Efficacy of immunosuppressive therapy in low-risk and intermediate- risk idiopathic membranous nephropathy patients

Efficacy of immunosuppressive therapy in low-risk and intermediate- risk idiopathic membranous nephropathy patients | 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 immunosuppressive therapy in low-risk and intermediate- risk idiopathic membranous nephropathy patients Yan Jin, Yan Zhang, Lei Lan, Wei Chen, ChaoYi Chen, Jun Jiang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7696079/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The efficacy and safety of immunosuppressive therapy for low- and intermediate-risk idiopathic membranous nephropathy remains unclear. Method 121 renal biopsy-confirmed idiopathic membranous nephropathy (IMN) patients were retrospectively included from the Department of Nephrology in the First Affiliated Hospital of USTC from 2021 to 2023. Participants were stratified by baseline urinary protein-to-creatinine ratio (PCR) (low-risk group ≤ 3.0g/gCr v.s intermediate-risk group > 3.0g/gCr) and received immunosuppressive therapy at initial treatment. During a 12-month follow-up, proteinuria remission rates at 6 month and 12 month were compared between the two groups, and concurrently documented infectious events. Binary logistic regression analyze was conducted to identify the risk factors for proteinuria remission. Results During a 6-month follow-up, complete proteinuria remission rates in low-risk group was significantly higher than intermediate-risk group (62.1% v.s 41.8%, P = 0.03), but there were no significant difference on total proteinuria remission rates between low-risk group and intermediate-risk group (80.3% v.s 74.5%, P = 0.51). Binary logistic regression analyze showed that baseline serum albumin ( OR = 1.17, 95% CI :1.06–1.29, P < 0.01), glycemic abnormality ( OR = 0.32, 95% CI :0.12–0.86, P = 0.02), intermediate-risk group ( OR = 0.41, 95% CI : 0.19–0.99, P = 0.04), and hemoglobin as independent predictors for complete proteinuria remission at 6 month. During 12 months, total proteinuria remission rate (83.3% v.s 91.3%, P = 0.36) and complete proteinuria remission rate (75.0% v.s 65.2%, P = 0.29) had no significant difference between the two groups. Overall infection incidence was 7.4% (9/121), with no difference between the two groups, and no mortality events observed. Conclusion Immunosuppressive therapy increased the total and complete proteinuria remission rates of patients in low-risk group without increasing the risk of infection. Idiopathic membranous nephropathy Immunosuppressive Therapy Efficacy Infection Figures Figure 1 1. Introduction Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults and a significant contributor to end-stage renal disease (ESRD)[ 1 – 3 ]. Its pathogenesis is primarily associated with the deposition of immune complexes beneath the glomerular basement membrane podocytes, with anti-phospholipase A2 receptor (PLA2R) antibodies playing a key role in disease development[ 4 ].(Image 1) In terms of natural history, approximately 30% of IMN patients may progress to ESRD within 10–15 years, while about 30% achieve spontaneous remission. The remaining patients exhibit persistent proteinuria with relatively stable renal function[ 5 – 7 ]. Given the significant heterogeneity in clinical manifestations of IMN and the risks associated with immunosuppressive therapy—such as infections, metabolic disorders, and bone marrow suppression—both domestic and international guidelines emphasize the importance of risk-stratified treatment strategies. 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend supportive care and close monitoring for 6–12 months for low- and intermediate-risk patients, whereas high-risk patients with persistent nephrotic-range proteinuria (> 3.5 g/24 h) or ongoing renal function deterioration should initiate immunosuppressive therapy as early as possible[ 8 ]. The treatment goals for IMN include not only inducing proteinuria remission and delaying renal function progression but also improving patients' quality of life and minimizing treatment-related adverse events, such as infections, thromboembolic events, and cardiovascular complications[ 9 , 10 ]. Current clinical treatment options are diverse, including corticosteroids combined with alkylating agents, calcineurin inhibitors (such as tacrolimus and cyclosporine), biologics like rituximab, and novel targeted agents[ 6 , 11 ]. Among these regimens, immunosuppressive therapy is strongly recommended for patients with persistent severe proteinuria, as it may reduce the risk of disease relapse and help delay the progression to ESRD[ 12 ]. More than 30 years have passed since immunosuppressants were first used in the treatment of IMN[ 5 ], during which various immunosuppressive regimens have been proposed. Numerous studies have shown that, compared with supportive care alone, immunosuppressive therapy significantly improves proteinuria remission rates and slows the progression to ESRD[ 13 , 14 ]. However, the efficacy and safety of different treatment regimens require further investigation[ 15 ]. The use of immunosuppressants is a critical factor influencing clinical outcomes, yet comparative studies on the long-term efficacy of these drugs in large IMN patient cohorts are still limited. Therefore, this study aims to evaluate the impact of immunosuppressive agents on clinical outcomes in a cohort of IMN patients. This retrospective analysis included 121 IMN patients who received immunosuppressants as initial treatment. Based on baseline urine protein-to-creatinine ratio (PCR), patients were stratified into a low-risk group (PCR ≤ 3.0 g/g) and an intermediate-risk group (PCR > 3.0 g/g). Treatment efficacy and infection risk were assessed by comparing proteinuria remission rates and the incidence of infectious events between the two groups. 2. Methods 2.1. Data collection We retrospectively enrolled 121 patients with biopsy-confirmed IMN from the Nephrology Department of the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) between 2021 and 2023. The inclusion criteria comprised: (1) renal biopsy-confirmed IMN; (2) adult patients (aged ≥ 18 years); (3) no prior immunosuppressive therapy; (4) signed informed consent. Exclusion criteria included: (1) secondary MN (including but not limited to lupus-associated, hepatitis-related, drug/toxin-induced, or malignancy-associated forms); (2) any history of immunosuppressive therapy; (3) inadequate follow-up duration (<6 month); (4) estimated glomerular filtration rate (eGFR) < 30ml/min /1.73 m 2 . This study protocol adheres to the principles of the Declaration of Helsinki and complies with relevant Chinese clinical trial regulations and laws. It has been approved by the Medical Ethics Committee of the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) (Approval No.: 2025KY404). Written informed consent was obtained from all participants' guardians in accordance with the guiding principles of the Declaration of Helsinki. 2.2. Methods Using the hospital's database, we retrospectively collected the demographic information and clinical data, including: (1) Demographic characteristics: age, gender, and body mass index (BMI); (2) Laboratory parameters: urinary PCR, serum creatinine, eGFR, serum albumin (ALB), total cholesterol (TC), triglycerides (TG), hemoglobin, as well as binary variables indicating the presence or absence of dysglycemia and hypertension. Clinical outcomes and infection events were systematically documented. 2.3. Definitions eGFR was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Therapeutic responses were classified into three categories: (1) Partial remission (PR): ≥50% reduction in urinary PCR from baseline values; (2) Complete remission (CR): urinary PCR 35 g/l); (3) Treatment failure: inability to achieve either PR or CR criteria[ 8 , 10 ]. Total remission included partial remission and complete remission. 