Could the total renal chronicity score at renal biopsy and baseline creatinine be predictive of long-term renal survival in primary membranous nephropathy patients?

Could the total renal chronicity score at renal biopsy and baseline creatinine be predictive of long-term renal survival in primary 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 Could the total renal chronicity score at renal biopsy and baseline creatinine be predictive of long-term renal survival in primary membranous nephropathy patients? Hasan Kocaayan, Yusuf Uzum, Ibrahim Ertekin, Fulya Cakalagaoglu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5968053/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 Objective: Renal survival is important in patients with idiopathic membranous nephropathy (IMN). In this study we investigated the factors affecting renal survival in IMN patients Methods: This retrospective single center cohort study included patients who were diagnosed with IMN by renal biopsy between January 2009 and February 2019 and had a 5-year follow-up. Age, gender, serum creatinine, serum albumin, 24-hour proteinuria of the patients at the time of renal biopsy were recorded. The total renal chronicity score was calculated from the results of renal biopsy and patients were divided into minimal and non-minimal (including mild, moderate and severe) according to the total chronicity score. Renal survival was defined as at least a two-fold increase in serum creatinine from baseline and the need for renal replacement treatment (RRT). Results: Twenty patients (40%) had doubled serum creatinine levels or needed RRT. In univariate analysis, age, serum creatinine, serum albumin, serum albumin grade (<3g/dl) and total renal chronicity grade were found to be risk factors for renal survival. Multivariate Cox regression analysis revealed that the serum creatinine level [hazard ratio (HR) 2.38, confidence interval (CI) 1.37-4.11, p=0.02], serum albumin level (HR 0.43, CI 0.23-0.8, p=0.008) and total renal chronicity score grade (HR 14.4, CI 3.2-64.6, p:<0.001) were independent risk factors for renal survival. Conclusions: Low albumin levels (especially <3g/dl), high serum creatinine levels and high total renal chronicity scores (the presence of non-minimal degree of chronic change) on renal biopsy at the time of diagnosis are predictive of poor renal survival. idiopathic membranous nephropathy (IMN) renal replacement treatment (RRT) total renal chronicity score renal survival Introduction Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in non-diabetic adults, accounting for approximately one-third of all biopsied cases of nephrotic syndrome. MN should be suspected in all adult patients presenting with features of nephrotic syndrome such as unexplained proteinuria, hypoalbuminemia, edema and weight gain. Renal biopsy is required to make a diagnosis of MN. In patients with contraindications for renal biopsy, MN can be diagnosed by serological tests in patients without biopsy due to the identification of target antigens and the specificity of serological tests for phospholipase-A2 receptor (PLA2R) antibodies. [ 1 ] Approximately 80% of MN cases are idiopathic membranous nephropathy (IMN) or primary MN (pMN) and 20% are secondary to systemic disease (sMN). IMN represents 20–37% of nephrotic syndrome cases and approximately 40% of nephrotic syndrome cases in adults over 60 years of age [ 2 ]. MN can occur in all ethnic and racial groups and genders. However, IMN is more common in white men over 40 years of age. MN in young women increase the likelihood of systemic lupus erythematosus (SLE) [ 3 ]. In pMN, deposition of IgG4 subclass of IgG is dominant, whereas in secondary MN, deposition of other subclasses of IgG is predominant [ 4 ]. In MN, immunosuppressive therapies and general preventive approaches (including blood pressure control, minimization of proteinuria by inhibition of the renin-angiotensin system, treatment of dyslipidemia and anticoagulation in some patients) are recommended for all patients. Other aspects of treatment include dietary sodium restriction, diuretics for edema control and adequate nutritional support [ 5 ]. The exact pathogenesis of MN is still unknown. Moreover, the course of MN is highly variable, approximately one-third of patients achieve spontaneous remission, one-third have persistent proteinuria and the other third progress to end-stage renal disease (ESRD). Clinical studies demonstrated that male sex, advanced age (> 50 years old), hypertension, persistent nephrotic range proteinuria and elevated serum creatinine levels at the time of renal biopsy are associated with poor outcomes [ 6 – 9 ]. The total renal chronicity score, developed based on the basis of the consensus report for glomerular disease, was proposed by an international collaboration in 2017 and is also called the Mayo Clinic Chronicity Score (MCCS). The total renal chronicity score was designed to provide a systematic, standardized and semi-quantitative assessment of the extent and degree of renal chronicity, help in prognostic assessment and guide treatment. Specifically, glomerulosclerosis, tubular atrophy and interstitial fibrosis are scored from 0 to 3 according to the percentage involvement of each compartment ( 50%), and arteriosclerosis ranges from 0 to 1 according to the intima-media thickness. Four grades (minimal, mild, moderate and severe) subsequently derived from the total renal chronicity score could more intuitively indicate different degrees of chronic lesions. [ 10 ] Methods Study design and patient selection The study was performed retrospectively at a single center on patients over 16 years of age who were admitted to our hospital between January 2009 and February 2019. Patients who underwent renal biopsy and were diagnosed with MN by the pathology department as a result of the biopsy were included in the study. Patients whose renal biopsies were evaluated by the pathology department and diagnosed with MN were grouped into IMN and sMN groups. The grouping of primary and secondary samples was performed on immunofluorescence staining results of renal biopsies, the presence or absence of IgG4 accumulation, serological tests and autoantibody tests obtained from serum blood biochemistry, and imaging tests performed for possible malignancy. Patients who were diagnosed with IMN at the end of the investigations were included in the study. The exclusion criteria were as follows: (1) patients with other renal diseases or secondary membranous nephropathy; (2) age <16 years; (3) patients no follow-up for 5 years or until renal outcome; (4) steroid and/or immunosuppressant use within 6 months prior to biopsy; (5) renal histopathology IgG and C3 staining via immunofluorescence microscopy, tubular atrophy, glomerulosclerosis, interstitial fibrosis and atherosclerosis not examined or evaluated (6) patients who died of non-renal causes. Data collection Demographic (age, gender), laboratory and pathological data were obtained from the hospital registration system. Serum creatinine, serum albumin and protein/creatinine ratio in spot urine, protein excretion in 24-hour urine were analyzed. Patients were divided into groups according to their proteinuria levels as follows; (1) 3.5-8 g/day, (3) >8 g/day. The patients were divided into two groups according to their serum albumin levels as follows ;3g/dl. Whether the patients received immunosuppressive therapy and other conservative treatments at follow-up