Efficacy of rituximab in refractory focal segmental glomerulosclerosis

Efficacy of rituximab in refractory focal segmental glomerulosclerosis | 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 Efficacy of rituximab in refractory focal segmental glomerulosclerosis Liangliang Chen, Xiaoli Lin, Xiaohan Huang, Yanhong Ma, Fanghao Cai, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7617059/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Nov, 2025 Read the published version in BMC Nephrology → Version 1 posted 12 You are reading this latest preprint version Abstract Objective: Refractory focal segmental glomerulosclerosis (FSGS) poses significant therapeutic challenges under conventional immunosuppressants. Although rituximab (RTX), an anti-CD20 monoclonal antibody, has demonstrated efficacy in nephrotic syndrome, its real-world effectiveness in adults with refractory FSGS remains unproven. Study Design: We retrospectively included 34 adults with biopsy-proven FSGS who remained refractory, defined by persistent proteinuria >3.5 g/day despite ≥4 months of corticosteroids/calcineurin inhibitors. Patients were grouped into either RTX combining with prednisone (RTX group, n = 16) or conventional non-RTX regimens (Conv group, n = 18). Rituximab was dosed to achieve peripheral B-cell depletion (CD19⁺ cell = 0/μL). Endpoints comprised complete remission (CR), overall response, relapse in initial responders, and relapse-free survival. Results: The patients were 44.4±21.8 years old, with a median follow-up duration of 18.0 (10.6, 41.1) months. The baseline characteristics were comparable between groups, except that RTX group had a longer disease duration than Conv group (median 10.7 vs. 4.0 months, p=0.046). The CR rate was 62.5% in RTX group and 33.3% in Conv group (p=0.168), while the overall response rate was 75.0% in RTX group and 50.0% in Conv-group (p=0.172). In patients who achieved initial overall response, RTX group had a lower relapse rate than Conv group (25.0% vs. 77.8%, p=0.030), and had a prolonged relapse-free survival (log-rank χ²=3.827, p=0.050). There were 3 patients in RTX group relapsed, who achieved CR after repeat RTX therapy. No severe infusion reactions or opportunistic infections were observed in RTX group. Conclusions: RTX combining with prednisone was comparable in inducing remission for refractory FSGS patients and better in relapse prevention than conventional therapy. While heterogeneity exists, RTX may be a valuable therapeutic strategy for maintaining long-term disease control in responsive patients. focal segmental glomerulosclerosis refractory rituximab remission relapse Figures Figure 1 Introduction Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage kidney disease (ESKD), characterized histologically by segmental scarring of glomeruli and clinically by proteinuria, hypoalbuminemia, and progressive renal dysfunction [ 1 ] . While conventional therapies such as corticosteroids and calcineurin inhibitors (CNI) remain first-line treatments, approximately 30–50% of patients exhibit steroid resistance or frequent relapses (termed "refractory FSGS") [ 2 ] . Long-term immunosuppressive therapy in these patients often leads to severe complications, including infections and metabolic disorders, highlighting the urgent need for safer and more effective therapeutic strategies. Rituximab (RTX), a monoclonal antibody targeting CD20 on B cells, has shown potential in pediatric nephrotic syndrome, including FSGS and minimal change disease (MCD) patients by depleting pathogenic B cells and reducing autoantibody production [ 3 – 6 ] . A systematic review and meta-analysis [ 7 ] synthesized data from three studies examining RTX treatment for frequently relapsing and steroid-dependent adult FSGS (a total of 17 cases), reporting a complete remission (CR) rate of 41%. Among these, one study included 8 FSGS patients treated exclusively with RTX, with only 1 patient showing a response to the treatment [ 8 ] . Another case report suggested that RTX combined with mycophenolate mofetil or CNIs may benefit some steroid-resistant FSGS patients [ 9 ] . However, the effect of RTX treatment for adult FSGS remains unclear. In a retrospective multicentered study, we included 81 adult patients with frequently relapsing or steroid dependent nephrotic syndrome with biopsy-proven MCD or FSGS, and found the relapse frequency, calculated as the ratio of relapse times to follow-up years, significantly decreased [0.04 (0.00, 0.08) vs. 1.71 (1.00, 2.45), p < 0.001] after rituximab therapy (cumulative 1393.8 ± 618.7 mg/ 2 years) during a 2-year follow-up; fifty-seven patients (70.4%) discontinued corticosteroids and immunosuppressants within 3 months after the first rituximab infusion [ 10 ] . In this study, we further evaluate the efficacy of RTX plus prednisone in treating refractory FSGS who were resist to prednisone or CNI in a single center. By integrating real-world evidence, we aim to provide experience for individualized therapeutic strategies for refractory FSGS. Patients and Methods Study Design and Population This retrospective cohort study included adult-onset patients with biopsy-confirmed refractory FSGS (including both new-onset and recurrent cases) who were treated at our center between October 2015 and June 2024. Refractory FSGS was defined as persistent proteinuria (> 3.5 g/day) with < 50% reduction from baseline after at least 4 months of prednisone or CNI according to the KDIGO 2021 Guideline [11]. All included patients had a minimum follow-up duration of 6 months. Patients were excluded if they met any of the following: 1). coexisting glomerular diseases (e.g., lupus nephritis, ANCA-associated vasculitis, IgA nephropathy, or membranous nephropathy) confirmed by biopsy or serological markers; 2). ESKD requiring maintenance dialysis for > 3 months at inclusion; 3). with family clustering of FSGS; 4). identifiable secondary causes. Treatment Protocol Treatment Protocol Following diagnosis of refractory disease, all patients converted to a multi-agent regimen combining two or more agents including prednisone, CNI, cyclophosphamide (CTX), tripterygium glycosides (TG) and RTX. Patients who received RTX combined with prednisone were classified into the RTX group. Patients treated with other immunosuppressants in combination without RTX were classified into the conventional therapy group (Conv group). The dosage of RTX was titrated according to circulating CD19 + B cell counts, in 2-week or 1-month interval until peripheral B cell depletion was reached. Peripheral B cell depletion was defined as the count of circulating CD19 + B cell reaching 0 cells/µL. Outcome Definitions Outcome Definitions Complete remission (CR) was defined as proteinuria < 0.3 g/day or urinary protein-to-creatinine ratio (uPCR) 35 g/L and stable serum creatinine. Partial remission (PR) was defined as a reduction in proteinuria to 0.3–3.5 g/day or uPCR 300–3500 mg/g, with a > 50% decrease from baseline and stable serum creatinine. Treatment response was defined as the composite of CR and PR. Relapse, which was assessed only in patients who achieved initial response with CR or PR, was characterized by either recurrence of nephrotic-range proteinuria (urinary protein > 3.5 g/day or uPCR > 3.5 g/g) after achieving CR or a > 50% increase in proteinuria during PR [ 11 ] . Data Collection and Statistical Analysis Clinical data, including demographics, laboratory parameters, and treatment details, were extracted from electronic medical records. Follow-up duration was defined as the time from the start of RTX or converted therapy to the last visit or dialysis dependence. Statistical analyses were performed using SPSS 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables are presented as mean ± standard deviation (normally distributed) or median [interquartile range (IQR)] (non-normal distribution), assessed by the Kolmogorov-Smirnov test. Group comparisons used Student’s t -test (normally distributed) or Mann-Whitney U test (non-normal distribution). Categorical variables were analyzed with χ² or Fisher’s exact test. Kaplan-Meier curves and log-rank tests evaluated relapse-free survival. A two-tailed p < 0.05 was considered statistically significant. Result A total of 34 patients with refractory FSGS were included (16 patients in the RTX group and 18 patients in the Conv group). The patients were 44.4 ± 21.8 years old, with a median follow-up of 18.0 (10.6, 41.1) months. The RTX group had a longer disease duration of 10.7 (5.4, 17.3) months compared to the Conv group of 4.0 (4.0, 6.4) months (p = 0.046). There were no significant differences in age, gender, comorbidities (hypertension, diabetes), BMI and laboratory parameters between groups. The albumin (21.3 ± 6.3 g/l vs 22.7 ± 6.7 g/l), creatinine [107.5 (81.8, 249.8) µmol/l vs 139.4 (87.8, 190.0) µmol/l] and uPCR [6.6 (5.9, 10.4) g/g vs 5.9 (3.3, 8.0) g/g] were comparable between the RTX group and the Conv group. The kidney pathology parameters including glomerular sclerosis [6.2 (2.8, 16.0) % vs 7.5 (0, 