2.4. Statistical Analysis Statistical analyses were conducted by IBM SPSS Statistics (Version 26.0; IBM Corp., Armonk, NY, USA). Normally distributed continuous variables were described as mean ± standard deviation (SD) and compared by independent samples t -test. Non-normally distributed continuous variables were described as median (interquartile range, IQR) and compared by Mann-Whitney U test. Categorical variables were described as frequencies (percentages), between-group differences compared by Pearson's χ² or Fisher's exact test depending on expected counts. The primary efficacy endpoints included CR and total remission (CR + PR) rate. To identify independent predictors of proteinuria remission, Binary logistic regression analyses were performed adjusting for relevant covariates, with results reported as odds ratio ( OR ) and 95% confidence interval ( CI ). All statistical tests were two-tailed, with statistical significance defined as P < 0.05. 3. Results 3.1. Baseline characteristics of the 121 IMN patients The study comprised 121 biopsy-confirmed IMN patients, including 71 males (58.7%) and 50 females (41.3%). Baseline characteristics were as follows: age 52.0 [41.0–58.0] years, urinary PCR 2.8 [1.8, 4.3] g/g Cr, eGFR 116.3 [89.0, 138.1] ml/min/1.73m², and serum albumin 25.5 [22.0, 29.5] g/L. Based on baseline urinary PCR levels, risk stratification classified 66 patients (54.5%) as low-risk group and 55 patients (45.5%) as intermediate-risk group. Comparative analysis demonstrated statistically significant intergroup differences in TC, TG, eGFR, urinary PCR, and serum albumin levels (all P 0.05). (Table 1 ) Table 1 Baseline characteristics of the 121 IMN patients Variable All patients (n = 121) Low-risk group (n = 66) Intermediate-risk group (n = 55) P-value Age (year) 52.0 [41.0, 58.0] 51.5[39.0, 57.0] 52.0 [41.0, 60.0] 0.29 Sex [n(%)] Male 71.0 [58.7%] 37.0 [56.1%] 34.0 [61.8%] 0.58 Female 50.0 [41.3%] 29.0 [42.9%] 21.0 [38.2%] BMI (Kg/m 2 ) 24.5 [22.7, 27.1] 24.6 [22.6, 26.6] 24.2 [22.8, 27.5] 0.48 TC (mmol/l) 7.2 [5.8, 8.7] 6.2 [5.3, 8.3] 7.8 [6.3, 9.5] < 0.001 TG (mmol/l) 2.3 [1.5, 3.2] 2.1 [1.5, 2.5] 2.4 [1.7, 3.9] 0.06 Serum albumin (g/L) 25.5 [22.0, 29.5] 26.2 [23.8,29.6] 24.2 [19.1,28.6] 0.01 eGFR [ml/(min ∙1.73m 2 )] 116.3 [89.0, 138.1] 119.8 [101.6, 146.3] 106.2[78.7, 124.6] 0.01 UPCR (g/g.Cr) 2.8 [1.8, 4.3] 2.0 [1.3, 2.4] 4.4 [3.7, 6.0] < 0.001 Hb (g/l) 131.4 ± 19.5 130.6 ± 16.9 132.3 ± 22.3 0.64 Dysglycemia [n(%)] 35 (28.9%) 17 (25.8%) 18 (32.7%) 0.43 Hypertention [n(%)] 56 (46.3%) 27 (40.9%) 29 (52.7%) 0.21 IMN: idiopathic membranous nephropathy, TC:total cholesterol, TG: triglyceride, BMI: Body mass index, PCR: proteinuria to creatinine ratio, eGFR: estimated glomerular filtration rate, Hb:hemoglobin. 3.2. Outcomes of follow up During 6-month follow-up, the two groups comprised 66 low-risk and 55 intermediate-risk patients. The total remission (CR + PR) rate was 77.7% (94/121), with comparable rates between low-risk (80.3%, 53/66) and intermediate-risk groups (74.5%, 41/55) ( P = 0.51). However, CR rates differed significantly between groups, with the low-risk group achieving a higher rate (62.1%, 41/66) compared to the intermediate-risk group (41.8%, 23/55) ( P = 0.03). (Shown in Table 2) ‌Table 2. Remission rate at 6-month follow-up in 121 IMN patients Group All patients n = 121 Total Remission Complete Remission Yes (%) P -value Yes (%) P -value Low-risk group 66 53 (80.3%) 0.51 41(62.1%) 0.03 Intermediate-risk group 55 41 (74.5%) 23(41.8%) IMN: idiopathic membranous nephropathy. During 12-month follow-up, 15 (12.4%) patients lost follow-up. The final analyze at 12-mothe follow-up included 60 low-risk and 46 intermediate-risk patients. The total remission rate was 86.8% (92/106), with comparable total remission rates in the low-risk (83.3%, 50/60) and the intermediate-risk groups (91.3%, 42/46) ( χ² = 1.43, P = 0.36) (Table 3 ). The CR rate in 106 IMN patients was 70.8% (75/106), with no statistically significant difference observed between the low-risk (75.0%, 46/60) and intermediate-risk subgroups (65.2%, 30/46) ( χ² =1.20, P = 0.29) (Table 3 ). Table 3 Remission rate at 12-month follow-up in 106 IMN patients Group All patients n = 106 Total Remission Complete Remission Yes (%) P -value Yes (%) P -value Low-risk group 60 50 (83.3%) 0.36 45(75.0%) 0.29 Intermediate-risk group 46 42 (91.3%) 30(65.2%) IMN: idiopathic membranous nephropathy. 3.3. Factors associated with 6-month complete remission To identify factors associated with the 6-month CR rate, the binary logistic regression analyze was conducted. Initial univariate screening was followed by multivariate modeling incorporating the following covariates: low-risk group, serum albumin, total cholesterol, hemoglobin, dysglycemia, hypertension, age, and eGFR. The results showed that 6-month CR had a positive association with baseline serum albumin ( OR = 1.13, 95% CI : 1.03–1.24, P = 0.012), a negative association with dysglycemia ( OR = 0.38, 95% CI : 0.15–0.98, P = 0.045), intermediate-risk group ( OR = 0.41, 95% CI : 0.17–0.97, P = 0.042), while had no significant association with age, gender, triglyceride, and eGFR (all P > 0.05). (Shown in Table 4 ). Table 4 Related factors of 6-month complete remission in 121 IMN patients Variable B Wald χ² P OR 95% CI Intermediate-risk group (yes v.s no) -0.91 4.16 0.042 0.40 0.17–0.97 Serum albumin (g/L) 0.12 6.34 0.012 1.13 1.03–1.24 Triglyceride (mmol/L) -0.04 0.72 0.395 0.96 0.87–1.06 Gender 0.42 0.87 0.352 1.52 0.63–3.64 Dysglycemia (yes v.s no) -0.97 4.01 0.045 0.38 0.15–0.98 Age(year) -0.01 0.65 0.419 0.99 0.95–1.02 eGFR(ml/min/1.73m 2 ) -0.01 0.97 0.32 0.99 0.98–1.01 IMN: idiopathic membranous nephropathy, OR: odds ratio, CI: confidence interval, eGFR: estimated glomerular filtration rate 3.4. Comparison of infection events and infection-related mortality In the 121 IMN patients, infectious events were documented in 9 (7.4%) cases, comprising 1 herpes zoster, 1 urinary tract infection, 3 bacterial pneumonia, and 4 Pneumocystis jirovecii pneumonia (PCP). The infection distribution showed 6 cases in the low-risk group (1 herpes zoster, 2 bacterial pneumonia, 3 PCP) and 3 cases in the intermediate-risk group (1 urinary tract infection, 1 bacterial pneumonia, 1 PCP), with no significant difference ( P > 0.05) (Shown in Table 5 ). Importantly, no infection-related mortality occurred during follow-up. Table 5 Comparison of infection events and infection-related mortality during follow-up Group Infections [n(%)] χ 2 P Infection-related mortality [n(%)] Low-risk group (n = 66) 6 (9.1%) 0.17 0.68 0 (0%) Intermediate-risk group (n = 55) 3 (5.5%) 0 (0%) 4. Discussion Idiopathic Membranous nephropathy represents a common form of chronic kidney disease, with proteinuria serving as an independent prognostic risk factor in IMN[ 16 ]. The 2021 KDIGO guidelines[ 8 ] suggest that approximately one-third of IMN patients may achieve spontaneous remission, supporting wait and see for low to intermediate risk cases, immunosuppressive therapy should be offered to patients with a medium or high risk of renal progression[ 17 ]. But, the early identification of such medium- or high-risk patients remains elusive[ 18 ]. However, clinical evidence confirms that early proteinuria remission reduce the decline in eGFR[ 19 ]. Early reduction in proteinuria is strongly associated with improved outcomes[ 20 ]. Achieving early remission predicts better long-term renal survival[ 21 ], early complete remission (urinary protein < 0.3g/day) reduces the 10-year risk of end-stage renal disease by 72%[ 22 ]. These findings emphasized the critical importance of timely remission for effective disease management. We retrospectively analyzed 121 patients with biopsy-confirmed IMN, all of whom strongly requested to undergo immunotherapy. The patients were stratified into two