were noted. Kidney histopathology IgG and C3 staining on immunofluorescence microscopy were examined. Tubular atrophy, glomerulosclerosis, interstitial fibrosis and atherosclerosis were noted on light microscopy. The scoring and grading of renal chronicity was performed according to the chronicity score defined by the Mayo clinic. Specifically, glomerulosclerosis, tubular atrophy and interstitial fibrosis scores ranged between 0 to 3 (50% involvement of tissue compartments, respectively), and arteriosclerosis was scored as 0 when the baseline thickness was less than the medial thickness and 1 otherwise. Individual scores were then summed and chronicity was graded as follows: minimal; 0-1, mild; 2-4, moderate; 5-7, and ≥ 8, severe. Given the relatively low rate of severe chronic pathological damage in IMN patients and the limited sample size, chronicity was divided into 2 graded groups to achieve better efficiency, and the groups were made as follows; 0-1, minimal chronicity and 2-10, non-minimal chronicity Patient follow-up was performed at 6, 12, 24, 36 and 60 months after renal biopsy. Serum creatinine, serum protein, serum albumin and 24-hour proteinuria were recorded at these visits. Outcome The outcome was doubling of serum creatinine or renal replacement treatment (RRT). Patients requiring hemodialysis, peritoneal dialysis or renal transplantation were defined as patients receiving RRT. In these controls, if serum creatinine doubled or RRT was needed, at least 3 months of follow-up were performed for the persistence of this condition and patients with persistent chronicity were recorded. Renal survival was defined as at least a two-fold increase in serum creatinine from baseline and the need for RRT. Statistical Analysis: In the study, descriptive statistics of categorical data were presented as number and percentage and descriptive statistics of continuous variables were presented as mean, standard deviation, minimum and maximum values. Comparison of continuous variables between two groups was evaluated by Mann Whitney-U test. Differences between categorical variables were evaluated by chi-square test. Renal survival rate was calculated by Kaplan-Meier method. The difference in survival rates between groups was analyzed by log-rank test. The association of covariates with renal survival was assessed using the Cox proportional hazards model, and the hazard ratio (HR) and 95% confidence interval were obtained. Analyses were performed using IBM SPSS statistics (version 21.0, Chicago, IL, USA). p < 0.05 was considered statistically significant. Results A total of 50 patients were included in the study. These patients had regular follow-up for at least as long as they achieved renal survival or up to a total of 60 months. Characteristics of 50 patients at the time of renal biopsy mean age 48 years (SD:13) and 38 male (76%) patients were found. In the cohort, baseline 24-hour proteinuria median 7950 mg/day (IQR: 6109), serum creatinine means 1.07mg/dl (SD: 0.8), serum albumin means 2.78g/dl (SD: 0.7) were found. Proteinuria >8g/day was found in 24 patients (48%). Patients with serum albumin level <3g/dl were 29 and comprised 58% of the cohort. The total renal chronicity score on renal biopsy was calculated and found to be minimal (n:30), mild (n:17), moderate (n:3) and severe (n:0) in the cohort. Mild, moderate and severe chronic changes were combined and grouped into a single group as non-minimal changes. 30 (%60) patients had minimal changes and 20 (%40) patients had non-minimal changes. (Table 1.) In our study, the outcome was doubling of serum creatinine or RRT and we found that this was realized in 20 patients. There were 30 patients with stable renal function (first group) and 20 patients two-fold increase in serum creatinine or RRT (second group). Patients in the second group were older than patients in the first group (first group means (SD) 44.5 (11.9, second group means (SD) 53.85 (12.2)), which was statistically significant (p:0.01). 24-hour proteinuria was significantly different between the two groups and this was statistically significant (p=0.01). Serum albumin was 2.3g/dl (SD:0.5) in the second group and was significantly lower than the first group (p<0.001). Serum albumin level was <3g/dl in 18 (90%) patients in the second group, which was statistically higher than in the first group (p<0.001). Patients with minimal chronic changes on renal biopsy were 29 (96.7%) in the first group and this was statistically significant (p<0.001). We found that 29 of the patients received immunosuppressive treatments and 21 did not receive immunosuppressive treatment and were followed up with conservative treatments. In the first group, we found that immunosuppressive treatments were used in 19 (63.3%) of the patients. In the second group, 10 (50%) of the patients received immunosuppressive treatment and the other 10 patients did not. When the two groups were compared in terms of renal survival, although numerically those receiving immunosuppressive therapy had a higher rate of stable renal function, it did not reach statistical significance (p=0.349). A time sensitive univariate analysis was performed based on the time of two-fold increase in serum creatinine or RRT at 5 years follow up. All parameters were analyzed individually and results were obtained by Cox regressions analysis. The results showed that age, serum creatinine, serum albumin, serum albumin grade and total chronicity grade were statistically significant risk factors for renal survival. Although the proteinuria grade was thought to predict the development of renal survival, it did not reach statistical significance (p=0.13). Univariate analysis results are given in Table 2. A multivariate regression model was constructed and used to confirm associations demonstrated by univariate analyses. Serum creatinine, serum albumin and total renal chronicity score grade at the time of renal biopsy was found to be an independent risk factor for the development of renal survival [serum creatinine (HR:2.38, CI: 1.37-4.11, p=0.02), serum albumin (HR:0.43, CI:0.23-0.8, p=0.008) and total renal chronicity score grade (HR:14.4, CI:3.2-64.6, p<0.001)]. Multivariate analysis results are given in Table 2. Discussion In our retrospective single center study, we analyzed the demographic, laboratory and pathology data of the patients for renal survival at 5-year follow-up. In our study, patients who required a two-fold increase in serum creatinine or RRT for renal survival were detected in 20 patients (40%). In the study with similar renal survival measures to our study, doubling of serum creatinine and development of ESRD occurred in 22 patients (13%) at a median follow-up of 123 months. [ 11 ]. It should be kept in mind that 65 (28%) of the 231 patients in the cohort in this study had subnephrotic proteinuria (< 3.5 g/day). In our study, 4 (8%) patients had subnephrotic proteinuria, and for this reason we may have had a higher renal outcome. Renal survival in terms of age at the time of renal biopsy was statistically significant and significantly higher in the second group. Wei et al. showed that age at diagnosis was a risk factor for glomerulosclerosis in IMN patients and glomerulosclerosis was associated with poor renal survival. [ 12 ] In our study, we used the chi-square test for the association between 24-hour proteinuria and poor renal survival, but this was not statistically significant in univariate analysis. In the study