026thinsp;4.69, 95% CI:2.00\u0026ndash;12.27, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), driven by corticosteroid-related side effects. \u003cstrong\u003eEconomic Burden\u003c/strong\u003e: Low-income families (\u0026lt;\u003cspan\u003e$\u003c/span\u003e30,00/year) expressed lower efficacy satisfaction (OR\u0026thinsp;=\u0026thinsp;0.22, 95% CI:0.08\u0026ndash;0.60, P\u0026thinsp;=\u0026thinsp;0.004), exacerbated by high out-of-pocket costs (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003e4.3 Predictors of Caregiver Well-being (SF-36)\u003c/h2\u003e\n \u003cp\u003e\u003cstrong\u003eConventional Therapy Group\u003c/strong\u003e: Lower income predicted poorer parental QoL (OR\u0026thinsp;=\u0026thinsp;0.43, 95% CI:0.26\u0026ndash;0.72, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). \u003cstrong\u003eRTX Group\u003c/strong\u003e: Steroid-free regimens (OR\u0026thinsp;=\u0026thinsp;0.27, 95% CI:0.14\u0026ndash;0.52, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and perceived child QoL improvements (OR\u0026thinsp;=\u0026thinsp;0.39, 95% CI:0.20\u0026ndash;0.78, P\u0026thinsp;=\u0026thinsp;0.004) enhanced caregiver well-being (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e This study provides valuable insights into parental perspectives on RTX for pediatric NS, highlighting its clinical benefits as well as the socioeconomic and psychological challenges faced by parents. The results show that parents generally had a positive assessment of rituximab treatment, but also highlighted several important socioeconomic factors that influenced their treatment choices and evaluations of treatment outcomes.\u003c/p\u003e \u003cp\u003eRituximab\u0026rsquo;s efficacy and safety in treating pediatric nephrotic syndrome were highly recognized by the parents. The majority of parents reported that rituximab was effective in controlling the disease and improving their child\u0026rsquo;s quality of life. Parents' treatment choices were influenced by multiple factors, particularly the family\u0026rsquo;s economic status, residence location, and the parents' educational background. Rituximab is prescribed more frequently in Beijing, Shanghai and Guangdong than in rural provinces in western and central China[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This regional variation highlights the need for policy adjustments to ensure equitable access to effective treatment for pediatric nephrotic syndrome across the country. Many developed countries, such as Japan, the United States and some European countries, provide insurance for rituximab for the treatment of nephrotic syndrome in children[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], making it more accessible to patients, whereas in China, rituximab for the treatment of nephrotic syndrome in children is not covered by public health insurance[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In economically disadvantaged families, parents tended to have a more negative perception of rituximab\u0026rsquo;s effectiveness due to the financial burden associated with treatment. This finding is evident in our study, where parents from low-income families reported lower satisfaction with the treatment outcomes of rituximab, suggesting that in economically underdeveloped areas, medical costs can become a significant barrier to treatment choices and satisfaction.\u003c/p\u003e \u003cp\u003ePolicy makers should strengthen medical support for low-income families, particularly by improving access to high-cost medications like rituximab, to alleviate financial burdens and enhance overall treatment satisfaction and effectiveness.\u003c/p\u003e \u003cp\u003eParental evaluations of treatment outcomes were closely related to the treatment regimen and doctor-patient communication. The study found that parents of children on steroid-based regimens generally had lower satisfaction with treatment outcomes, which can be attributed to the side effects associated with corticosteroid use. Long-term corticosteroid use can negatively affect both the child\u0026rsquo;s health and the parents' expectations of treatment success. In contrast, parents of children treated with rituximab, particularly those not on corticosteroids, generally reported better treatment outcomes and significant improvements in their child\u0026rsquo;s quality of life. This result is consistent with other studies[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], which demonstrated that steroid-sparing treatment regimens can effectively reduce treatment side effects, thereby enhancing caregiver satisfaction. Therefore, treatment strategies should aim to minimize the use of corticosteroids and adopt safer and more effective treatment options, which can increase parental trust and satisfaction with the treatment.