groups based on urinary PCR levels for efficacy evaluation of immunosuppressive therapy. The intermediate-risk group had higher urinary PCR and lower serum albumin, those two were negatively correlated, and that was aligned with Cattran DC[ 23 ] and Polanco’s finding[ 5 ]. The low-risk group demonstrated superior clinical outcomes with an 80.3% total remission rate at 6 months, significantly surpassing the 14% remission rate reported by B M[ 24 ] and the 22% remission rate reported by Shimizu Sv[ 25 ], and meanwhile no significant increase in adverse infection events. At 12 months, the low-risk group achieved an 83.3% total remission rate, markedly higher than the rates of 30%[ 20 ], and 28%[ 5 ] reported in previous studies. While both groups achieved similar renal remission rates (83.3% v.s 91.3%) and CR rates (75.0% v.s 65.2%) at 12 months, these findings contrast with Alsharhan's[ 26 ] report of lower remission in high-proteinuria patients (45% v.s 68%), potentially reflecting our study's retrospective design, selection bias, and our active treatment toward adherent patients. Whether 6 months or 12 months, the low-risk group remission rate is higher than the approximately one-third of spontaneous remission rate[ 8 ]. The study by Ji-Young Choi et al. revealed the following findings in a propensity score-matched cohort[ 27 ]: Although baseline characteristics of patients achieving remission showed no significant differences between the immunosuppressant group and the conservative treatment group, the 12-month cumulative remission rate was significantly higher in the immunosuppressant group within the overall population. Concurrently, renal survival rates were comparable between the two groups in the overall population. At the 6-month follow-up, the low-risk cohort demonstrated a significantly higher complete remission (CR) rate. Multivariate analysis revealed that baseline serum albumin levels, presence of dysglycemia at baseline, and urinary protein-to-creatinine ratio (uPCR) levels were independent predictors of proteinuria remission. This observation corroborates Beck's[ 28 ] finding that patients with lower baseline proteinuria levels are more likely to achieve remission. This finding is consistent with Cattran's[ 29 ] study, which demonstrated that in immunosuppression-treated IMN patients, baseline serum albumin levels < 3.0 g/dL were independently associated with significantly reduced 6-month remission rates. Dysglycemia is known as an independent risk factor for chronic kidney disease (CKD)[ 30 – 32 ], which is consistent with our findings regarding dysglycemia's impact on proteinuria remission. The study failed to demonstrate any statistically significant association with age, that were consistented with despite worse renal function at baseline, remission rates between older and younger patients appear comparable[ 33 , 34 ]. This result perhapers related to the well-balanced demographic characteristics between the comparative cohorts. In our study, gender (male/female) was not an independent predictor of proteinuria relief within 6 months. This finding contrasts with previous studies suggesting that male gender is associated with a lower likelihood of spontaneous remission[ 35 ]. Additionally, male patients had higher baseline proteinuria levels, which may influence long-term prognosis[ 36 ]. Hyperlipidemia intervention increased cardiovascular risk, and the use of statins can effectively reduce the occurrence of venous thromboembolic events[ 37 ], while it does not directly affect immunotherapy efficacy, this aligns with that hyperlipidemia exerted no impact on proteinuria remission[ 38 ]. The most common complication associated with immunosuppressive therapy is infection, common sites of infection include respiratory tract, urinary tract, digestive tract and skin[ 10 ]. Patients receiving immunosuppressive therapy may experience severe infections, and infection is a significant safety concern that must be addressed when considering immunosuppressive treatment for patients with IMN. In the study, we observed overall infection rate was markedly reduced at 7.3% - significantly lower than the 42.1% rate reported by Eren Sadioglu R[ 39 ]. Notably, severe infections in our study were pneumocystispneumonia, we identified four cases of confirmed pneumocystispneumonia, constituting a 3.3% severe infection rate (4/121). The low-risk group demonstrated a 9.1% infection rate (6/66), while the intermediate-risk group showed a 5.5% rate (3/55), both rates were lower than the 27.6% infection rate reported by Yan P[ 40 ], the 21.8% infection rate reported by Choi JY[ 27 ]. This discrepancy may reflect our institution's rigorous prophylactic protocol, including systematic pneumocystis pneumonia prophylaxis for all patients receiving high-dose immunosuppression. Current evidence on the efficacy of immunosuppressive therapy in low-risk IMN is limited. This study firstly addressed this knowledge gap and initially demonstrated the effecy and safety of immunosuppressive treatment for low-risk IMN patients. However, this study presents several limitations, including single-center study, limited sample size, and short follow-up duration. These limitations highlight the necessary for future prospective multicenter studies incorporating comprehensive clinical parameters and extended observation periods to corroborate these preliminary observations. 5. Conclusion Regardless of whether the treatment duration was 6 months or 12 months, immunosuppressive therapy increased the total and complete proteinuria remission rates of patients in low-risk group without increasing the risk of infection and mortality. Moreover, the complete remission at 6-month follow-up in low-risk group demonstrated significantly superior outcomes with the intermediate-risk group. Declarations Clinical trial number: not applicable. Acknowledgements We thank all the participants and their family members and all study person nel for their great contributions throughout the study. Author contributions Yan Jin enrolled the patients in the study, collected the data, and prepared the manuscript. Yan Zhang, Lei Lan and Wei Chen contributed to the concept and design. Chaoyi Chen collected the data. Jielong Jiang and Jun Jiang supervised the study. All authors have read and approved the final manuscript. Ethics approval and consent to participate All participants signed informed consent and agreed to clinical data for clinical analysis at the time of admission. This study was conducted in accordance with theprinciples of the Declaration of Helsinki. The research ethics committee of AnhuiProvincial Hospital approved the study protocol (Approval No.: 2025KY404). Disclosure statement On behalf of all authors, the corresponding author states that there is no conflict of interest to disclose. Funding This work was not supported by any grant. Data availability statement Readers can access the data underlying the study’s findings by contacting the corresponding author. References McGrogan A, Franssen CF, de Vries CS. 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Dysglycemia predicts cardiovascular and kidney disease in the Kidney Early Evaluation Program. J Clin Hypertens (Greenwich). 2010;12(1):51–8. http://doi.org/10.1111/j.1751-7176.2009.00190.x . Barbour SJ, Fervenza FC, Induruwage D, et al. Anti-PLA2R Antibody Levels and Clinical Risk Factors for Treatment Nonresponse in Membranous Nephropathy. Clin J Am Soc Nephrol. 