of Yamaguchi et al. on the effect of urinary protein excretion on renal prognosis in IMN patients, it was reported that low proteinuria was significant in terms of 30% reduction in eGFR, but the multivariate model was not significant (p = 0.06) [ 13 ]. In another study, it was determined by Kaplan-Meier analysis that survival was less with an increase in the degree of proteinuria in terms of ESRD or death with a 50% decrease in eGFR (p:0.0039) [ 14 ]. When we grouped proteinuria, we found that daily excretion > 8g may be associated with renal survival in univariate analysis, but this did not reach statistical significance (p = 0.07). We found that serum creatinine level at the time of renal biopsy is an independent risk factor for renal survival. In a previous study, serum creatinine level was not found to be significant for a 30% decrease in eGFR in renal survival in a multivariate analysis (HR 2.00, CI 0.45–8.84, p = 361). [ 13 ] In another study, in a multivariate analysis of serum creatinine adjusted for age and gender albumin concentration, a two-fold increase in creatinine or ESRD was statistically significant as a group (HR 12.40, CI 1.17–131.6, p = 0.037). Because of the group effect in this study, it is not possible to talk about serum creatinine alone. [ 11 ]. We found that patients with both serum albumin and albumin levels lower than 3g/dl had worse renal survival (p < 0.001). Serum albumin level was not found to be an independent risk factor in our multivariate model. In recent study, a 50% reduction in renal survival, ESRD or RRT scales were determined in terms of renal survival and the relationship between low albumin level and renal survival was found to be significant in univariate analysis (p < 0.001). [ 15 ] The impact of the total renal chronicity score on renal survival in patients with IMN other than glomerulonephritis was recently studied. Total renal chronicity score independently predicted renal survival [odds ratio (OR): 1.562, CI 1.073–2.273, P = 0.020], but non-minimal chronicity was also found to be an independent risk factor for renal survival (OR: 3.170, 95% CI 1.040–9.659, p = 0.042). [ 16 ] In our study, having a non-minimal total renal chronicity score grade was found to be an independent risk factor in our multivariate model, supporting the existing knowledge (HR 32.0, CI 3.6-280.6, p = 0.02). In our study, the effect of immunosuppressive therapy on renal survival was not found to be significant. However, in the light of current knowledge, it should be kept in mind that immunosuppressive therapy may improve renal survival in patients with low albumin (especially 8g/day) and high total renal chronicity score (presence of non-minimal chronic change grade) on renal biopsy at the time of diagnosis. In a recent study showed that immunosuppressive therapy was effective in preventing the development of ESRD [ 15 ]. The effect of immunosuppressive therapy on survival may not have been reached due to the retrospective nature of our study, patient compliance, small number of patients and advanced age of our patients. The limitations of our study are that it was retrospective, single center and limited number of patients. In conclusion, we found that serum creatinine, serum albumin (especially < 3g/dl), age, and non-minimal total renal chronicity score were associated with a significantly increased risk of two-fold increase creatinine level or need for RRT at 5-year follow-up. Furthermore, serum creatinine level and total renal chronicity score grade were independent risk factors for renal survival. Therefore, it should be kept in mind that patients with these risk factors are associated with poor renal survival at the time of diagnosis or renal biopsy, and patients should be followed with appropriate treatment and follow-up. Declarations Author contributions: This study is based on the specialization thesis of the corresponding author Hasan Kocaayan. The work was project designed by Yusuf Uzum and Zeki Soypacacı. Hasan Kocaayan collected the samples and summarized the data and wrote the original draft of the study. Fulya Cakalagaoglu examined and scored the renal biopsies. Hasan Kocaayan processed the data and performed the statistical analysis. Yusuf Uzum, Zeki Soypacaci and Ibrahim Ertekin revised and edited the final draft. Funding: None. Data availability: The data that support the findings of this study are available from the corresponding author, (Hasan Kocaayan), upon reasonable request. Declarations: Conflicts of interest None declared. Ethical approval : The study protocol was approved by the Izmir Katip Celebi University Clinical Research Ethics Committee (decision number 621) and performed as per the Helsinki Declaration. Acknowledgements: I would like to thank my esteemed professors who supported me in my thesis and my beloved wife Selin Kocaayan. References Bobart SA, De Vriese AS, Pawar AS et al. Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies. Kidney Int 2019; 95: 429–438. Cattran DC, Brenchley PE. Membranous nephropathy: integrating basic science into improved clinical management. Kidney Int 2017; 91: 566–574. Hladunewich MA, Troyanov S, Calafati J, Cattran DC. The Natural History of the Non-Nephrotic Membranous Nephropathy Patient. Clinical Journal of the American Society of Nephrology 2009; 4: 1417–1422. Ohtani H, Wakui H, Komatsuda A et al. Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy. Nephrology Dialysis Transplantation 2004; 19: 574–579. Floege J, Barbour SJ, Cattran DC et al. Management and treatment of glomerular diseases (part 1): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2019; 95: 268–280. Roccatello D, Sciascia S, Di Simone D et al. New insights into immune mechanisms underlying response to Rituximab in patients with membranous nephropathy: A prospective study and a review of the literature. Autoimmun Rev 2016; 15: 529–538. Shiiki H, Saito T, Nishitani Y et al. Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan. Kidney Int 2004; 65: 1400–1407. Zuo K, Wu Y, Li S-J, Xu F, Zeng C-H, Liu Z-H. Long-term outcome and prognostic factors of idiopathic membranous nephropathy in the Chinese population. Clin Nephrol 2013; 79: 445–453. Chen X, Chen Y, Ding X et al. Baseline proteinuria level is associated with prognosis in idiopathic membranous nephropathy. Ren Fail 2019; 41: 363–369. Sethi S, D’Agati VD, Nast CC et al. A proposal for standardized grading of chronic changes in native kidney biopsy specimens. Kidney Int 2017; 91: 787–789. Huh H, Lee H, Lee JP et al. Factors affecting the long-term outcomes of idiopathic membranous nephropathy. BMC Nephrol 2017; 18: 104. Wei C, He Y, Li T et al. Glomerulosclerosis predicts poor renal outcome in patients with idiopathic membranous nephropathy. Int Urol Nephrol 2021; 53: 505–514. Yamaguchi M, Ando M, Katsuno T, Tsuboi N, Maruyama S. Urinary protein and renal prognosis in idiopathic membranous nephropathy: a multicenter retrospective cohort study in Japan. Ren Fail 2018; 40: 435–441. Chen X, Chen Y, Ding X et al. Baseline proteinuria level is associated with prognosis in idiopathic membranous nephropathy. Ren Fail 2019; 41: 363–369. Li W, Cen J, Qi D et al. Effects of immunosuppressive therapy on renal prognosis in primary membranous nephropathy. BMC Nephrol 2024; 25: 377. Ren W, Sun J, Zhang L, He W, Guo Z, Bian Q. Significance of the total renal chronicity score in predicting renal outcome in PLA2R-associated membranous nephropathy. J Nephrol 2024; 37: 