32.2) %], segmental sclerosis [0 (0, 3.8) % vs 0 (0, 8.3) %], and interstitial fibrosis [5.0 (5.0, 16.3) % vs 10.0 (3.8, 20.0) %] were also similar between the groups (Table 1 ). Table 1 Baseline characteristics of the Conv group and the RTX group Conv group RTX group Case, n 18 16 Age, years 49.0 ± 22.7 39.3 ± 20.2 0.200 Median follow-up time, months 15.8 (8.5, 35.4) 23.0 (12.0, 46.9) 0.583 Male/Female, n 16/2 11/5 0.214 Disease duration, months 4.0 (4.0, 6.4) 10.7 (5.4, 17.3) 0.046 Hypertension, n (%) 9 (50.0) 5 (37.5) 0.315 Diabetes, n (%) 2 (11.1) 1 (6.3) 0.999 BMI (kg/m 2 ) 24.3 ± 3.5 24.0 ± 3.2 0.858 Leukocyte counts, 10 9 /l 8.4 ± 2.8 9.1 ± 3.1 0.533 Hemoglobin, g/l 129.5 ± 24.5 140.6 ± 25.6 0.213 Platelets count, 10 9 /l 237.6 ± 96.5 283.4 ± 83.7 0.156 Albumin, g/l 22.7 ± 6.7 21.3 ± 6.3 0.540 Globulin, g/l 22.2 ± 5.6 19.5 ± 3.1 0.093 Creatinine, µmol/l 139.4 (87.8, 190.0) 107.5 (81.8, 249.8) 0.869 eGFR, ml/min/1.73m 2 58.5 (32.9, 78.3) 58.3 (25.0, 109.0) 0.680 Urinary protein creatinine ratio, g/g 5.9 (3.3, 8.0) 6.6 (5.9, 10.4) 0.257 Initial treatment, n (%) P/CNI/P + CNI/P + CTX/P + CNI + CTX 6/2/3/7/0 4/0/5/3/4 0.078 RAASi, n (%) 10 (55.6) 5 (37.5) 0.185 Converted immunotherapy regimens CNI + TG/P + CNI/P + CNI + TG/P + CTX 1/10/2/5 P + RTX / Renal biopsy Glomerular Sclerosis (%) 7.5 (0, 32.2) 6.2 (2.8, 16.0) 0.926 Segmentally sclerosis (%) 0 (0, 8.3) 0 (0, 3.8) 0.935 Interstitial fibrosis (%) 10.0 (3.8, 20.0) 5.0 (5.0, 16.3) 0.566 Note: BMI, body mass index; eGFR, estimated glomerular filtration rate; P, prednisone; CNI, calcineurin inhibitor; CTX, cyclophosphamide; RAASi, renin-angiotensin-aldosterone system inhibitors; TG, tripterygium glycosides; RTX, rituximab. In the Conv group, initial treatment regimens comprised prednisone monotherapy (n = 6), CNI monotherapy (n = 2), prednisone plus CNI (n = 3), and prednisone plus CTX (n = 7). After conversion, six patients receiving prednisone monotherapy and one patient receiving CNI monotherapy converted to prednisone plus CNI. Three patients receiving prednisone plus CTX converted to prednisone plus CNI. One patient receiving prednisone plus CNI converted to prednisone plus CTX. One patient receiving CNI monotherapy and two patients receiving prednisone plus CNI added TG in combination. Four patients receiving prednisone plus CTX maintained the original treatment regimen to accumulate the dose of CTX. The patient details in the RTX group are presented in Table 2 . Regarding the initial treatment regimens, four patients were treated with prednisone alone, and the remaining patients underwent either dual or triple combination therapies. The dosage of RTX, ranging from 100 to 600 mg per pulse, was adjusted based on circulating CD19 + B cell counts. Table 2 Detailed patient information in the RTX group Baseline Follow-up Relapse Last follow-up ID Gender Age (years) Treatment Disease duration (month) Urinary protein creatinine ratio, g/g Albumin (g/l) eGFR, ml/min/1.73m 2 Dose of RTX Duration of prednisone (month) Follow-up time (month) Treatment response Time to response(month) CR Relapse First Relapse time (month) Frequency Urinary protein creatinine ratio, g/g Albumin (g/l) eGFR, ml/min/1.73m 2 1 Female 18 P + CNI 5.0 3.9 27.4 122.4 5 cycles of 600 mg (q6-12month; total 3000 mg) 17.0 48.4 Yes 1.0 Yes No / / 0.04 43.8 101 2 Female 71 P 4.0 11.7 22.6 7.0 6 cycles of 200 mg (q1-3month; total 1200 mg) 12.0 12.0 Yes 1.0 Yes No / / 0.06 41.2 50.1 3 Male 35 P 9.4 4.5 27.3 109.2 600 mg ×2 (2-week interval) →700 mg (5th month) 4.0 14.0 Yes 6.0 Yes No / / 0.25 37.2 112 4 Female 53 P + CTX + CNI 14.9 22.2 32.4 59.0 1 dose of 600mg 3.0 18.0 Yes 1.0 Yes No / / 0.09 46.8 81.3 5 Male 19 P + CTX + CNI 7.0 6.6 24.2 22.4 600 mg ×2 (2-week interval) →600 mg q3-6month (total 3600 mg) 15.0 30.0 Yes 1.0 Yes No / / 0.13 48.4 126.2 6 Male 22 P + CNI 12.0 5.9 12.3 108.4 600 mg ×2 (2-week interval) →600 mg q6month (total 2400mg) 14.0 42.1 Yes 1.0 Yes No / / 0.03 44.4 121.5 7 Male 23 P + CTX 19.7 6.2 11.9 126.3 600 mg →400 mg at 1st month (2 doses total) 24.0 49.3 Yes 1.0 Yes No / / 0.13 49.4 121 8 Male 26 P + CNI 39.6 9.5 14.4 29.1 600 mg ×2 (2-week interval) →600 mg q17-19month (total 2400 mg) Continuous 40.8 Yes 1.0 Yes Yes 36.0 3 0.26 45.5 84 9 Male 22 P 12.0 5.0 19.5 131.3 600 mg ×2 (2-week interval) →repeated q6-12month (total 6000 mg) Continuous 64.9 Yes 3.0 Yes Yes 16.0 4 0.11 34.8 120.7 10 Male 21 P 5.3 6.6 17.8 105.5 600 mg ×2 (2-week interval) →repeated q8-10month (total 7200 mg) Continuous 79.2 Yes 1.0 Yes Yes 14.0 3 0.04 47.0 110 11 Male 59 P + CTX 4.0 12.9 22.8 23.6 600 mg ×2 (2-week interval) →100 mg×2 (3rd and 5th month) Continuous 28.0 Yes 1.0 No No / / 0.68 39.5 60.1 12 Male 62 P + CNI 12.0 6.0 22.0 46.5 300mg→200mg (1st month)→100mg q1-3month (total 1000mg) / 12.0 Yes 3.5 No No / / 1.15 44.4 83.6 13 Male 69 P + CTX + CNI 44.3 10.8 25.4 21.1 600 mg →500 mg after 2 weeks Continuous 6.0 No / No / / / 3.60 24.1 34.23 14 Male 51 P + CTX + CNI 7.5 6.5 12.4 39.4 500 mg ×2 (1-month interval) Continuous 6.0 No / No / / / 4.94 15.0 55.2 15 Female 58 P + CTX 5.7 6.0 28.6 61.7 100 mg monthly (total 1000mg) Continuous 10.0 No / No / / / 4.39 29.5 71.9 16 Female 20 P + CNI 18.0 7.1 19.9 57.2 300 mg ×2 (2-week interval) Continuous 16.5 No / No / / / 3.30 32.9 16.53 Note: eGFR, estimated glomerular filtration rate; CR, complete remission; P, prednisone; CNI, calcineurin inhibitor; CTX, cyclophosphamide; RTX, rituximab The treatment efficacy was showed in Table 3 . Six patients (33.3%) in the Conv group achieved CR, while 10 patients (62.5%) in the RTX group achieved CR (p = 0.168). The overall response rate was 50.0% (9/18) in Conv group and 75.0% (12/16) in RTX group (p = 0.172). In patients who achieved initial overall response, RTX group had a lower relapse rate than Conv group (25.0% vs. 77.8%, p = 0.03). There were 3 patients in RTX group relapsed, who achieved CR after repeat RTX therapy. Table 3 Outcomes between the Conv group and the RTX group Note: CR, complete remission; PR, partial remission Outcome Conv group RTX group P Case, No. 18 16 Median follow-up time, months 15.8 (8.5, 35.4) 23.0 (12.0, 46.9) 0.583 CR, No. (%) 6 (33.3) 10 (62.5) 0.168 Overall response (CR + PR), No. (%) 9 (50.0) 12 (75.0) 0.172 Time to response, month 2.4 (1.0, 6.0) 1.0 (1.0, 2.5) 0.173 Relapse among responders, No. (%) 7 (77.8) 3 (25.0) 0.030 Kaplan-Meier analysis of relapse-free survival in treatment-responsive patients demonstrated a clinically significant divergence between groups (Fig. 1 ). The log-rank test yielded a χ² value of 3.827 with a corresponding p-value of 0.05, indicating a statistically significant improvement in relapse free survival with RTX treatment at the conventional significance threshold. During the observation period, no severe acute adverse events were documented during or shortly after RTX administration. No hospitalization-requiring infections or opportunistic infections were reported within 3 months post-infusion. Transient mild-to-moderate infusion reactions (mild fever, chills) were observed in 3 patients (18.8%), resolving spontaneously without intervention. No severe infusion reactions were observed. Discussion This study demonstrated that RTX exhibited comparable short-term efficacy to conventional therapies in refractory FSGS, achieving similar CR and overall response rates, while conferring a significant advantage in relapse prevention. This dual benefit addresses a critical unmet need in FSGS management, where first-line agents (corticosteroids/CNIs) often fail to sustain remission despite initial efficacy [11]. The refractory FSGS cohort in our study was clinically characterized by abrupt-onset nephrotic syndrome with massive proteinuria—features strongly suggestive of primary FSGS based on established diagnostic criteria [ 11 , 12 – 14 ] . While formal subtyping was not performed retrospectively, the clinical phenotype aligns with primary FSGS. A prevailing hypothesis for primary FSGS pathogenesis involves circulating permeability factors that directly injure podocytes and disrupt the glomerular filtration barrier [ 15 , 16 ] . While the precise identity of these factors remains incompletely defined, potential candidates include soluble urokinase plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor 1 (CLC-1), and certain anti-podocyte autoantibodies [ 17 , 18 ] . These circulating factors are thought to originate, at least in part, from aberrant B-cell clones or plasma cells. Rituximab's efficacy in FSGS, as demonstrated in our study, can be mechanistically anchored in its potential to target the circulating factor pathway via profound B-cell depletion. This depletion also disrupts pathogenic B-cell/T-cell interactions that sustain glomerular inflammation and triggers widespread T cell compartment remodeling, such as changes in subset frequencies, activation states, and regulatory population expansion, ultimately reducing antigen presentation and inflammatory responses [ 19 ] . By eliminating CD20⁺ B cells, RTX directly reduces the source pool for pathogenic autoantibodies and potentially