2023;18(10):1283–93. http://doi.org/10.2215/cjn.0000000000000237 . Paulo R, Jorge LB, Yu L, et al. Diagnosis and Course of Membranous Nephropathy in Adults: Comparison by Age Group. Kidney Blood Press Res. 2022;47(12):693–701. http://doi.org/10.1159/000527368 . Cattran DC, Pei Y, Greenwood CM, et al. Validation of a predictive model of idiopathic membranous nephropathy: its clinical and research implications. Kidney Int. 1997;51(3):901–7. .http://doi.org/10.1038/ki.1997.127 . Bobart SA, Portalatin G, Sawaf H et al. The Cleveland Clinic Kidney Biopsy Epidemiological Project, Kidney360 3(12) (2022) 2077–85 http://doi.org/10.34067/kid.0005882022 Zou P, Li H, Cai J, et al. Statins can benefit patients with primary membranous nephropathy on venous thromboembolism. Ren Fail. 2021;43(1):302–6. http://doi.org/10.1080/0886022x.2021.1879853 . Shi GQ, Yu R, Wu Y, et al. Obinutuzumab for PLA2R-associated membranous nephropathy. Nephrol Dial Transpl. 2025. http://doi.org/10.1093/ndt/gfaf165 . Eren Sadioglu R, Eyupoglu S, Erdogmus S, et al. Infectious Complications in Patients with Primary Glomerulonephritis over 10 Years: A Single-Center Experience in Turkey. Kidney Dis (Basel). 2021;7(1):57–66. http://doi.org/10.1159/000510153 . Yan P, Fang X, Ke B. Optimized rituximab regimen versus recommended regimen for idiopathic membranous nephropathy: A single-center retrospective cohort study. Int Immunopharmacol. 2024;130:111718. http://doi.org/10.1016/j.intimp.2024.111718 . 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University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Zhang","suffix":""},{"id":538926042,"identity":"2e4a2433-562f-4f0f-90ab-ec6c5ddc46d5","order_by":2,"name":"Lei Lan","email":"","orcid":"","institution":"Anhui Provincial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Lan","suffix":""},{"id":538926043,"identity":"42283d1a-79bf-44b2-b924-24f439960abc","order_by":3,"name":"Wei Chen","email":"","orcid":"","institution":"Anhui Provincial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Chen","suffix":""},{"id":538926044,"identity":"13a72940-1fd5-4891-bb93-24a34e1a0e49","order_by":4,"name":"ChaoYi Chen","email":"","orcid":"","institution":"Anhui Provincial 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Jiang","email":"","orcid":"","institution":"Anhui Provincial Hospital","correspondingAuthor":false,"prefix":"","firstName":"JieLong","middleName":"","lastName":"Jiang","suffix":""}],"badges":[],"createdAt":"2025-09-23 15:38:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7696079/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7696079/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95502027,"identity":"258b58b4-a35b-467a-99c7-98868ca290b6","added_by":"auto","created_at":"2025-11-10 05:34:56","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2354962,"visible":true,"origin":"","legend":"","description":"","filename":"RevisedManuscript.doc","url":"https://assets-eu.researchsquare.com/files/rs-7696079/v1/8f1aced523de4884eda88dee.doc"},{"id":95528022,"identity":"29ab3fa9-df6e-4e9e-a07f-84cc52cc05a6","added_by":"auto","created_at":"2025-11-10 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05:34:56","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":127520,"visible":true,"origin":"","legend":"","description":"","filename":"86d8e658b8f74020b9b08211a36bd7971enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7696079/v1/dfd9cd8e36ee59e9291de3dc.xml"},{"id":95502026,"identity":"bc26be41-4493-4408-bfdc-10a764211c80","added_by":"auto","created_at":"2025-11-10 05:34:56","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":125392,"visible":true,"origin":"","legend":"","description":"","filename":"86d8e658b8f74020b9b08211a36bd7971structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7696079/v1/e4dda49ab4b43964c38990be.xml"},{"id":95529051,"identity":"a7adc1cc-fadf-40ca-88a5-720ebea10998","added_by":"auto","created_at":"2025-11-10 10:16:44","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":135973,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7696079/v1/9a8e137ff9f1c2122e8ceae6.html"},{"id":95502022,"identity":"0186a850-c150-41a3-b475-99c9891f6e53","added_by":"auto","created_at":"2025-11-10 05:34:56","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":911612,"visible":true,"origin":"","legend":"\u003cp\u003eElectron microscopy shows the deposition of immune complexes beneath the glomerular basement membrane.(1A) Immunofluorescence shows PLA2R deposits along the glomerular capillary walls.(1B)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7696079/v1/cc950863e8e7a4535cd9270c.png"},{"id":97893562,"identity":"217ee7ba-84e6-4700-92b9-41d1bb0d7440","added_by":"auto","created_at":"2025-12-10 15:30:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1758068,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7696079/v1/09d148f6-1f29-4c2c-84cc-eb55d7aca8ac.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of immunosuppressive therapy in low-risk and intermediate- risk idiopathic membranous nephropathy patients","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eIdiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults and a significant contributor to end-stage renal disease (ESRD)[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Its pathogenesis is primarily associated with the deposition of immune complexes beneath the glomerular basement membrane podocytes, with anti-phospholipase A2 receptor (PLA2R) antibodies playing a key role in disease development[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].(Image 1) In terms of natural history, approximately 30% of IMN patients may progress to ESRD within 10\u0026ndash;15 years, while about 30% achieve spontaneous remission. The remaining patients exhibit persistent proteinuria with relatively stable renal function[\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Given the significant heterogeneity in clinical manifestations of IMN and the risks associated with immunosuppressive therapy\u0026mdash;such as infections, metabolic disorders, and bone marrow suppression\u0026mdash;both domestic and international guidelines emphasize the importance of risk-stratified treatment strategies. 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend supportive care and close monitoring for 6\u0026ndash;12 months for low- and intermediate-risk patients, whereas high-risk patients with persistent nephrotic-range proteinuria (\u0026gt;\u0026thinsp;3.5 g/24 h) or ongoing renal function deterioration should initiate immunosuppressive therapy as early as possible[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe treatment goals for IMN include not only inducing proteinuria remission and delaying renal function progression but also improving patients' quality of life and minimizing treatment-related adverse events, such as infections, thromboembolic events, and cardiovascular complications[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Current clinical treatment options are diverse, including corticosteroids combined with alkylating agents, calcineurin inhibitors (such as tacrolimus and cyclosporine), biologics like rituximab, and novel targeted agents[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Among these regimens, immunosuppressive therapy is strongly recommended for patients with persistent severe proteinuria, as it may reduce the risk of disease relapse and help delay the progression to ESRD[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. More than 30 years have passed since immunosuppressants were first used in the treatment of IMN[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], during which various immunosuppressive regimens have been proposed. Numerous studies have shown that, compared with supportive care alone, immunosuppressive therapy significantly improves proteinuria remission rates and slows the progression to ESRD[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, the efficacy and safety of different treatment regimens require further investigation[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The use of immunosuppressants is a critical factor influencing clinical outcomes, yet comparative studies on the long-term efficacy of these drugs in large IMN patient cohorts are still limited. Therefore, this study aims to evaluate the impact of immunosuppressive agents on clinical outcomes in a cohort of IMN patients.