1051–1061. Tables Table 1. Baseline (at the time of renal biopsy) characteristic of patients All Patients (50) Stable Renal Function (30) Two-fold increase in serum creatinine or RRT (20) p Age, mean (SD) years 48.24 (12.8) 44.5 (11.9) 53.85 (12.2) 0.01 Gender, male, n (%) 38 (76.0) 21 (70.0) 17 (85.0) 0.22 Proteinuria (24 h urine) (median IQR mg/day) 7950 (6109) 6900 (5825) 11000 (7225) 0.01 Serum creatinine, mean (SD) mg/dl 1.07 (0.8) 0.81 (0.3) 1.47 (1.1) 0.056 Serum albumin, mean (SD) g/dl 2.78 (0.7) 3.1 (0.7) 2.3 (0.5) <0.001 Presence of immunosuppressive therapy, n (%) 29 (58) 19 (63.3) 10 (%50) 0.349 Proteinuria grade n (%) 3.5-8g/day >8g /day 4 (8.0) 22 (44.0) 24 (48.0) 4 (13.3) 15 (50.0) 11 (36.7) 0 (0.0) 7 (35.0) 13 (65.0) 0.07 Serum albumin grade n (%) 3g/dl 29 (58.0) 21 (42.0) 11 (36.7) 19 (63.3) 18 (90.0) 2 (10.0) <0.001 Total renal chronicity score grade n(%) Minimal chronic changes Non-minimal chronic changes* 30 (60.0) 20 (40.0) 29 (96.7) 1 (3.3) 1 (5.0) 19 (95.0) <0.001 SD: Standard deviation, IQR: interquartile-range, n: number of patients, *Mild (n:17), moderate(n:3) and severe (n:0) chronic changes were combined and grouped as a single group as non-minimal changes. Analysis of variance or the chi-square test was used to compare the two groups (Stabil renal function and Two-fold increase in serum creatinine or RRT). p <0 .05 was shown in bold. Table 2. Survival analysis regarding the risk factors for Two-fold increase in serum creatinine or RRT at 5 years follow up Univariate analysis Multivariate analysis Predictors of At the time of renal biopsy HR (%95 CI) p* HR (%95 CI) p* Age 1.04 (1.00-1.08) 0.023 1.01 (0.97-1.05) 0.51 Proteinuria (24 h urine) 1.0 (1.00-1.00) 0.92 Serum creatinine 3.05 (1.79-5.19) <0.001 2.38 (1.37-4.11) 0.02 Serum albumin 0.31 (0.16-0.61) 0.001 0.43 (0.23-0.8) 0.008 Proteinuria grade 0.32 (0.73-1.43) 0.13 Serum albumin grade 0.11 (0.02-0.47) 0.003 Total renal chronicity score grade+ 50.7 (6.74-381.95) <0.001 14.4 (3.2-64.6) <0.001 * P value from Log rank by Cox-regression analysis p <0 .05 was shown in bold. HR: Hazard Ratio, CI: Confidence Interval. + Divided into two groups, minimal and non-minimal. Mild (n:17), moderate(n:3) and severe (n:0) chronic changes were combined and grouped as a single group as non-minimal changes Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5968053","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":414704817,"identity":"4074e048-47aa-4e37-9db4-a4b198cd45ee","order_by":0,"name":"Hasan Kocaayan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYBACAzB5AMatAGJm5gZStJwBaWEkRQtjG5jEr8Wc/fjDzwVnbOT5288Yfi6cVxvN3w7U8qNiG04tlj05xtIzbqQZzjgDZMzcdjx3xmHGBsaeM7dxO+xADoM0z4fDCQwHcgykebcdy20AamFmbMOj5fzzx79BWuTPvzH+zTvnWO58glpuJJhJ89w4nGBwI8dMmrehJncDYS1vzKx5zqQZbrzxrMya59iB3I1ALQfx+uV8+uPbPMds5OXOJ2++zVNTlzvv/OGDD35U4NaCBDhAcXQYzDxAjHogYH8AJOqIVDwKRsEoGAUjCQAAJ35gweoyz8UAAAAASUVORK5CYII=","orcid":"","institution":"Izmir Katip Celebi University School of Medicine, Izmir Ataturk Education and Research Hospital Internal Medicine Clinic","correspondingAuthor":true,"prefix":"","firstName":"Hasan","middleName":"","lastName":"Kocaayan","suffix":""},{"id":414704818,"identity":"f55a93c7-807d-488c-b496-192b667e1ebc","order_by":1,"name":"Yusuf Uzum","email":"","orcid":"","institution":"Izmir Katip Celebi University School of Medicine, Izmir Ataturk Education and Research Hospital Internal Medicine Clinic","correspondingAuthor":false,"prefix":"","firstName":"Yusuf","middleName":"","lastName":"Uzum","suffix":""},{"id":414704819,"identity":"36918483-f2c9-4870-b1cc-81bf4302866b","order_by":2,"name":"Ibrahim Ertekin","email":"","orcid":"","institution":"Izmir Katip Celebi University School of Medicine, Izmir Ataturk Education and Research Hospital Internal Medicine Clinic","correspondingAuthor":false,"prefix":"","firstName":"Ibrahim","middleName":"","lastName":"Ertekin","suffix":""},{"id":414704820,"identity":"e4c20508-72cb-4fdb-9d45-48d70723ca26","order_by":3,"name":"Fulya Cakalagaoglu","email":"","orcid":"","institution":"Izmir Katip Celebi University School of Medicine, Izmir Ataturk Education and Research Hospital Internal Medicine Clinic","correspondingAuthor":false,"prefix":"","firstName":"Fulya","middleName":"","lastName":"Cakalagaoglu","suffix":""},{"id":414704821,"identity":"28a0057f-cbbc-4306-b8b2-510d6d7ce0d5","order_by":4,"name":"Zeki Soypacaci","email":"","orcid":"","institution":"Izmir Katip Celebi University School of Medicine, Izmir Ataturk Education and Research Hospital Internal Medicine Clinic","correspondingAuthor":false,"prefix":"","firstName":"Zeki","middleName":"","lastName":"Soypacaci","suffix":""}],"badges":[],"createdAt":"2025-02-05 18:38:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5968053/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5968053/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78279977,"identity":"4718fd0e-07ad-482b-89cd-b8ba53615167","added_by":"auto","created_at":"2025-03-11 15:01:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":651479,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5968053/v1/e7c78db7-1eae-4225-9d19-ca7df90740f7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Could the total renal chronicity score at renal biopsy and baseline creatinine be predictive of long-term renal survival in primary membranous nephropathy patients?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMembranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in non-diabetic adults, accounting for approximately one-third of all biopsied cases of nephrotic syndrome. MN should be suspected in all adult patients presenting with features of nephrotic syndrome such as unexplained proteinuria, hypoalbuminemia, edema and weight gain. Renal biopsy is required to make a diagnosis of MN. In patients with contraindications for renal biopsy, MN can be diagnosed by serological tests in patients without biopsy due to the identification of target antigens and the specificity of serological tests for phospholipase-A2 receptor (PLA2R) antibodies. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eApproximately 80% of MN cases are idiopathic membranous nephropathy (IMN) or primary MN (pMN) and 20% are secondary to systemic disease (sMN). IMN represents 20\u0026ndash;37% of nephrotic syndrome cases and approximately 40% of nephrotic syndrome cases in adults over 60 years of age [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. MN can occur in all ethnic and racial groups and genders. However, IMN is more common in white men over 40 years of age. MN in young women increase the likelihood of systemic lupus erythematosus (SLE) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In pMN, deposition of IgG4 subclass of IgG is dominant, whereas in secondary MN, deposition of other subclasses of IgG is predominant [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In MN, immunosuppressive therapies and general preventive approaches (including blood pressure control, minimization of proteinuria by inhibition of the renin-angiotensin system, treatment of dyslipidemia and anticoagulation in some patients) are recommended for all patients. Other aspects of treatment include dietary sodium restriction, diuretics for edema control and adequate nutritional support [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe exact pathogenesis of MN is still unknown. Moreover, the course of MN is highly variable, approximately one-third of patients achieve spontaneous remission, one-third