diminishes the production of other B-cell-derived soluble factors implicated in podocyte injury. A post-kidney transplantation study demonstrated that the combination of therapeutic plasma exchange and RTX significantly reduced suPAR level. The reduction in suPAR may serve as a potential biomarker for evaluating alterations in proteinuria and monitoring therapeutic response [ 20 ] . In addition, rituximab may exert a direct modulatory effect on podocytes through cross-reactivity with the SMPDL-3b protein and by regulating acid sphingomyelinase activity, which plays a critical role in lipid raft compartmentalization of the podocyte plasma membrane as well as in the structural organization and signaling pathways of podocytes [ 21 ] . However, the efficacy of RTX in treating FSGS remains heterogeneous. In our study, 25.0% of patients were unresponsive to RTX, and several prior studies have reported even higher rates of non-response to RTX treatment [ 8 , 22 , 23 ] . This variability in response to rituximab may be attributed to the underlying heterogeneity of FSGS, including genetic factors and variations in the susceptibility of podocytes or podocyte progenitors to injury. Chan et al. [ 24 ] identified prognostic markers that define a subset of FSGS patients with an immunologic signature indicating reduced T cell responsiveness, suggesting a better response to rituximab. Despite the heterogeneity in RTX efficacy for treating FSGS, our study demonstrated that RTX had a significant impact on reducing disease recurrence in patients who achieved an initial response, a finding consistent with previous research [ 25 , 26 ] . It has been reported that patients experiencing relapse during the post-rituximab follow-up period exhibited higher B-cell levels compared to those who remained in remission [ 26 ] . In our study, all three patients in the RTX group who experienced relapse showed B-cell reconstitution at the time of disease recurrence. Following retreatment with rituximab, B-cell depletion was reinduced, leading to a subsequent remission. However, not all responders with restored B-cells experienced disease relapse; Patient 4 and Patient 7 achieved long-term remission with just one or two doses of RTX. This might be attributed to the complete and durable elimination of the potential autoreactive clones. Such a mechanism aligns with the sustained remission observed following rituximab therapy in patients with idiopathic membranous nephropathy, where depletion of nephritogenic autoantibodies persists even after the reconstitution of circulating B lymphocytes [ 27 ] . Additional mechanisms involved interactions with T cells and direct effects on podocytes, as outlined in previous discussions. This study has several limitations that warrant consideration. First, its retrospective design inherently carried risks of selection bias and unmeasured confounding factors, despite efforts to match baseline characteristics. Second, the modest sample size limited statistical power for subgroup analyses and might obscure subtle efficacy differences. Third, heterogeneity in RTX dosing regimens and retreatment schedules complicated protocol standardization. While tailored dosing optimized B-cell depletion, it precluded definitive dose-response conclusions. Future prospective trials with protocolized dosing and extended surveillance are needed to address these gaps. Finally, the retrospective design is insufficient to evaluate long-term safety outcomes of RTX. Nevertheless, extensive prior studies across autoimmune diseases suggest generally favorable safety profiles for RTX, with severe adverse events being infrequent at standard doses supporting its acceptable risk-benefit ratio in this refractory population despite monitoring limitations. In conclusion, RTX demonstrated comparable short-term efficacy to conventional immunosuppressants, achieving similar rates of complete remission and overall response. Crucially, RTX significantly reduced relapse risk among responders and prolonged relapse-free survival, underscoring its role in sustaining remission. We advocate for individualized RTX integration into therapeutic sequences, guided by B-cell monitoring, while advocating for larger prospective studies to standardize protocols and validate predictive biomarkers. Declarations Ethics approval and consent to participate This study was conducted as per the Declaration of Helsinki and approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (No.[2025B]0222) and granted a waiver of informed consent. The requirement for consent was waived because the research involved only anonymised data extracted from medical records, and re-identification of participants was not possible. Data availability statements The datasets analysed during the current study are available from the corresponding author on reasonable request. Conflict of Interest All authors have no conflicts of interest to declare. Funding This study was funded by the National Natural Science Foundations of China (82400817, 82200782) to XH and YM, Young Scientist Project of Jiangxi Province (20243BBI91026) to PR. Author Contributions Research idea and study design: LC and FH. Data acquisition and patients’ follow up: LC, XL, XH, YM, FC, HZ, LL and PR. Supervision or mentorship: JC and FH. Draft manuscript: LC, and XL. Revision of manuscript: JW and FH. All authors reviewed the manuscript drafts, provided approval of the final version for submission, and took responsibility for the accuracy and integrity of the data. Acknowledgements Not applicable. Clinical Trail Number Not applicable. References References Vivette DD, Kaskel, Ronald J, Falk. Focal segmental glomerulosclerosis. N Engl J Med. 2011;365(25):2398–411. An SD, Vriese S, Sethi KA, Nath, et al. 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J] J Am Soc Nephrol. 2011;22(8):1543–50. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Nov, 2025 Read the published version in BMC Nephrology → Version 1 posted Editorial decision: Revision requested 03 Oct, 2025 Reviews received at journal 02 Oct, 2025 Reviews received at journal 02 Oct, 2025 Reviews received at journal 29 Sep, 2025 Reviewers agreed at journal 26 Sep, 2025 Reviewers agreed at journal 25 Sep, 2025 Reviewers agreed at journal 25 Sep, 2025 Reviewers invited by journal 25 Sep, 2025 Editor invited by journal 21 Sep, 2025 Editor assigned by journal 17 Sep, 2025 Submission checks completed at journal 17 Sep, 2025 First submitted to journal 15 Sep, 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. 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Lin","email":"","orcid":"","institution":"Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xiaoli","middleName":"","lastName":"Lin","suffix":""},{"id":524178826,"identity":"fc1357d0-32f1-40ed-bb78-36345c39f5e5","order_by":2,"name":"Xiaohan Huang","email":"","orcid":"","institution":"Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xiaohan","middleName":"","lastName":"Huang","suffix":""},{"id":524178827,"identity":"adb2e412-7283-419b-9d9f-0a55dc59d7c4","order_by":3,"name":"Yanhong Ma","email":"","orcid":"","institution":"Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of 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08:05:43","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":111988,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7617059/v1/b1c43bd86d03cf7f2c120a63.html"},{"id":93016398,"identity":"62462c51-92fa-4fa3-8525-0e0a807e48c7","added_by":"auto","created_at":"2025-10-08 08:05:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":12237,"visible":true,"origin":"","legend":"\u003cp\u003eRelapse-free survival of responsive patients. Log-rank=3.827, p=0.05\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7617059/v1/f780934a465c88f619cda3b0.png"},{"id":96650097,"identity":"587c5ae6-bcbd-45f5-be30-c5d6799d0a01","added_by":"auto","created_at":"2025-11-24 16:07:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":709582,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7617059/v1/661a933c-3e23-4ed8-b931-7adb4c8c5eca.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of rituximab in refractory focal segmental glomerulosclerosis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFocal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage kidney disease (ESKD), characterized histologically by segmental scarring of glomeruli and clinically by proteinuria, hypoalbuminemia, and progressive renal dysfunction \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. While conventional therapies such as corticosteroids and calcineurin inhibitors (CNI) remain first-line treatments, approximately 30\u0026ndash;50% of patients exhibit steroid resistance or frequent relapses (termed \"refractory FSGS\") \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Long-term immunosuppressive therapy in these patients often leads to severe complications, including infections and metabolic disorders, highlighting the urgent need for safer and more effective therapeutic strategies.