\u003c/p\u003e\u003cp\u003eThis retrospective analysis included 121 IMN patients who received immunosuppressants as initial treatment. Based on baseline urine protein-to-creatinine ratio (PCR), patients were stratified into a low-risk group (PCR\u0026thinsp;\u0026le;\u0026thinsp;3.0 g/g) and an intermediate-risk group (PCR\u0026thinsp;\u0026gt;\u0026thinsp;3.0 g/g). Treatment efficacy and infection risk were assessed by comparing proteinuria remission rates and the incidence of infectious events between the two groups.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Data collection\u003c/h2\u003e\u003cp\u003eWe retrospectively enrolled 121 patients with biopsy-confirmed IMN from the Nephrology Department of the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) between 2021 and 2023. The inclusion criteria comprised: (1) renal biopsy-confirmed IMN; (2) adult patients (aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years); (3) no prior immunosuppressive therapy; (4) signed informed consent. Exclusion criteria included: (1) secondary MN (including but not limited to lupus-associated, hepatitis-related, drug/toxin-induced, or malignancy-associated forms); (2) any history of immunosuppressive therapy; (3) inadequate follow-up duration (\u0026lt;6 month); (4) estimated glomerular filtration rate (eGFR)\u0026thinsp;\u0026lt;\u0026thinsp;30ml/min /1.73 m\u003csup\u003e2\u003c/sup\u003e. This study protocol adheres to the principles of the Declaration of Helsinki and complies with relevant Chinese clinical trial regulations and laws. It has been approved by the Medical Ethics Committee of the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) (Approval No.: 2025KY404). Written informed consent was obtained from all participants' guardians in accordance with the guiding principles of the Declaration of Helsinki.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Methods\u003c/h2\u003e\u003cp\u003eUsing the hospital's database, we retrospectively collected the demographic information and clinical data, including: (1) Demographic characteristics: age, gender, and body mass index (BMI); (2) Laboratory parameters: urinary PCR, serum creatinine, eGFR, serum albumin (ALB), total cholesterol (TC), triglycerides (TG), hemoglobin, as well as binary variables indicating the presence or absence of dysglycemia and hypertension. Clinical outcomes and infection events were systematically documented.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Definitions\u003c/h2\u003e\u003cp\u003eeGFR was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Therapeutic responses were classified into three categories: (1) Partial remission (PR): \u0026ge;50% reduction in urinary PCR from baseline values; (2) Complete remission (CR): urinary PCR\u0026thinsp;\u0026lt;\u0026thinsp;0.5 g/g Cr concurrent with serum albumin normalization (\u0026gt;\u0026thinsp;35 g/l); (3) Treatment failure: inability to achieve either PR or CR criteria[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Total remission included partial remission and complete remission.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Statistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analyses were conducted by IBM SPSS Statistics (Version 26.0; IBM Corp., Armonk, NY, USA). Normally distributed continuous variables were described as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and compared by independent samples \u003cem\u003et\u003c/em\u003e-test. Non-normally distributed continuous variables were described as median (interquartile range, IQR) and compared by \u003cem\u003eMann-Whitney U\u003c/em\u003e test. Categorical variables were described as frequencies (percentages), between-group differences compared by \u003cem\u003ePearson's χ\u0026sup2;\u003c/em\u003e or \u003cem\u003eFisher's exact\u003c/em\u003e test depending on expected counts. The primary efficacy endpoints included CR and total remission (CR\u0026thinsp;+\u0026thinsp;PR) rate. To identify independent predictors of proteinuria remission, Binary logistic regression analyses were performed adjusting for relevant covariates, with results reported as odds ratio (\u003cem\u003eOR\u003c/em\u003e) and 95% confidence interval (\u003cem\u003eCI\u003c/em\u003e). All statistical tests were two-tailed, with statistical significance defined as \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Baseline characteristics of the 121 IMN patients\u003c/h2\u003e\u003cp\u003eThe study comprised 121 biopsy-confirmed IMN patients, including 71 males (58.7%) and 50 females (41.3%). Baseline characteristics were as follows: age 52.0 [41.0\u0026ndash;58.0] years, urinary PCR 2.8 [1.8, 4.3] g/g Cr, eGFR 116.3 [89.0, 138.1] ml/min/1.73m\u0026sup2;, and serum albumin 25.5 [22.0, 29.5] g/L. Based on baseline urinary PCR levels, risk stratification classified 66 patients (54.5%) as low-risk group and 55 patients (45.5%) as intermediate-risk group. Comparative analysis demonstrated statistically significant intergroup differences in TC, TG, eGFR, urinary PCR, and serum albumin levels (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). No significant differences were observed in age, sex, BMI, TG, hemoglobin, dysglycemia, and hypertension between the groups (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). (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 121 IMN patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAll patients\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLow-risk group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIntermediate-risk group (n\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e52.0 [41.0, 58.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e51.5[39.0, 57.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e52.0 [41.0, 60.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex [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\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e71.0 [58.7%]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e37.0 [56.1%]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e34.0 [61.8%]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.58\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e50.0 [41.3%]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29.0 [42.9%]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e21.0 [38.2%]\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=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24.5 [22.7, 27.1]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24.6 [22.6, 26.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e24.2 [22.8, 27.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.48\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTC (mmol/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7.2 [5.8, 8.7]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6.2 [5.3, 8.3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.8 [6.3, 9.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTG (mmol/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.3 [1.5, 3.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.1 [1.5, 2.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.4 [1.7, 3.9]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum albumin (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25.5 [22.0, 29.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e26.2 [23.8,29.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e24.2 [19.1,28.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.01\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=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e116.3 [89.0, 138.1]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e119.8 [101.6, 146.3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e106.2[78.7, 124.