have persistent proteinuria and the other third progress to end-stage renal disease (ESRD). Clinical studies demonstrated that male sex, advanced age (\u0026gt;\u0026thinsp;50 years old), hypertension, persistent nephrotic range proteinuria and elevated serum creatinine levels at the time of renal biopsy are associated with poor outcomes [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe total renal chronicity score, developed based on the basis of the consensus report for glomerular disease, was proposed by an international collaboration in 2017 and is also called the Mayo Clinic Chronicity Score (MCCS). The total renal chronicity score was designed to provide a systematic, standardized and semi-quantitative assessment of the extent and degree of renal chronicity, help in prognostic assessment and guide treatment. Specifically, glomerulosclerosis, tubular atrophy and interstitial fibrosis are scored from 0 to 3 according to the percentage involvement of each compartment (\u0026lt;\u0026thinsp;10%, 10\u0026ndash;25, 26\u0026ndash;50 and \u0026gt;\u0026thinsp;50%), and arteriosclerosis ranges from 0 to 1 according to the intima-media thickness. Four grades (minimal, mild, moderate and severe) subsequently derived from the total renal chronicity score could more intuitively indicate different degrees of chronic lesions. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and patient selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was performed retrospectively at a single center on patients over 16 years of age who were admitted to our hospital between January 2009 and February 2019. Patients who underwent renal biopsy and were diagnosed with MN by the pathology department as a result of the biopsy were included in the study. Patients whose renal biopsies were evaluated by the pathology department and diagnosed with MN were grouped into IMN and sMN groups. The grouping of primary and secondary samples was performed on immunofluorescence staining results of renal biopsies, the presence or absence of IgG4 accumulation, serological tests and autoantibody tests obtained from serum blood biochemistry, and imaging tests performed for possible malignancy. Patients who were diagnosed with IMN at the end of the investigations were included in the study. The exclusion criteria were as follows: (1) patients with other renal diseases or secondary membranous nephropathy; (2) age \u0026lt;16 years; (3) patients no follow-up for 5 years or until renal outcome; (4) steroid and/or immunosuppressant use within 6 months prior to biopsy; (5) renal histopathology IgG and C3 staining via immunofluorescence microscopy, tubular atrophy, glomerulosclerosis, interstitial fibrosis and atherosclerosis not examined or evaluated \u0026nbsp;(6) patients who died of non-renal causes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDemographic (age, gender), laboratory and pathological data were obtained from the hospital registration system. Serum creatinine, serum albumin and protein/creatinine ratio in spot urine, protein excretion in 24-hour urine were analyzed. Patients were divided into groups according to their proteinuria levels as follows; (1) \u0026lt;3.5 g/day, (2) \u0026gt;3.5-8 g/day, (3) \u0026gt;8 g/day. The patients were divided into two groups according to their serum albumin levels as follows ;\u0026lt;3g/dl and \u0026gt;3g/dl. Whether the patients received immunosuppressive therapy and other conservative treatments at follow-up were noted.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eKidney histopathology IgG and C3 staining on immunofluorescence microscopy\u0026nbsp;were examined. Tubular atrophy, glomerulosclerosis, interstitial fibrosis and atherosclerosis were noted on light microscopy. The scoring and grading of renal chronicity was performed according to the chronicity score defined by the Mayo clinic. Specifically, glomerulosclerosis, tubular atrophy and interstitial fibrosis scores ranged between 0 to 3 (\u0026lt;10, 10-25, 26-50 and \u0026gt;50% involvement of tissue compartments, respectively), and arteriosclerosis was scored as 0 when the baseline thickness was less than the medial thickness and 1 otherwise. Individual scores were then summed and chronicity was graded as follows: minimal; 0-1, mild; 2-4, moderate; 5-7, and \u0026ge; 8, severe. Given the relatively low rate of severe chronic pathological damage in IMN patients and the limited sample size, chronicity was divided into 2 graded groups to achieve better efficiency, and the groups were made as follows; 0-1, minimal chronicity and 2-10, non-minimal chronicity\u003c/p\u003e\n\u003cp\u003ePatient follow-up was performed at 6, 12, 24, 36 and 60 months after renal biopsy. Serum creatinine, serum protein, serum albumin and 24-hour proteinuria were recorded at these visits.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe outcome was doubling of serum creatinine or renal replacement treatment (RRT). Patients requiring hemodialysis, peritoneal dialysis or renal transplantation were defined as patients receiving RRT. \u0026nbsp;In these controls, if serum creatinine doubled or RRT was needed, at least 3 months of follow-up were performed for the persistence of this condition and patients with persistent chronicity were recorded. Renal survival was defined as at least a two-fold increase in serum creatinine from baseline and the need for RRT.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the study, descriptive statistics of categorical data were presented as number and percentage and descriptive statistics of continuous variables were presented as mean, standard deviation, minimum and maximum values. Comparison of continuous variables between two groups was evaluated by Mann Whitney-U test. Differences between categorical variables were evaluated by chi-square test. Renal survival rate was calculated by Kaplan-Meier method. The difference in survival rates between groups was analyzed by log-rank test. The association of covariates with renal survival was assessed using the Cox proportional hazards model, and the hazard ratio (HR) and 95% confidence interval were obtained. \u0026nbsp;Analyses were performed using IBM SPSS statistics (version 21.0, Chicago, IL, USA). p \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 50 patients were included in the study. These patients had regular follow-up for at least as long as they achieved renal survival or up to a total of 60 months. Characteristics of 50 patients at the time of renal biopsy mean age 48 years (SD:13) and 38 male (76%) patients were found. In the cohort, baseline 24-hour proteinuria median 7950 mg/day (IQR: 6109), serum creatinine means 1.07mg/dl (SD: 0.8), serum albumin means 2.78g/dl (SD: 0.7) were found. Proteinuria \u0026gt;8g/day was found in 24 patients (48%). Patients with serum albumin level \u0026lt;3g/dl were 29 and comprised 58% of the cohort. The total renal chronicity score on renal biopsy was calculated and found to be minimal (n:30), mild (n:17), moderate (n:3) and severe (n:0) in the cohort. Mild, moderate and severe chronic changes were combined and grouped into a single group as non-minimal changes. 30 (%60) patients had minimal changes and 20 (%40) patients had non-minimal changes. (Table 1.)