\u003c/p\u003e\u003cp\u003eRituximab (RTX), a monoclonal antibody targeting CD20 on B cells, has shown potential in pediatric nephrotic syndrome, including FSGS and minimal change disease (MCD) patients by depleting pathogenic B cells and reducing autoantibody production \u003csup\u003e[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. A systematic review and meta-analysis \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e synthesized data from three studies examining RTX treatment for frequently relapsing and steroid-dependent adult FSGS (a total of 17 cases), reporting a complete remission (CR) rate of 41%. Among these, one study included 8 FSGS patients treated exclusively with RTX, with only 1 patient showing a response to the treatment \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Another case report suggested that RTX combined with mycophenolate mofetil or CNIs may benefit some steroid-resistant FSGS patients \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. However, the effect of RTX treatment for adult FSGS remains unclear.\u003c/p\u003e\u003cp\u003eIn a retrospective multicentered study, we included 81 adult patients with frequently relapsing or steroid dependent nephrotic syndrome with biopsy-proven MCD or FSGS, and found the relapse frequency, calculated as the ratio of relapse times to follow-up years, significantly decreased [0.04 (0.00, 0.08) vs. 1.71 (1.00, 2.45), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001] after rituximab therapy (cumulative 1393.8\u0026thinsp;\u0026plusmn;\u0026thinsp;618.7 mg/\u003csup\u003e2\u003c/sup\u003e years) during a 2-year follow-up; fifty-seven patients (70.4%) discontinued corticosteroids and immunosuppressants within 3 months after the first rituximab infusion \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. In this study, we further evaluate the efficacy of RTX plus prednisone in treating refractory FSGS who were resist to prednisone or CNI in a single center. By integrating real-world evidence, we aim to provide experience for individualized therapeutic strategies for refractory FSGS.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design and Population\u003c/h2\u003e\u003cp\u003eThis retrospective cohort study included adult-onset patients with biopsy-confirmed refractory FSGS (including both new-onset and recurrent cases) who were treated at our center between October 2015 and June 2024. Refractory FSGS was defined as persistent proteinuria (\u0026gt;\u0026thinsp;3.5 g/day) with \u0026lt;\u0026thinsp;50% reduction from baseline after at least 4 months of prednisone or CNI according to the KDIGO 2021 Guideline [11]. All included patients had a minimum follow-up duration of 6 months. Patients were excluded if they met any of the following: 1). coexisting glomerular diseases (e.g., lupus nephritis, ANCA-associated vasculitis, IgA nephropathy, or membranous nephropathy) confirmed by biopsy or serological markers; 2). ESKD requiring maintenance dialysis for \u0026gt;\u0026thinsp;3 months at inclusion; 3). with family clustering of FSGS; 4). identifiable secondary causes.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eTreatment Protocol\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eTreatment Protocol\u003c/div\u003e\u003cp\u003eFollowing diagnosis of refractory disease, all patients converted to a multi-agent regimen combining two or more agents including prednisone, CNI, cyclophosphamide (CTX), tripterygium glycosides (TG) and RTX. Patients who received RTX combined with prednisone were classified into the RTX group. Patients treated with other immunosuppressants in combination without RTX were classified into the conventional therapy group (Conv group). The dosage of RTX was titrated according to circulating CD19\u003csup\u003e+\u003c/sup\u003e B cell counts, in 2-week or 1-month interval until peripheral B cell depletion was reached. Peripheral B cell depletion was defined as the count of circulating CD19\u003csup\u003e+\u003c/sup\u003e B cell reaching 0 cells/\u0026micro;L.\u003c/p\u003e\n\u003ch3\u003eOutcome Definitions\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eOutcome Definitions\u003c/div\u003e\u003cp\u003eComplete remission (CR) was defined as proteinuria\u0026thinsp;\u0026lt;\u0026thinsp;0.3 g/day or urinary protein-to-creatinine ratio (uPCR)\u0026thinsp;\u0026lt;\u0026thinsp;300 mg/g, accompanied by serum albumin\u0026thinsp;\u0026gt;\u0026thinsp;35 g/L and stable serum creatinine. Partial remission (PR) was defined as a reduction in proteinuria to 0.3\u0026ndash;3.5 g/day or uPCR 300\u0026ndash;3500 mg/g, with a\u0026thinsp;\u0026gt;\u0026thinsp;50% decrease from baseline and stable serum creatinine. Treatment response was defined as the composite of CR and PR. Relapse, which was assessed only in patients who achieved initial response with CR or PR, was characterized by either recurrence of nephrotic-range proteinuria (urinary protein\u0026thinsp;\u0026gt;\u0026thinsp;3.5 g/day or uPCR\u0026thinsp;\u0026gt;\u0026thinsp;3.5 g/g) after achieving CR or a\u0026thinsp;\u0026gt;\u0026thinsp;50% increase in proteinuria during PR \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003eData Collection and Statistical Analysis\u003c/h3\u003e\n\u003cp\u003eClinical data, including demographics, laboratory parameters, and treatment details, were extracted from electronic medical records. Follow-up duration was defined as the time from the start of RTX or converted therapy to the last visit or dialysis dependence.\u003c/p\u003e\u003cp\u003eStatistical analyses were performed using SPSS 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (normally distributed) or median [interquartile range (IQR)] (non-normal distribution), assessed by the Kolmogorov-Smirnov test. Group comparisons used Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test (normally distributed) or Mann-Whitney \u003cem\u003eU\u003c/em\u003e test (non-normal distribution). Categorical variables were analyzed with χ\u0026sup2; or Fisher\u0026rsquo;s exact test. Kaplan-Meier curves and log-rank tests evaluated relapse-free survival. A two-tailed p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Result","content":"\u003cp\u003eA total of 34 patients with refractory FSGS were included (16 patients in the RTX group and 18 patients in the Conv group). The patients were 44.4\u0026thinsp;\u0026plusmn;\u0026thinsp;21.8 years old, with a median follow-up of 18.0 (10.6, 41.1) months. The RTX group had a longer disease duration of 10.7 (5.4, 17.3) months compared to the Conv group of 4.0 (4.0, 6.4) months (p\u0026thinsp;=\u0026thinsp;0.046). There were no significant differences in age, gender, comorbidities (hypertension, diabetes), BMI and laboratory parameters between groups. The albumin (21.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3 g/l vs 22.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7 g/l), creatinine [107.5 (81.8, 249.8) \u0026micro;mol/l vs 139.4 (87.8, 190.0) \u0026micro;mol/l] and uPCR [6.6 (5.9, 10.4) g/g vs 5.9 (3.3, 8.0) g/g] were comparable between the RTX group and the Conv group. The kidney pathology parameters including glomerular sclerosis [6.2 (2.8, 16.0) % vs 7.5 (0, 32.2) %], segmental sclerosis [0 (0, 3.8) % vs 0 (0, 8.3) %], and interstitial fibrosis [5.0 (5.0, 16.3) % vs 10.0 (3.8, 20.0) %] were also similar between the groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics of the Conv group and the RTX group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eConv group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e49.0\u0026thinsp;\u0026plusmn;\u0026thinsp;22.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.3\u0026thinsp;\u0026plusmn;\u0026thinsp;20.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.200\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian follow-up time, months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.8 (8.5, 35.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.0 (12.0, 46.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.583\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale/Female, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11/5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.214\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease duration, months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.0 (4.0, 6.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.7 (5.4, 17.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.046\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.315\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.999\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.858\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeukocyte counts, 10\u003csup\u003e9\u003c/sup\u003e/l\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.533\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin, g/l\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e129.5\u0026thinsp;\u0026plusmn;\u0026thinsp;24.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e140.6\u0026thinsp;\u0026plusmn;\u0026thinsp;25.