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUPCR (g/g.Cr)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.8 [1.8, 4.3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.0 [1.3, 2.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.4 [3.7, 6.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb (g/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e131.4\u0026thinsp;\u0026plusmn;\u0026thinsp;19.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e130.6\u0026thinsp;\u0026plusmn;\u0026thinsp;16.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e132.3\u0026thinsp;\u0026plusmn;\u0026thinsp;22.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDysglycemia [n(%)]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e35 (28.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e17 (25.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e18 (32.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.43\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertention [n(%)]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e56 (46.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27 (40.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e29 (52.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.21\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\u003eIMN: idiopathic membranous nephropathy, TC:total cholesterol, TG: triglyceride, BMI: Body mass index, PCR: proteinuria to creatinine ratio, eGFR: estimated glomerular filtration rate, Hb:hemoglobin.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.2. Outcomes of follow up\u003c/h2\u003e\u003cp\u003eDuring 6-month follow-up, the two groups comprised 66 low-risk and 55 intermediate-risk patients. The total remission (CR\u0026thinsp;+\u0026thinsp;PR) rate was 77.7% (94/121), with comparable rates between low-risk (80.3%, 53/66) and intermediate-risk groups (74.5%, 41/55) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.51). However, CR rates differed significantly between groups, with the low-risk group achieving a higher rate (62.1%, 41/66) compared to the intermediate-risk group (41.8%, 23/55) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03). (Shown in Table\u0026nbsp;2)\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026zwnj;Table 2. Remission rate at 6-month follow-up in 121 IMN patients\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"6\"\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\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAll patients\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;121\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eTotal Remission\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eComplete Remission\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eYes (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow-risk group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53 (80.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e41(62.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntermediate-risk group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41 (74.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23(41.8%)\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\u003eIMN: idiopathic membranous nephropathy.\u003c/p\u003e\u003cp\u003eDuring 12-month follow-up, 15 (12.4%) patients lost follow-up. The final analyze at 12-mothe follow-up included 60 low-risk and 46 intermediate-risk patients. The total remission rate was 86.8% (92/106), with comparable total remission rates in the low-risk (83.3%, 50/60) and the intermediate-risk groups (91.3%, 42/46) (\u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 1.43, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.36) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The CR rate in 106 IMN patients was 70.8% (75/106), with no statistically significant difference observed between the low-risk (75.0%, 46/60) and intermediate-risk subgroups (65.2%, 30/46) (\u003cem\u003eχ\u0026sup2;\u003c/em\u003e=1.20, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.29) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\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 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRemission rate at 12-month follow-up in 106 IMN patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\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\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAll patients\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;106\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eTotal Remission\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eComplete Remission\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eYes (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow-risk group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50 (83.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e45(75.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntermediate-risk group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42 (91.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e30(65.2%)\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\u003eIMN: idiopathic membranous nephropathy.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.3. Factors associated with 6-month complete remission\u003c/h2\u003e\u003cp\u003eTo identify factors associated with the 6-month CR rate, the binary logistic regression analyze was conducted. Initial univariate screening was followed by multivariate modeling incorporating the following covariates: low-risk group, serum albumin, total cholesterol, hemoglobin, dysglycemia, hypertension, age, and eGFR. The results showed that 6-month CR had a positive association with baseline serum albumin (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.13, 95% \u003cem\u003eCI\u003c/em\u003e: 1.03\u0026ndash;1.24, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012), a negative association with dysglycemia (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.38, 95% \u003cem\u003eCI\u003c/em\u003e: 0.15\u0026ndash;0.98, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045), intermediate-risk group (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.41, 95% \u003cem\u003eCI\u003c/em\u003e: 0.17\u0026ndash;0.97, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.042), while had no significant association with age, gender, triglyceride, and eGFR (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). (Shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\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 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRelated factors of 6-month complete remission in 121 IMN patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eWald χ\u0026sup2;\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003e95% CI\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntermediate-risk group (yes \u003cem\u003ev.s\u003c/em\u003e no)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.042\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.17\u0026ndash;0.97\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum albumin (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.03\u0026ndash;1.24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTriglyceride (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.395\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.87\u0026ndash;1.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.352\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.63\u0026ndash;3.64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDysglycemia (yes \u003cem\u003ev.s\u003c/em\u003e no)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.045\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.15\u0026ndash;0.98\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge(year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.419\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.95\u0026ndash;1.02\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=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.98\u0026ndash;1.