\u003c/p\u003e\n\u003cp\u003eIn our study, the outcome was doubling of serum creatinine or RRT and we found that this was realized in 20 patients. There were 30 patients with stable renal function (first group) and 20 patients two-fold increase in serum creatinine or RRT (second group). \u0026nbsp;Patients in the second group were older than patients in the first group (first group means (SD) 44.5 (11.9, second group\u0026nbsp;means (SD) 53.85 (12.2)), which was statistically significant (p:0.01). 24-hour proteinuria was significantly different between the two groups and this was statistically significant (p=0.01). Serum albumin was 2.3g/dl (SD:0.5) in the second group and was significantly lower than the first group (p\u0026lt;0.001). Serum albumin level was \u0026lt;3g/dl in 18 (90%) patients in the second group, which was statistically higher than in the first group (p\u0026lt;0.001). Patients with minimal chronic changes on renal biopsy were 29 (96.7%) in the first group and this was statistically significant (p\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eWe found that 29 of the patients received immunosuppressive treatments and 21 did not receive immunosuppressive treatment and were followed up with conservative treatments. In the first group, we found that immunosuppressive treatments were used in 19 (63.3%) of the patients. In the second group, 10 (50%) of the patients received immunosuppressive treatment and the other 10 patients did not. When the two groups were compared in terms of renal survival, although numerically those receiving immunosuppressive therapy had a higher rate of stable renal function, it did not reach statistical significance (p=0.349).\u003c/p\u003e\n\u003cp\u003eA time sensitive univariate analysis was performed based on the time of two-fold increase in serum creatinine or RRT at 5 years follow up. All parameters were analyzed individually and results were obtained by Cox regressions analysis. The results showed that age, serum creatinine, serum albumin, serum albumin grade and total chronicity grade were statistically significant risk factors for renal survival. Although the proteinuria grade was thought to predict the development of renal survival, it did not reach statistical significance (p=0.13). Univariate analysis results are given in Table 2.\u003c/p\u003e\n\u003cp\u003eA multivariate regression model was constructed and used to confirm associations demonstrated by univariate analyses. Serum creatinine, serum albumin and total renal chronicity score grade at the time of renal biopsy was found to be an independent risk factor for the development of renal survival [serum creatinine (HR:2.38, CI: 1.37-4.11, p=0.02), serum albumin (HR:0.43, CI:0.23-0.8, p=0.008) and total renal chronicity score grade (HR:14.4, CI:3.2-64.6, p\u0026lt;0.001)]. Multivariate analysis results are given in Table 2.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our retrospective single center study, we analyzed the demographic, laboratory and pathology data of the patients for renal survival at 5-year follow-up. In our study, patients who required a two-fold increase in serum creatinine or RRT for renal survival were detected in 20 patients (40%). In the study with similar renal survival measures to our study, doubling of serum creatinine and development of ESRD occurred in 22 patients (13%) at a median follow-up of 123 months. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. It should be kept in mind that 65 (28%) of the 231 patients in the cohort in this study had subnephrotic proteinuria (\u0026lt;\u0026thinsp;3.5 g/day). In our study, 4 (8%) patients had subnephrotic proteinuria, and for this reason we may have had a higher renal outcome.\u003c/p\u003e \u003cp\u003eRenal survival in terms of age at the time of renal biopsy was statistically significant and significantly higher in the second group. Wei et al. showed that age at diagnosis was a risk factor for glomerulosclerosis in IMN patients and glomerulosclerosis was associated with poor renal survival. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn our study, we used the chi-square test for the association between 24-hour proteinuria and poor renal survival, but this was not statistically significant in univariate analysis. In the study of Yamaguchi et al. on the effect of urinary protein excretion on renal prognosis in IMN patients, it was reported that low proteinuria was significant in terms of 30% reduction in eGFR, but the multivariate model was not significant (p\u0026thinsp;=\u0026thinsp;0.06) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In another study, it was determined by Kaplan-Meier analysis that survival was less with an increase in the degree of proteinuria in terms of ESRD or death with a 50% decrease in eGFR (p:0.0039) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. When we grouped proteinuria, we found that daily excretion\u0026thinsp;\u0026gt;\u0026thinsp;8g may be associated with renal survival in univariate analysis, but this did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.07).\u003c/p\u003e \u003cp\u003eWe found that serum creatinine level at the time of renal biopsy is an independent risk factor for renal survival. In a previous study, serum creatinine level was not found to be significant for a 30% decrease in eGFR in renal survival in a multivariate analysis (HR 2.00, CI 0.45\u0026ndash;8.84, p\u0026thinsp;=\u0026thinsp;361). [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] In another study, in a multivariate analysis of serum creatinine adjusted for age and gender albumin concentration, a two-fold increase in creatinine or ESRD was statistically significant as a group (HR 12.40, CI 1.17\u0026ndash;131.6, p\u0026thinsp;=\u0026thinsp;0.037). Because of the group effect in this study, it is not possible to talk about serum creatinine alone. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe found that patients with both serum albumin and albumin levels lower than 3g/dl had worse renal survival (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Serum albumin level was not found to be an independent risk factor in our multivariate model. In recent study, a 50% reduction in renal survival, ESRD or RRT scales were determined in terms of renal survival and the relationship between low albumin level and renal survival was found to be significant in univariate analysis (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe impact of the total renal chronicity score on renal survival in patients with IMN other than glomerulonephritis was recently studied. Total renal chronicity score independently predicted renal survival [odds ratio (OR): 1.562, CI 1.073\u0026ndash;2.273, P\u0026thinsp;=\u0026thinsp;0.020], but non-minimal chronicity was also found to be an independent risk factor for renal survival (OR: 3.170, 95% CI 1.040\u0026ndash;9.659, p\u0026thinsp;=\u0026thinsp;0.042). [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] In our study, having a non-minimal total renal chronicity score grade was found to be an independent risk factor in our multivariate model, supporting the existing knowledge (HR 32.0, CI 3.6-280.6, p\u0026thinsp;=\u0026thinsp;0.02).\u003c/p\u003e \u003cp\u003eIn our study, the effect of immunosuppressive therapy on renal survival was not found to be significant. However, in the light of current knowledge, it should be kept in mind that immunosuppressive therapy may improve renal survival in patients with low albumin (especially\u0026thinsp;\u0026lt;\u0026thinsp;3g/dl), high creatinine levels, high proteinuria (especially\u0026thinsp;\u0026gt;\u0026thinsp;8g/day) and high total renal chronicity score (presence of non-minimal chronic change grade) on renal biopsy at the time of diagnosis. In a recent study showed that immunosuppressive therapy was effective in preventing the development of ESRD [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The effect of immunosuppressive therapy on survival may not have been reached due to the retrospective nature of our study, patient compliance, small number of patients and advanced age of our patients.