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.213\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets count, 10\u003csup\u003e9\u003c/sup\u003e/l\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e237.6\u0026thinsp;\u0026plusmn;\u0026thinsp;96.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e283.4\u0026thinsp;\u0026plusmn;\u0026thinsp;83.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.156\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin, g/l\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.540\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlobulin, g/l\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.093\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine, \u0026micro;mol/l\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e139.4 (87.8, 190.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e107.5 (81.8, 249.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.869\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR, ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58.5 (32.9, 78.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58.3 (25.0, 109.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.680\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrinary protein creatinine ratio, g/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.9 (3.3, 8.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.6 (5.9, 10.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.257\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInitial treatment, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP/CNI/P\u0026thinsp;+\u0026thinsp;CNI/P\u0026thinsp;+\u0026thinsp;CTX/P\u0026thinsp;+\u0026thinsp;CNI\u0026thinsp;+\u0026thinsp;CTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6/2/3/7/0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4/0/5/3/4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.078\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRAASi, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (55.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.185\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConverted immunotherapy regimens\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCNI\u0026thinsp;+\u0026thinsp;TG/P\u0026thinsp;+\u0026thinsp;CNI/P\u0026thinsp;+\u0026thinsp;CNI\u0026thinsp;+\u0026thinsp;TG/P\u0026thinsp;+\u0026thinsp;CTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1/10/2/5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;RTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRenal biopsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlomerular Sclerosis (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.5 (0, 32.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.2 (2.8, 16.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.926\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSegmentally sclerosis (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0, 8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0, 3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.935\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInterstitial fibrosis (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.0 (3.8, 20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.0 (5.0, 16.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.566\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: BMI, body mass index; eGFR, estimated glomerular filtration rate; P, prednisone; CNI, calcineurin inhibitor; CTX, cyclophosphamide; RAASi, renin-angiotensin-aldosterone system inhibitors; TG, tripterygium glycosides; RTX, rituximab.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn the Conv group, initial treatment regimens comprised prednisone monotherapy (n\u0026thinsp;=\u0026thinsp;6), CNI monotherapy (n\u0026thinsp;=\u0026thinsp;2), prednisone plus CNI (n\u0026thinsp;=\u0026thinsp;3), and prednisone plus CTX (n\u0026thinsp;=\u0026thinsp;7). After conversion, six patients receiving prednisone monotherapy and one patient receiving CNI monotherapy converted to prednisone plus CNI. Three patients receiving prednisone plus CTX converted to prednisone plus CNI. One patient receiving prednisone plus CNI converted to prednisone plus CTX. One patient receiving CNI monotherapy and two patients receiving prednisone plus CNI added TG in combination. Four patients receiving prednisone plus CTX maintained the original treatment regimen to accumulate the dose of CTX.\u003c/p\u003e\u003cp\u003eThe patient details in the RTX group are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Regarding the initial treatment regimens, four patients were treated with prednisone alone, and the remaining patients underwent either dual or triple combination therapies. The dosage of RTX, ranging from 100 to 600 mg per pulse, was adjusted based on circulating CD19\u0026thinsp;+\u0026thinsp;B cell counts.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDetailed patient information in the RTX group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"20\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c19\" colnum=\"19\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c20\" colnum=\"20\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"7\" nameend=\"c15\" namest=\"c9\"\u003e\u003cp\u003eFollow-up\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c17\" namest=\"c16\"\u003e\u003cp\u003eRelapse\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c20\" namest=\"c18\"\u003e\u003cp\u003eLast follow-up\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eID\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDisease duration (month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eUrinary protein creatinine ratio, g/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eAlbumin (g/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eeGFR, ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDose of RTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eDuration of prednisone (month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eFollow-up time (month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTreatment response\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eTime to response(month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eRelapse\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eFirst Relapse time (month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eFrequency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eUrinary protein creatinine ratio, g/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003eAlbumin (g/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003eeGFR, ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CNI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e27.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e122.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5 cycles of 600 mg (q6-12month; total 3000 mg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e17.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e48.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e43.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e101\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e22.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e6 cycles of 200 mg (q1-3month; total 1200 mg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e12.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e12.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e41.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e50.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e27.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e109.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e600 mg \u0026times;2 (2-week interval) \u0026rarr;700 mg (5th month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e14.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e37.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e112\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CTX\u0026thinsp;+\u0026thinsp;CNI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e22.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e32.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e59.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1 dose of 600mg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e18.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e46.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e81.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CTX\u0026thinsp;+\u0026thinsp;CNI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e24.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e22.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e600 mg \u0026times;2 (2-week interval) \u0026rarr;600 mg q3-6month (total 3600 mg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e15.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e30.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e48.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e126.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CNI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e108.