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eIMN: idiopathic membranous nephropathy, OR: odds ratio, CI: confidence interval, eGFR: estimated glomerular filtration rate\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.4. Comparison of infection events and infection-related mortality\u003c/h2\u003e\u003cp\u003eIn the 121 IMN patients, infectious events were documented in 9 (7.4%) cases, comprising 1 herpes zoster, 1 urinary tract infection, 3 bacterial pneumonia, and 4 Pneumocystis jirovecii pneumonia (PCP). The infection distribution showed 6 cases in the low-risk group (1 herpes zoster, 2 bacterial pneumonia, 3 PCP) and 3 cases in the intermediate-risk group (1 urinary tract infection, 1 bacterial pneumonia, 1 PCP), with no significant difference (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Importantly, no infection-related mortality occurred during follow-up.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of infection events and infection-related mortality during follow-up\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" 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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInfections [n(%)]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eInfection-related mortality [n(%)]\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow-risk group (n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntermediate-risk group (n\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (5.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIdiopathic Membranous nephropathy represents a common form of chronic kidney disease, with proteinuria serving as an independent prognostic risk factor in IMN[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The 2021 KDIGO guidelines[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] suggest that approximately one-third of IMN patients may achieve spontaneous remission, supporting wait and see for low to intermediate risk cases, immunosuppressive therapy should be offered to patients with a medium or high risk of renal progression[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. But, the early identification of such medium- or high-risk patients remains elusive[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, clinical evidence confirms that early proteinuria remission reduce the decline in eGFR[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Early reduction in proteinuria is strongly associated with improved outcomes[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Achieving early remission predicts better long-term renal survival[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], early complete remission (urinary protein\u0026thinsp;\u0026lt;\u0026thinsp;0.3g/day) reduces the 10-year risk of end-stage renal disease by 72%[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. These findings emphasized the critical importance of timely remission for effective disease management.\u003c/p\u003e\u003cp\u003eWe retrospectively analyzed 121 patients with biopsy-confirmed IMN, all of whom strongly requested to undergo immunotherapy. The patients were stratified into two groups based on urinary PCR levels for efficacy evaluation of immunosuppressive therapy. The intermediate-risk group had higher urinary PCR and lower serum albumin, those two were negatively correlated, and that was aligned with Cattran DC[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and Polanco\u0026rsquo;s finding[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The low-risk group demonstrated superior clinical outcomes with an 80.3% total remission rate at 6 months, significantly surpassing the 14% remission rate reported by B M[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and the 22% remission rate reported by Shimizu Sv[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and meanwhile no significant increase in adverse infection events. At 12 months, the low-risk group achieved an 83.3% total remission rate, markedly higher than the rates of 30%[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], and 28%[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] reported in previous studies. While both groups achieved similar renal remission rates (83.3% \u003cem\u003ev.s\u003c/em\u003e 91.3%) and CR rates (75.0% \u003cem\u003ev.s\u003c/em\u003e 65.2%) at 12 months, these findings contrast with Alsharhan's[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] report of lower remission in high-proteinuria patients (45% \u003cem\u003ev.s\u003c/em\u003e 68%), potentially reflecting our study's retrospective design, selection bias, and our active treatment toward adherent patients. Whether 6 months or 12 months, the low-risk group remission rate is higher than the approximately one-third of spontaneous remission rate[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The study by Ji-Young Choi et al. revealed the following findings in a propensity score-matched cohort[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]: Although baseline characteristics of patients achieving remission showed no significant differences between the immunosuppressant group and the conservative treatment group, the 12-month cumulative remission rate was significantly higher in the immunosuppressant group within the overall population. Concurrently, renal survival rates were comparable between the two groups in the overall population.\u003c/p\u003e\u003cp\u003eAt the 6-month follow-up, the low-risk cohort demonstrated a significantly higher complete remission (CR) rate. Multivariate analysis revealed that baseline serum albumin levels, presence of dysglycemia at baseline, and urinary protein-to-creatinine ratio (uPCR) levels were independent predictors of proteinuria remission. This observation corroborates Beck's[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] finding that patients with lower baseline proteinuria levels are more likely to achieve remission. This finding is consistent with Cattran's[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] study, which demonstrated that in immunosuppression-treated IMN patients, baseline serum albumin levels\u0026thinsp;\u0026lt;\u0026thinsp;3.0 g/dL were independently associated with significantly reduced 6-month remission rates. Dysglycemia is known as an independent risk factor for chronic kidney disease (CKD)[\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], which is consistent with our findings regarding dysglycemia's impact on proteinuria remission. The study failed to demonstrate any statistically significant association with age, that were consistented with despite worse renal function at baseline, remission rates between older and younger patients appear comparable[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. This result perhapers related to the well-balanced demographic characteristics between the comparative cohorts. In our study, gender (male/female) was not an independent predictor of proteinuria relief within 6 months. This finding contrasts with previous studies suggesting that male gender is associated with a lower likelihood of spontaneous remission[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Additionally, male patients had higher baseline proteinuria levels, which may influence long-term prognosis[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Hyperlipidemia intervention increased cardiovascular risk, and the use of statins can effectively reduce the occurrence of venous thromboembolic events[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], while it does not directly affect immunotherapy efficacy, this aligns with that hyperlipidemia exerted no impact on proteinuria remission[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe most common complication associated with immunosuppressive therapy is infection, common