\u003c/p\u003e \u003cp\u003eThe limitations of our study are that it was retrospective, single center and limited number of patients.\u003c/p\u003e \u003cp\u003eIn conclusion, we found that serum creatinine, serum albumin (especially\u0026thinsp;\u0026lt;\u0026thinsp;3g/dl), age, and non-minimal total renal chronicity score were associated with a significantly increased risk of two-fold increase creatinine level or need for RRT at 5-year follow-up. Furthermore, serum creatinine level and total renal chronicity score grade were independent risk factors for renal survival. Therefore, it should be kept in mind that patients with these risk factors are associated with poor renal survival at the time of diagnosis or renal biopsy, and patients should be followed with appropriate treatment and follow-up.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e This study is based on the specialization thesis of the corresponding author Hasan Kocaayan. The work was project designed by Yusuf Uzum and Zeki Soypacacı. Hasan Kocaayan collected the samples and summarized the data and wrote the original draft of the study. Fulya Cakalagaoglu examined and scored the renal biopsies. Hasan Kocaayan processed the data and performed the statistical analysis. Yusuf Uzum, Zeki Soypacaci and Ibrahim Ertekin revised and edited the final draft.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNone.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eThe data that support the findings of this study are available from the corresponding author, (Hasan Kocaayan), upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations:\u0026nbsp;\u003c/strong\u003eConflicts of interest None declared.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e: The study protocol was approved by the Izmir Katip Celebi University Clinical Research Ethics Committee (decision number 621) and performed as per the Helsinki Declaration. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eI would like to thank my esteemed professors who supported me in my thesis and my beloved wife Selin Kocaayan.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBobart SA, De Vriese AS, Pawar AS \u003cem\u003eet al.\u003c/em\u003e Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies. Kidney Int 2019; 95: 429\u0026ndash;438.\u003c/li\u003e\n\u003cli\u003eCattran DC, Brenchley PE. Membranous nephropathy: integrating basic science into improved clinical management. Kidney Int 2017; 91: 566\u0026ndash;574.\u003c/li\u003e\n\u003cli\u003eHladunewich MA, Troyanov S, Calafati J, Cattran DC. The Natural History of the Non-Nephrotic Membranous Nephropathy Patient. Clinical Journal of the American Society of Nephrology 2009; 4: 1417\u0026ndash;1422.\u003c/li\u003e\n\u003cli\u003eOhtani H, Wakui H, Komatsuda A \u003cem\u003eet al.\u003c/em\u003e Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy. Nephrology Dialysis Transplantation 2004; 19: 574\u0026ndash;579.\u003c/li\u003e\n\u003cli\u003eFloege J, Barbour SJ, Cattran DC \u003cem\u003eet al.\u003c/em\u003e Management and treatment of glomerular diseases (part 1): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2019; 95: 268\u0026ndash;280.\u003c/li\u003e\n\u003cli\u003eRoccatello D, Sciascia S, Di Simone D \u003cem\u003eet al.\u003c/em\u003e New insights into immune mechanisms underlying response to Rituximab in patients with membranous nephropathy: A prospective study and a review of the literature. Autoimmun Rev 2016; 15: 529\u0026ndash;538.\u003c/li\u003e\n\u003cli\u003eShiiki H, Saito T, Nishitani Y \u003cem\u003eet al.\u003c/em\u003e Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan. Kidney Int 2004; 65: 1400\u0026ndash;1407.\u003c/li\u003e\n\u003cli\u003eZuo K, Wu Y, Li S-J, Xu F, Zeng C-H, Liu Z-H. Long-term outcome and prognostic factors of idiopathic membranous nephropathy in the Chinese population. Clin Nephrol 2013; 79: 445\u0026ndash;453.\u003c/li\u003e\n\u003cli\u003eChen X, Chen Y, Ding X \u003cem\u003eet al.\u003c/em\u003e Baseline proteinuria level is associated with prognosis in idiopathic membranous nephropathy. Ren Fail 2019; 41: 363\u0026ndash;369.\u003c/li\u003e\n\u003cli\u003eSethi S, D\u0026rsquo;Agati VD, Nast CC \u003cem\u003eet al.\u003c/em\u003e A proposal for standardized grading of chronic changes in native kidney biopsy specimens. Kidney Int 2017; 91: 787\u0026ndash;789.\u003c/li\u003e\n\u003cli\u003eHuh H, Lee H, Lee JP \u003cem\u003eet al.\u003c/em\u003e Factors affecting the long-term outcomes of idiopathic membranous nephropathy. BMC Nephrol 2017; 18: 104.\u003c/li\u003e\n\u003cli\u003eWei C, He Y, Li T \u003cem\u003eet al.\u003c/em\u003e Glomerulosclerosis predicts poor renal outcome in patients with idiopathic membranous nephropathy. Int Urol Nephrol 2021; 53: 505\u0026ndash;514.\u003c/li\u003e\n\u003cli\u003eYamaguchi M, Ando M, Katsuno T, Tsuboi N, Maruyama S. Urinary protein and renal prognosis in idiopathic membranous nephropathy: a multicenter retrospective cohort study in Japan. Ren Fail 2018; 40: 435\u0026ndash;441.\u003c/li\u003e\n\u003cli\u003eChen X, Chen Y, Ding X \u003cem\u003eet al.\u003c/em\u003e Baseline proteinuria level is associated with prognosis in idiopathic membranous nephropathy. Ren Fail 2019; 41: 363\u0026ndash;369.\u003c/li\u003e\n\u003cli\u003eLi W, Cen J, Qi D \u003cem\u003eet al.\u003c/em\u003e Effects of immunosuppressive therapy on renal prognosis in primary membranous nephropathy. BMC Nephrol 2024; 25: 377.\u003c/li\u003e\n\u003cli\u003eRen W, Sun J, Zhang L, He W, Guo Z, Bian Q. Significance of the total renal chronicity score in predicting renal outcome in PLA2R-associated membranous nephropathy. J Nephrol 2024; 37: 1051\u0026ndash;1061.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Baseline (at the time of renal biopsy) characteristic of patients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll Patients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStable Renal Function\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTwo-fold increase in serum creatinine or RRT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eAge, mean (SD) years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e48.24 (12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e44.5 (11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e53.85 (12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eGender, male, n (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e38 (76.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e21 (70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e17 (85.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eProteinuria (24 h urine) (median IQR mg/day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e7950 (6109)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e6900 (5825)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e11000 (7225)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eSerum creatinine, mean (SD) mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.07 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.81 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.47 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003e\u0026nbsp;Serum albumin, mean (SD) g/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e2.78 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e3.1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2.3 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003ePresence of immunosuppressive therapy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e29 (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e19 (63.