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e600 mg \u0026times;2 (2-week interval) \u0026rarr;600 mg q6month (total 2400mg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e14.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e42.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e44.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e121.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e19.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e126.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e600 mg \u0026rarr;400 mg at 1st month (2 doses total)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e24.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e49.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e49.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e121\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CNI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e39.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e14.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e29.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e600 mg \u0026times;2 (2-week interval) \u0026rarr;600 mg q17-19month (total 2400 mg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eContinuous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e40.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e36.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e45.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e19.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e131.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e600 mg \u0026times;2 (2-week interval) \u0026rarr;repeated q6-12month (total 6000 mg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eContinuous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e64.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e16.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e34.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e120.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e17.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e105.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e600 mg \u0026times;2 (2-week interval) \u0026rarr;repeated q8-10month (total 7200 mg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eContinuous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e79.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e14.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e47.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e110\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e22.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e23.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e600 mg \u0026times;2 (2-week interval) \u0026rarr;100 mg\u0026times;2 (3rd and 5th month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eContinuous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e28.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e0.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e39.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e60.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CNI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e22.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e46.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e300mg\u0026rarr;200mg (1st month)\u0026rarr;100mg q1-3month (total 1000mg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e12.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e1.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e44.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e83.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CTX\u0026thinsp;+\u0026thinsp;CNI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e44.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e25.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e21.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e600 mg \u0026rarr;500 mg after 2 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eContinuous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e3.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e24.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e34.23\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CTX\u0026thinsp;+\u0026thinsp;CNI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e39.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e500 mg \u0026times;2 (1-month interval)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eContinuous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e4.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e15.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e55.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e28.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e61.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e100 mg monthly (total 1000mg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eContinuous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e10.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e4.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e29.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e71.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u0026thinsp;+\u0026thinsp;CNI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e18.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e19.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e57.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e300 mg \u0026times;2 (2-week interval)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eContinuous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e16.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e3.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c19\"\u003e\u003cp\u003e32.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c20\"\u003e\u003cp\u003e16.53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"20\"\u003eNote: eGFR, estimated glomerular filtration rate; CR, complete remission; P, prednisone; CNI, calcineurin inhibitor; CTX, cyclophosphamide; RTX, rituximab\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe treatment efficacy was showed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Six patients (33.3%) in the Conv group achieved CR, while 10 patients (62.5%) in the RTX group achieved CR (p\u0026thinsp;=\u0026thinsp;0.168). The overall response rate was 50.0% (9/18) in Conv group and 75.0% (12/16) in RTX group (p\u0026thinsp;=\u0026thinsp;0.172). In patients who achieved initial overall response, RTX group had a lower relapse rate than Conv group (25.0% vs. 77.8%, p\u0026thinsp;=\u0026thinsp;0.03). There were 3 patients in RTX group relapsed, who achieved CR after repeat RTX therapy.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOutcomes between the Conv group and the RTX group Note: CR, complete remission; PR, partial remission\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eConv group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase, No.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian follow-up time, months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.8 (8.5, 35.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.0 (12.0, 46.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.583\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCR, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.168\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverall response (CR\u0026thinsp;+\u0026thinsp;PR), No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (75.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.172\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime to response, month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.4 (1.0, 6.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.0 (1.0, 2.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.173\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRelapse among responders, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (77.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.030\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eKaplan-Meier analysis of relapse-free survival in treatment-responsive patients demonstrated a clinically significant divergence between groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The log-rank test yielded a χ\u0026sup2; value of 3.827 with a corresponding p-value of 0.05, indicating a statistically significant improvement in relapse free survival with RTX treatment at the conventional significance threshold.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eDuring the observation period, no severe acute adverse events were documented during or shortly after RTX administration. No hospitalization-requiring infections or opportunistic infections were reported within 3 months post-infusion. Transient mild-to-moderate infusion reactions (mild fever, chills) were observed in 3 patients (18.8%), resolving spontaneously without intervention. No severe infusion reactions were observed.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that RTX exhibited comparable short-term efficacy to conventional therapies in refractory FSGS, achieving similar CR and overall response rates, while conferring a significant advantage in relapse prevention. This dual benefit addresses a critical unmet need in FSGS management, where first-line agents (corticosteroids/CNIs) often fail to sustain remission despite initial efficacy [11].