\u003c/p\u003e \u003cp\u003eThe study also highlighted that caregiver satisfaction was strongly influenced by the level of information provided by physicians before the initiation of rituximab treatment. parents who received detailed explanations about the treatment were more likely to perceive greater improvements in their child\u0026rsquo;s quality of life. This finding underscores the importance of doctor-patient communication, especially in the treatment of chronic diseases. Physicians should proactively provide comprehensive treatment information to help parents set realistic expectations, reducing anxiety and dissatisfaction caused by informational gaps.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eRTX offers a promising steroid-sparing alternative for children with SDNS/FRNS, demonstrating significant efficacy, safety and improving caregiver QoL. However, high treatment costs and concerns about biological agents limit its widespread adoption. Future efforts should focus on expanding financial support, optimizing patient selection criteria, and improving pre-treatment counseling. Further longitudinal studies are needed to assess the long-term impact of RTX on disease progression and caregiver burden.\u003c/p\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study\u0026rsquo;s findings may be influenced by recall bias inherent to self-reported questionnaires, particularly for subjective outcomes like quality of life. Additionally, the geographic focus on western rural China limits generalizability to urban or high-income populations. The cross-sectional design further restricts causal interpretation and assessment of long-term RTX impacts. Future longitudinal studies with diverse cohorts are needed to validate these insights and track evolving caregiver burdens.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eData sharing statement\u003c/h2\u003e \u003cp\u003eThe datasets generated and analyzed during this study are available from the corresponding author upon reasonable request. Due to privacy and ethical restrictions, raw data containing potentially identifiable patient information are not publicly accessible.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eCode availability\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNS Nephrotic syndrome\u003c/p\u003e\n\u003cp\u003eSDNS Steroid-dependent nephrotic syndrome (\u003c/p\u003e\n\u003cp\u003eFRNS Frequently relapsing nephrotic syndrome\u003c/p\u003e\n\u003cp\u003eRTX Rituximab\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData sharing statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during this study are available from the corresponding author upon reasonable request. Due to privacy and ethical restrictions, raw data containing potentially identifiable patient information are not publicly accessible.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely thank all participating families and the clinical staff at the eight study centers for their invaluable contributions. We also extend our heartfelt gratitude to Ximing Xu and Mengwei Ding from the Big Data Engineering Center of the Children\u0026apos;s Hospital of Chongqing Medical University for their expertise and support in data analysis. Additionally, we acknowledge the National Clinical Research Center for Child Health and Disorders (Chongqing, China) for their technical assistance in data management.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Nephrology, Children\u0026rsquo;s Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing 400014, China\u003c/p\u003e\n\u003cp\u003eNing Lan, Gaofu Zhang\u003c/p\u003e\n\u003cp\u003eDepartment of Pediatric Nephrology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China\u003c/p\u003e\n\u003cp\u003eChengguang Zhao\u003c/p\u003e\n\u003cp\u003eDepartment of Nephrology, Chengdu Women\u0026rsquo;s and Children\u0026rsquo;s Central Hospital, Chengdu 610041, Sichuan, China\u003c/p\u003e\n\u003cp\u003eLi Wang\u003c/p\u003e\n\u003cp\u003eDepartment of Nephrology and Immunology, Children\u0026rsquo;s Hospital of Soochow University, Suzhou 215025, Jiangsu, China\u003c/p\u003e\n\u003cp\u003eHanyun Tang\u003c/p\u003e\n\u003cp\u003eDepartment of Nephrology, Children\u0026rsquo;s Hospital Affiliated to Shandong University (Jinan Children\u0026rsquo;s Hospital), Jinan 250022, Shandong, China\u003c/p\u003e\n\u003cp\u003eWeiran Zhou\u003c/p\u003e\n\u003cp\u003eDepartment of Pediatrics, Ward 3, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, Xinjiang, China\u003c/p\u003e\n\u003cp\u003eHongtao Zhu\u003c/p\u003e\n\u003cp\u003eDepartment of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China\u003c/p\u003e\n\u003cp\u003eXiaoyan