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e10 (%50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.349\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eProteinuria grade n (%)\u003c/p\u003e\n \u003cp\u003e\u0026lt;3.5g/day\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026gt;3.5-8g/day\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026gt;8g /day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (8.0)\u003c/p\u003e\n \u003cp\u003e22 (44.0)\u003c/p\u003e\n \u003cp\u003e24 (48.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (13.3)\u003c/p\u003e\n \u003cp\u003e15 (50.0)\u003c/p\u003e\n \u003cp\u003e11 (36.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003cp\u003e7 (35.0)\u003c/p\u003e\n \u003cp\u003e13 (65.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eSerum albumin grade n (%)\u003c/p\u003e\n \u003cp\u003e\u0026lt;3g/dl\u003c/p\u003e\n \u003cp\u003e\u0026gt;3g/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29 (58.0)\u003c/p\u003e\n \u003cp\u003e21 (42.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (36.7)\u003c/p\u003e\n \u003cp\u003e19 (63.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18 (90.0)\u003c/p\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eTotal renal chronicity score grade n(%)\u003c/p\u003e\n \u003cp\u003eMinimal chronic changes\u003c/p\u003e\n \u003cp\u003eNon-minimal chronic changes*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30 (60.0)\u003c/p\u003e\n \u003cp\u003e20 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29 (96.7)\u003c/p\u003e\n \u003cp\u003e1 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003cp\u003e19 (95.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSD: Standard deviation, IQR: interquartile-range, n: number of patients, *Mild (n:17), moderate(n:3) and severe (n:0) chronic changes were combined and grouped as a single group as non-minimal changes. Analysis of variance or the chi-square test was used to compare the two groups (Stabil renal function and Two-fold increase in serum creatinine or RRT). p \u0026lt;0 .05 was shown in bold.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Survival analysis regarding the risk factors for Two-fold increase in serum creatinine or RRT at 5 years follow up\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePredictors of\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAt the time of renal biopsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (%95 CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (%95 CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e1.04 (1.00-1.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.01 (0.97-1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eProteinuria (24 h urine)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e1.0 (1.00-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eSerum creatinine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e3.05 (1.79-5.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.38 (1.37-4.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.02\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eSerum albumin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0.31 (0.16-0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.43 (0.23-0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eProteinuria grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0.32 (0.73-1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eSerum albumin grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0.11 (0.02-0.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eTotal renal chronicity score grade+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e50.7 (6.74-381.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e14.4 (3.2-64.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* P value from Log rank by Cox-regression analysis p \u0026lt;0 .05 was shown in bold. HR: Hazard Ratio, CI: Confidence Interval. + Divided into two groups, minimal and non-minimal. Mild (n:17), moderate(n:3) and severe (n:0) chronic changes were combined and grouped as a single group as non-minimal changes\u0026nbsp;\u003c/p\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 (IMN), renal replacement treatment (RRT), total renal chronicity score, renal survival","lastPublishedDoi":"10.21203/rs.3.rs-5968053/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5968053/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eRenal survival is important in patients with idiopathic membranous nephropathy (IMN). In this study we investigated the factors affecting renal survival in IMN patients\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis retrospective single center cohort study included patients who were diagnosed with IMN by renal biopsy between January 2009 and February 2019 and had a 5-year follow-up. Age, gender, serum creatinine, serum albumin, 24-hour proteinuria of the patients at the time of renal biopsy were recorded. The total renal chronicity score was calculated from the results of renal biopsy and patients were divided into minimal and non-minimal (including mild, moderate and severe) according to the total chronicity score. Renal survival was defined as at least a two-fold increase in serum creatinine from baseline and the need for renal replacement treatment (RRT).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eTwenty patients (40%) had doubled serum creatinine levels or needed RRT. In univariate analysis, age, serum creatinine, serum albumin, serum albumin grade (\u0026lt;3g/dl) and total renal chronicity grade were found to be risk factors for renal survival. Multivariate Cox regression analysis revealed that the serum creatinine level [hazard ratio (HR) 2.38, confidence interval (CI) 1.37-4.11, p=0.02], serum albumin level (HR 0.43, CI 0.23-0.8, p=0.008) and total renal chronicity score grade (HR 14.4, CI 3.2-64.6, p:\u0026lt;0.001) were independent risk factors for renal survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eLow albumin levels (especially \u0026lt;3g/dl), high serum creatinine levels and high total renal chronicity scores (the presence of non-minimal degree of chronic change) on renal biopsy at the time of diagnosis are predictive of poor renal survival.\u003c/p\u003e","manuscriptTitle":"Could the total renal chronicity score at renal biopsy and baseline creatinine be predictive of long-term renal survival in primary membranous nephropathy patients?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-14 08:32:06","doi":"10.21203/rs.3.rs-5968053/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":"5a947866-2927-417d-9abd-71cfe69985a1","owner":[],"postedDate":"February 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-11T14:53:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-14 08:32:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5968053","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5968053","identity":"rs-5968053","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}