\u003c/p\u003e\u003cp\u003eThe refractory FSGS cohort in our study was clinically characterized by abrupt-onset nephrotic syndrome with massive proteinuria\u0026mdash;features strongly suggestive of primary FSGS based on established diagnostic criteria \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. While formal subtyping was not performed retrospectively, the clinical phenotype aligns with primary FSGS. A prevailing hypothesis for primary FSGS pathogenesis involves circulating permeability factors that directly injure podocytes and disrupt the glomerular filtration barrier \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. While the precise identity of these factors remains incompletely defined, potential candidates include soluble urokinase plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor 1 (CLC-1), and certain anti-podocyte autoantibodies \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. These circulating factors are thought to originate, at least in part, from aberrant B-cell clones or plasma cells.\u003c/p\u003e\u003cp\u003eRituximab's efficacy in FSGS, as demonstrated in our study, can be mechanistically anchored in its potential to target the circulating factor pathway via profound B-cell depletion. This depletion also disrupts pathogenic B-cell/T-cell interactions that sustain glomerular inflammation and triggers widespread T cell compartment remodeling, such as changes in subset frequencies, activation states, and regulatory population expansion, ultimately reducing antigen presentation and inflammatory responses \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. By eliminating CD20⁺ B cells, RTX directly reduces the source pool for pathogenic autoantibodies and potentially diminishes the production of other B-cell-derived soluble factors implicated in podocyte injury. A post-kidney transplantation study demonstrated that the combination of therapeutic plasma exchange and RTX significantly reduced suPAR level. The reduction in suPAR may serve as a potential biomarker for evaluating alterations in proteinuria and monitoring therapeutic response \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. In addition, rituximab may exert a direct modulatory effect on podocytes through cross-reactivity with the SMPDL-3b protein and by regulating acid sphingomyelinase activity, which plays a critical role in lipid raft compartmentalization of the podocyte plasma membrane as well as in the structural organization and signaling pathways of podocytes \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eHowever, the efficacy of RTX in treating FSGS remains heterogeneous. In our study, 25.0% of patients were unresponsive to RTX, and several prior studies have reported even higher rates of non-response to RTX treatment \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. This variability in response to rituximab may be attributed to the underlying heterogeneity of FSGS, including genetic factors and variations in the susceptibility of podocytes or podocyte progenitors to injury. Chan \u003cem\u003eet al.\u003c/em\u003e \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e identified prognostic markers that define a subset of FSGS patients with an immunologic signature indicating reduced T cell responsiveness, suggesting a better response to rituximab.\u003c/p\u003e\u003cp\u003eDespite the heterogeneity in RTX efficacy for treating FSGS, our study demonstrated that RTX had a significant impact on reducing disease recurrence in patients who achieved an initial response, a finding consistent with previous research \u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. It has been reported that patients experiencing relapse during the post-rituximab follow-up period exhibited higher B-cell levels compared to those who remained in remission \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. In our study, all three patients in the RTX group who experienced relapse showed B-cell reconstitution at the time of disease recurrence. Following retreatment with rituximab, B-cell depletion was reinduced, leading to a subsequent remission. However, not all responders with restored B-cells experienced disease relapse; Patient 4 and Patient 7 achieved long-term remission with just one or two doses of RTX. This might be attributed to the complete and durable elimination of the potential autoreactive clones. Such a mechanism aligns with the sustained remission observed following rituximab therapy in patients with idiopathic membranous nephropathy, where depletion of nephritogenic autoantibodies persists even after the reconstitution of circulating B lymphocytes \u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. Additional mechanisms involved interactions with T cells and direct effects on podocytes, as outlined in previous discussions.\u003c/p\u003e\u003cp\u003eThis study has several limitations that warrant consideration. First, its retrospective design inherently carried risks of selection bias and unmeasured confounding factors, despite efforts to match baseline characteristics. Second, the modest sample size limited statistical power for subgroup analyses and might obscure subtle efficacy differences. Third, heterogeneity in RTX dosing regimens and retreatment schedules complicated protocol standardization. While tailored dosing optimized B-cell depletion, it precluded definitive dose-response conclusions. Future prospective trials with protocolized dosing and extended surveillance are needed to address these gaps. Finally, the retrospective design is insufficient to evaluate long-term safety outcomes of RTX. Nevertheless, extensive prior studies across autoimmune diseases suggest generally favorable safety profiles for RTX, with severe adverse events being infrequent at standard doses supporting its acceptable risk-benefit ratio in this refractory population despite monitoring limitations.\u003c/p\u003e\u003cp\u003eIn conclusion, RTX demonstrated comparable short-term efficacy to conventional immunosuppressants, achieving similar rates of complete remission and overall response. Crucially, RTX significantly reduced relapse risk among responders and prolonged relapse-free survival, underscoring its role in sustaining remission. We advocate for individualized RTX integration into therapeutic sequences, guided by B-cell monitoring, while advocating for larger prospective studies to standardize protocols and validate predictive biomarkers.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted as per the Declaration of Helsinki and approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (No.[2025B]0222) and granted a waiver of informed consent. The requirement for consent was waived because the research involved only anonymised data extracted from medical records, and re-identification of participants was not possible.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analysed during the current study are available from the corresponding author on reasonable request.\u003cbr\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the National Natural Science Foundations of China (82400817, 82200782) to XH and YM, Young Scientist Project of Jiangxi Province (20243BBI91026) to PR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearch idea and study design: LC and FH. Data acquisition and patients’ follow up: LC, XL, XH, YM, FC, HZ, LL and PR. Supervision or mentorship: JC and FH. Draft manuscript: LC, and XL. Revision of manuscript: JW and FH. All authors reviewed the manuscript drafts, provided approval of the final version for submission, and took responsibility for the accuracy and integrity of the data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trail Number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReferences\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eVivette DD, Kaskel, Ronald J, Falk. Focal segmental glomerulosclerosis. N Engl J Med. 2011;365(25):2398\u0026ndash;411.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAn SD, Vriese S, Sethi KA, Nath, et al. Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach. J Am Soc Nephrol. 2018;29(3):759\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChan Eugene Yu-Hin, Yu Ellen LM. Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study. J Am Soc Nephrol. 2022;33:1193\u0026ndash;207.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTan Liping L, Shaojun Y, Haiping, et al. Efficacy and acceptability of immunosuppressive agents for pediatric frequently-relapsing and steroid-dependent nephrotic syndrome: A network meta-analysis of randomized controlled trials. Med (Baltim). 2019;98:e15927.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJellouli Manel C, Rim M, Bayen, et al. Rituximab in The Management of Pediatric Steroid-Resistant Nephrotic Syndrome: A Systematic Review. J Pediatr. 2018;197:191\u0026ndash;e1971.