Li\u003c/p\u003e\n\u003cp\u003eDepartment of Nephrology, Maternal and Child Health Hospital of Guiyang (Children\u0026rsquo;s Hospital of Guiyang), Guiyang 550003, Guizhou, China\u003c/p\u003e\n\u003cp\u003eYuhong Li\u003c/p\u003e\n\u003cp\u003eBig Data Center for Children\u0026apos;s Medical Care, Children\u0026apos;s Hospital of Chongqing Medical University, Chongqing 400014, China\u003c/p\u003e\n\u003cp\u003eXiming Xu\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGaofu Zhang: Conceptualization, Funding acquisition, Project administration, Supervision, Validation, Writing\u0026nbsp;\u0026ndash;\u0026nbsp;review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003eNing Lan: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Visualization, Writing\u0026ndash;original draft.\u003c/p\u003e\n\u003cp\u003eXiming Xu: Data Processing and Statistical Analysis.\u003c/p\u003e\n\u003cp\u003eChengguang Zhao, Li Wang, Hanyun Tang, Weiran Zhou, Hongtao Zhu, Xiaoyan Li, Yuhong Li: Resources, Investigation, Data curation (patient recruitment and questionnaire guidance), Validation (single-center data collection)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGaofu Zhang, PhD\u003c/p\u003e\n\u003cp\u003eDepartment of Nephrology, Children\u0026rsquo;s Hospital of Chongqing Medical University,\u003c/p\u003e\n\u003cp\u003eNo. 136 Zhongshan 2nd Road, Yuzhong District, Chongqing 400014, China\u003c/p\u003e\n\u003cp\u003eEmail: [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was conducted according to the Declaration of Helsinki, and was approved by the Medical Ethics Committee of the Children\u0026rsquo;s Hospital of Chongqing Medical University (Approval No. (49), 2025).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll parents gave their consents and voluntarily participated in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence and requests for materials should be addressed to Ning Lan or Gaofu Zhang.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWebb NJA et al (2019) Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation. BMJ 365:l1800\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBanh THM et al (2016) Ethnic Differences in Incidence and Outcomes of Childhood Nephrotic Syndrome. Clin J Am Soc Nephrol 11(10):1760\u0026ndash;1768\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan EY et al (2020) Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic syndrome have important effects on outcomes. Kidney Int 97(2):393\u0026ndash;401\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIijima K et al (2014) Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 384(9950):1273\u0026ndash;1281\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGulati A et al (2010) Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol 5(12):2207\u0026ndash;2212\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRehan ST et al (2024) Meta-analysis on the efficacy and safety of rituximab versus tacrolimus for nephrotic syndrome in the paediatric age group. Clin Kidney J 17(1):sfad263\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRavani P et al (2015) Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial. J Am Soc Nephrol 26(9):2259\u0026ndash;2266\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun L et al (2014) Efficacy of rituximab therapy in children with refractory nephrotic syndrome: a prospective observational study in Shanghai. World J Pediatr 10(1):59\u0026ndash;63\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIorember F et al (2018) Cost analysis on the use of rituximab and calcineurin inhibitors in children and adolescents with steroid-dependent nephrotic syndrome. Pediatr Nephrol 33(2):261\u0026ndash;267\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTran CL et al (2020) Pediatric Immunization Practices in Nephrotic Syndrome: An Assessment of Provider and Parental Knowledge. Front Pediatr 8:619548\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBasu B et al (2018) Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome: A Randomized Clinical Trial. JAMA Pediatr 172(8):757\u0026ndash;764\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang HM et al (2023) Depression in children with nephrotic syndrome related to parents' stress, quality of life, and depression. World J Pediatr 19(2):194\u0026ndash;199\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLan L et al (2024) Efficacy of Rituximab for Minimal Change Disease and Focal Segmental Glomerulosclerosis with Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome in Adults: A Chinese Multicenter Retrospective Study. Am J Nephrol 55(1):25\u0026ndash;36\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKallash M, Smoyer WE, Mahan JD (2019) Rituximab