sites of infection include respiratory tract, urinary tract, digestive tract and skin[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Patients receiving immunosuppressive therapy may experience severe infections, and infection is a significant safety concern that must be addressed when considering immunosuppressive treatment for patients with IMN. In the study, we observed overall infection rate was markedly reduced at 7.3% - significantly lower than the 42.1% rate reported by Eren Sadioglu R[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Notably, severe infections in our study were pneumocystispneumonia, we identified four cases of confirmed pneumocystispneumonia, constituting a 3.3% severe infection rate (4/121). The low-risk group demonstrated a 9.1% infection rate (6/66), while the intermediate-risk group showed a 5.5% rate (3/55), both rates were lower than the 27.6% infection rate reported by Yan P[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e], the 21.8% infection rate reported by Choi JY[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. This discrepancy may reflect our institution's rigorous prophylactic protocol, including systematic pneumocystis pneumonia prophylaxis for all patients receiving high-dose immunosuppression.\u003c/p\u003e\u003cp\u003eCurrent evidence on the efficacy of immunosuppressive therapy in low-risk IMN is limited. This study firstly addressed this knowledge gap and initially demonstrated the effecy and safety of immunosuppressive treatment for low-risk IMN patients. However, this study presents several limitations, including single-center study, limited sample size, and short follow-up duration. These limitations highlight the necessary for future prospective multicenter studies incorporating comprehensive clinical parameters and extended observation periods to corroborate these preliminary observations.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eRegardless of whether the treatment duration was 6 months or 12 months, immunosuppressive therapy increased the total and complete proteinuria remission rates of patients in low-risk group without increasing the risk of infection and mortality. Moreover, the complete remission at 6-month follow-up in low-risk group demonstrated significantly superior outcomes with the intermediate-risk group.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the participants and their family members and all study person nel for their great contributions throughout the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYan Jin enrolled the patients in the study, collected the data, and prepared the manuscript. Yan Zhang, Lei Lan and Wei Chen contributed to the concept and design. Chaoyi Chen collected the data. Jielong Jiang and Jun Jiang supervised the study. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants signed informed consent and agreed to clinical data for clinical analysis at the time of admission. This study was conducted in accordance with theprinciples of the Declaration of Helsinki. The research ethics committee of AnhuiProvincial Hospital approved the study protocol (Approval No.: 2025KY404).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn behalf of all authors, the corresponding author states that there is no conflict of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was not supported by any grant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eReaders can access the data underlying the study’s findings by contacting the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMcGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. 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Optimized rituximab regimen versus recommended regimen for idiopathic membranous nephropathy: A single-center retrospective cohort study. Int Immunopharmacol. 2024;130:111718. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1016/j.intimp.2024.111718\u003c/span\u003e\u003cspan address=\"10.1016/j.intimp.2024.111718\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Idiopathic membranous nephropathy, Immunosuppressive Therapy, Efficacy, Infection","lastPublishedDoi":"10.21203/rs.3.rs-7696079/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7696079/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe efficacy and safety of immunosuppressive therapy for low- and intermediate-risk idiopathic membranous nephropathy remains unclear.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethod\u003c/b\u003e\u003c/p\u003e\u003cp\u003e121 renal biopsy-confirmed idiopathic membranous nephropathy (IMN) patients were retrospectively included from the Department of Nephrology in the First Affiliated Hospital of USTC from 2021 to 2023. Participants were stratified by baseline urinary protein-to-creatinine ratio (PCR) (low-risk group\u0026thinsp;\u0026le;\u0026thinsp;3.0g/gCr \u003cem\u003ev.s\u003c/em\u003e intermediate-risk group\u0026thinsp;\u0026gt;\u0026thinsp;3.0g/gCr) and received immunosuppressive therapy at initial treatment. During a 12-month follow-up, proteinuria remission rates at 6 month and 12 month were compared between the two groups, and concurrently documented infectious events. Binary logistic regression analyze was conducted to identify the risk factors for proteinuria remission.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDuring a 6-month follow-up, complete proteinuria remission rates in low-risk group was significantly higher than intermediate-risk group (62.1% \u003cem\u003ev.s\u003c/em\u003e 41.8%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03), but there were no significant difference on total proteinuria remission rates between low-risk group and intermediate-risk group (80.3% \u003cem\u003ev.s\u003c/em\u003e 74.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.51). Binary logistic regression analyze showed that baseline serum albumin (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.17, 95%\u003cem\u003eCI\u003c/em\u003e:1.06\u0026ndash;1.29, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01), glycemic abnormality (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.32, 95% \u003cem\u003eCI\u003c/em\u003e:0.12\u0026ndash;0.86, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02), intermediate-risk group (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.41, 95% \u003cem\u003eCI\u003c/em\u003e: 0.19\u0026ndash;0.99, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04), and hemoglobin as independent predictors for complete proteinuria remission at 6 month. During 12 months, total proteinuria remission rate (83.3% \u003cem\u003ev.s\u003c/em\u003e 91.3%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.36) and complete proteinuria remission rate (75.0% \u003cem\u003ev.s\u003c/em\u003e 65.2%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.29) had no significant difference between the two groups. Overall infection incidence was 7.4% (9/121), with no difference between the two groups, and no mortality events observed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e\u003cp\u003eImmunosuppressive therapy increased the total and complete proteinuria remission rates of patients in low-risk group without increasing the risk of infection.\u003c/p\u003e","manuscriptTitle":"Efficacy of immunosuppressive therapy in low-risk and intermediate- risk idiopathic membranous nephropathy patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-10 05:34:51","doi":"10.21203/rs.3.rs-7696079/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"52fdcfdb-a3c0-4eef-b9d0-23deacb4bd46","owner":[],"postedDate":"November 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-08T14:23:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-10 05:34:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7696079","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7696079","identity":"rs-7696079","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}