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePietro Ravani R, Rossi A, Bonanni, et al. Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial. J Am Soc Nephrol. 2015;26(9):2259\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXue Cheng Y, Bo X, Jing, et al. Efficacy and safety of rituximab in adult frequent-relapsing or steroid-dependent minimal change disease or focal segmental glomerulosclerosis: a systematic review and meta-analysis. Clin Kidney J. 2020;14(4):1042\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRoccatello Dario S, Savino R, Daniela, et al. High-Dose Rituximab Ineffective for Focal Segmental Glomerulosclerosis: A Long-Term Observation Study. Am J Nephrol. 2017;46(2):108\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmbarsari CG, Saraswati M, Genta Syaifrin Laudza, Rituximab. Mycophenolic Acid, and Calcineurin Inhibitors Achieve Long-Term Remission in Pediatric Focal Segmental Glomerulosclerosis with Steroid-Resistant and Frequently Relapsing Nephrotic Syndrome: A Report of Two Cases. Case Rep Nephrol Dial. 2022;12(3):167\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLan Lan Y, Lin B, Yu, et al. 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.[J]. Am J Nephrol. 2023;55:25\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrad H, Rovin SG, Adler J, Barratt, et al. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100:S1\u0026ndash;276.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHommos Musab S, De Vriese An S, Alexander Mariam P, et al. The Incidence of Primary vs Secondary Focal Segmental Glomerulosclerosis: A Clinicopathologic Study. Mayo Clin Proc. 2017;92:1772\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePraga M, Morales E, Herrero JC, et al. Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration. Am J Kidney Dis. 1999;33:52\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShabaka A. Ana Tato Ribera, Gema Fern\u0026aacute;ndez-Ju\u0026aacute;rez. Focal Segmental Glomerulosclerosis: State-of-the-Art and Clinical Perspective.[J]. Nephron. 2020;144:0.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWei C, Hindi SE, Li J, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis.[J]. Nat Med. 2011;17(8):952\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJochen Reiser G, von Gersdorff M, Loos, et al. Induction of B7-1 in podocytes is associated with nephrotic syndrome.[J]. J Clin Invest. 2004;113(10):1390\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChangli W, Howard T, Jing, Li, et al. Circulating suPAR in two cohorts of primary FSGS.[J]. J Am Soc Nephrol. 2012;23:0.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEllen T, McCarthy M, Sharma, Virginia J, Savin. Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis.[J]. Clin J Am Soc Nephrol. 2010;5(11):2115\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiossis Stamatis-Nick C, Sfikakis Petros P. Rituximab-induced B cell depletion in autoimmune diseases: potential effects on T cells.[J]. Clin Immunol. 2008;127:280\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNada Alachkar JL, Matar D, et al. Monitoring suPAR levels in post-kidney transplant focal segmental glomerulosclerosis treated with therapeutic plasma exchange and rituximab.[J]. BMC Nephrol. 2018;19(1):361.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlessia Fornoni J, Sageshima C, Wei, et al. Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis.[J]. Sci Transl Med. 2011;3:0.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMagnasco A, Ravani P et al. Alberto, Edefonti,. Rituximab in children with resistant idiopathic nephrotic syndrome.[J]. J Am Soc Nephrol, 2012;23(6):1117-24.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGema F-F, Segarra A, Gonz\u0026aacute;lez E, et al. Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis.[J]. Clin J Am Soc Nephrol. 2009;4(8):1317\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChan C-Y, Liu ID, Resontoc LP, et al. T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS.[J]. Clin J Am Soc Nephrol. 2016;11(8):1360\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePhilipp Gauckler A, Matyjek S, Kapsia, et al. Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies[. J] J Am Soc Nephrol. 2025;36(4):668\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePiero Ruggenenti B, Ruggiero P, Cravedi, et al. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome.[J]. J Am Soc Nephrol. 2014;25(4):850\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLaurence H Jr, Beck FC, Fervenza DM, Beck, et al. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy[. J] J Am Soc Nephrol. 2011;22(8):1543\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":false,"isPdf":false,"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":"focal segmental glomerulosclerosis, refractory, rituximab, remission, relapse","lastPublishedDoi":"10.21203/rs.3.rs-7617059/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7617059/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e Refractory focal segmental glomerulosclerosis (FSGS) poses significant therapeutic challenges under conventional immunosuppressants. Although rituximab (RTX), an anti-CD20 monoclonal antibody, has demonstrated efficacy in nephrotic syndrome, its real-world effectiveness in adults with refractory FSGS remains unproven.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design:\u003c/strong\u003e We retrospectively included 34 adults with biopsy-proven FSGS who remained refractory, defined by persistent proteinuria \u0026gt;3.5 g/day despite ≥4 months of corticosteroids/calcineurin inhibitors. Patients were grouped into either RTX combining with prednisone (RTX group, n = 16) or conventional non-RTX regimens (Conv group, n = 18). Rituximab was dosed to achieve peripheral B-cell depletion (CD19⁺ cell = 0/μL). Endpoints comprised complete remission (CR), overall response, relapse in initial responders, and relapse-free survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The patients were 44.4±21.8 years old, with a median follow-up duration of 18.0 (10.6, 41.1) months. The baseline characteristics were comparable between groups, except that RTX group had a longer disease duration than Conv group (median 10.7 vs. 4.0 months, p=0.046). The CR rate was 62.5% in RTX group and 33.3% in Conv group (p=0.168), while the overall response rate was 75.0% in RTX group and 50.0% in Conv-group (p=0.172). In patients who achieved initial overall response, RTX group had a lower relapse rate than Conv group (25.0% vs. 77.8%, p=0.030), and had a prolonged relapse-free survival (log-rank χ²=3.827, p=0.050). There were 3 patients in RTX group relapsed, who achieved CR after repeat RTX therapy. No severe infusion reactions or opportunistic infections were observed in RTX group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e RTX combining with prednisone was comparable in inducing remission for refractory FSGS patients and better in relapse prevention than conventional therapy. While heterogeneity exists, RTX may be a valuable therapeutic strategy for maintaining long-term disease control in responsive patients.\u003c/p\u003e","manuscriptTitle":"Efficacy of rituximab in refractory focal segmental glomerulosclerosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-08 08:05:38","doi":"10.21203/rs.3.rs-7617059/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-03T09:23:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-02T14:48:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-02T12:55:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-29T10:59:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"71330850335922925644583836311801766698","date":"2025-09-26T12:58:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"16870295298886435718033929591525118380","date":"2025-09-25T13:46:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"138919704428104364400379955025827499927","date":"2025-09-25T07:20:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-25T06:57:01+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-22T03:47:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-17T11:30:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-17T11:30:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2025-09-15T06:44:32+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":"a6f5e22b-8813-4400-b99d-33f35b401e87","owner":[],"postedDate":"October 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-24T16:01:04+00:00","versionOfRecord":{"articleIdentity":"rs-7617059","link":"https://doi.org/10.1186/s12882-025-04580-8","journal":{"identity":"bmc-nephrology","isVorOnly":false,"title":"BMC Nephrology"},"publishedOn":"2025-11-18 15:57:32","publishedOnDateReadable":"November 18th, 2025"},"versionCreatedAt":"2025-10-08 08:05:38","video":"","vorDoi":"10.1186/s12882-025-04580-8","vorDoiUrl":"https://doi.org/10.1186/s12882-025-04580-8","workflowStages":[]},"version":"v1","identity":"rs-7617059","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7617059","identity":"rs-7617059","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}