Use in the Management of Childhood Nephrotic Syndrome. Front Pediatr 7:178\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu J et al (2022) Protocol for an open-label, single-arm, multicentre clinical study to evaluate the efficacy and safety of rituximab in the first episode of paediatric idiopathic nephrotic syndrome. BMJ Open 12(10):e064216\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeegens JK, Wetzels JF (2015) Therapy: Maintenance of steroid-free remission in nephrotic syndrome. Nat Rev Nephrol 11(10):569\u0026ndash;570\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKari JA et al (2020) Rituximab versus cyclophosphamide as first steroid-sparing agent in childhood frequently relapsing and steroid-dependent nephrotic syndrome. Pediatr Nephrol 35(8):1445\u0026ndash;1453\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pediatric nephrotic syndrome, Rituximab, Parental perspectives, Quality of life, Health economics, Treatment satisfaction","lastPublishedDoi":"10.21203/rs.3.rs-6265885/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6265885/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRituximab is increasingly used for steroid-dependent/frequently relapsing nephrotic syndrome, yet parental perspectives on its real-world impact remain understudied. This study evaluated parental perceptions of rituximab\u0026rsquo;s effectiveness, safety, and socioeconomic effects.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA nationwide cross-sectional survey was conducted across eight pediatric centers in China (Feb 1\u0026ndash;15, 2025). Validated questionnaires were administered to 570 parents of children with nephrotic syndrome, assessing rituximab efficacy, safety, financial burden, caregiver quality of life (SF-36), and treatment barriers. Multivariable regression models analyzed predictors of treatment satisfaction and parental well-being.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e Among 489 parents analyzed, 232 children (47.4%) received rituximab. Most parents (79.3%) reported good disease control, and 90.5% perceived overall improvement, with 10.3% achieving complete medication discontinuation. Regarding safety, 86.2% of parents observed no increase in respiratory infections, and 98.3% reported improved child quality of life. Financial burden influenced perceptions ; parents from households earning \u0026lt;\u003cspan\u003e$\u003c/span\u003e30,00 annually were less satisfied with rituximab efficacy (OR\u0026thinsp;=\u0026thinsp;0.22, 95% CI: 0.08\u0026ndash;0.60, P\u0026thinsp;=\u0026thinsp;0.004). Higher SF-36 scores were reported by parents of children who discontinued steroids or had significant quality-of-life improvements. Immune suppression concerns (80.6%) and high costs remained major barriers.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis study demonstrates favorable parental perceptions of rituximab regarding efficacy, safety, and caregiver quality of life in pediatric nephrotic syndrome. However, financial toxicity and safety concerns limit its broader use. Policy interventions should prioritize financial subsidies, expand insurance coverage, and implement multidisciplinary support programs to address caregivers' psychosocial needs. Enhanced pre-treatment counseling and steroid-sparing protocols may further optimize parental satisfaction and treatment outcomes.\u003c/p\u003e","manuscriptTitle":"Parental Perspectives on the Effectiveness and Safety of Rituximab in Treating Pediatric Nephrotic Syndrome: A Nationwide Multi-Center Survey Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 12:39:27","doi":"10.21203/rs.3.rs-6265885/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revisions Needed","date":"2025-04-09T11:34:49+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-03-21T14:19:44+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-20T16:31:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-20T16:04:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2025-03-19T23:56:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f01ab19a-5cb1-4947-b5c8-758b43243c05","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-30T16:03:37+00:00","versionOfRecord":{"articleIdentity":"rs-6265885","link":"https://doi.org/10.1007/s00467-025-06862-7","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2025-06-25 15:57:14","publishedOnDateReadable":"June 25th, 2025"},"versionCreatedAt":"2025-03-31 12:39:27","video":"","vorDoi":"10.1007/s00467-025-06862-7","vorDoiUrl":"https://doi.org/10.1007/s00467-025-06862-7","workflowStages":[]},"version":"v1","identity":"rs-6265885","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6265885","identity":"rs-6265885","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}