Prognostic Significance of Dynamic Changes in Glomerular C3 Deposition in Membranous Nephropathy

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Prognostic Significance of Dynamic Changes in Glomerular C3 Deposition in Membranous Nephropathy | 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 Prognostic Significance of Dynamic Changes in Glomerular C3 Deposition in Membranous Nephropathy Won-Hee Cho, Byoung-Soo Cho, Hyun-Soon Lee This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6434093/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: Membranous nephropathy (MN) is a primary cause of nephrotic syndrome in adults, with complement activation being a pivotal factor in its pathophysiology. Nevertheless, the prognostic significance of glomerular C3 deposition, particularly in subsequent biopsies, remains unclear. This study evaluates the influence of alterations in C3 deposition on the clinical prognosis of MN following intravenous methylprednisolone (MPD) treatment. Methods: This retrospective study examined 11 patients with histologically confirmed MN who achieved remission following intravenous MPD pulse therapy and subsequently underwent a follow-up kidney biopsy. The patients were categorized according to the presence or absence of glomerular C3 deposition in the follow-up biopsy. Comparative analysis of clinical, laboratory, and histopathological data was conducted between the groups to evaluate treatment response and long-term outcomes. Results: Eight patients exhibited resolution of C3 deposition on follow-up biopsy, whereas three showed persistent C3 deposition. Despite both groups experiencing a notable decrease in proteinuria, persistent C3 deposition was associated with higher recurrence rates and limited histological improvement. Patients with resolved C3 deposition maintained remission over an average follow-up period of 5.3 years, whereas all patients with persistent C3 deposition experienced relapse during follow-up. Conclusions: The intravenous MPD pulse therapy successfully induced remission of MN. Additionally, the disappearance of glomerular C3 deposition following therapy may serve as a prognostic indicator for long-term remission. membranous nephropathy complement C3 glomerular deposition prognosis kidney biopsy remission Figures Figure 1 Figure 2 Figure 3 Introduction Membranous nephropathy (MN) is a primary cause of nephrotic syndrome (NS) in adults and is characterized by subepithelial immune complex deposition along the glomerular capillary walls. MN is categorized into primary and secondary forms based on the origin of these immune complexes. Primary MN is associated with autoantigens such as the M-type phospholipase A 2 receptor (PLA2R), thrombospondin type 1 domain-containing 7A, and other antigens, while secondary MN results from autoimmune diseases (e.g., systemic lupus erythematosus), neoplasms, infections, and medications. The clinical course of primary MN is highly variable, ranging from spontaneous remission to frequent relapse and, in some cases, progression to end-stage kidney disease (ESKD) [ 1 ]. Although anti-PLA2R antibody testing is a useful diagnostic and prognostic tool, approximately 20–30% of patients with MN are seronegative for PLA2R, and antibody status alone does not consistently predict prognosis [ 2 ]. Emerging evidence suggests that complement activation, particularly glomerular C3 deposition, plays a significant role in the pathophysiology and progression of MN [ 3 ]. However, the prognostic significance of C3 deposition—particularly in follow-up biopsies—remains unclear. This study assessed longitudinal changes in glomerular C3 deposition in patients with MN who showed reduced proteinuria following aggressive immunosuppressive treatment. We examined clinical outcomes in patients with and without persistent glomerular C3 deposition on subsequent biopsy to determine the prognostic significance of C3 deposition dynamics. Method Study Population This retrospective study involved patients with histologically confirmed MN, including membranous lupus nephritis (Class V), who received intravenous (IV) methylprednisolone (MPD) pulse therapy and underwent follow-up kidney biopsies at Dr. Cho’s Kidney Clinic between September 1, 2013, and December 31, 2021. Out of 1,649 outpatient kidney biopsies conducted during this period, 31 (1.88%) were histologically diagnosed as MN. Eleven patients (0.67%) achieved complete or partial remission following IV MPD pulse therapy and underwent repeat biopsies. These 11 patients constituted the study cohort (Fig. 1 ). Initial biopsy indications included NS resistant to oral glucocorticoids (n = 6), persistent non-nephrotic-range proteinuria despite oral glucocorticoid therapy (n = 2), and combined proteinuria with hematuria (n = 3). Two patients were eventually diagnosed with membranous lupus nephropathy (WHO Class V), while nine were found to have primary MN upon repeat biopsy analysis. For analysis, patients were categorized into two groups based on the presence or absence of glomerular C3 deposition in follow-up biopsies; eight patients showed no C3 deposition on repeat biopsy, whereas three exhibited persistent glomerular C3 deposition. Histopathological Evaluation The kidney biopsy specimens underwent processing and evaluation at the Korea Pathology Laboratory (Seoul, Korea). Each sample contained a minimum of eight glomeruli. For light microscopy, tissues were fixed in 10% formalin, embedded in paraffin, sectioned at 2–4µm, and stained with hematoxylin-eosin and periodic acid–Schiff. The degree of interstitial fibrosis and tubular atrophy (IFTA) was semi-quantitatively graded on a scale of 0–3 as follows: 0 (normal), 1 (mild, 50%). Immunofluorescence microscopy was conducted on frozen sections using fluorescein isothiocyanate-labeled antibodies against IgG, IgA, IgM, C3, C1q, C4, and fibrinogen. The staining intensity was graded from 0–3: 0 (negative), 1 (weak), 2 (moderate), and 3 (strong). Treatment Protocol All patients received IV MPD pulse therapy at 10–20 mg/kg (maximum 1 g/day) for three consecutive days per cycle. The number of pulse cycles, typically 10–15, was individualized based on pathological findings, laboratory results, and overall clinical status, with a minimum 2-week interval between cycles. Between MPD pulses, patients received oral prednisolone at approximately 0.5 mg/kg daily, which was gradually tapered and discontinued within three months of completing MPD pulse therapy. A follow-up biopsy was performed after completion of therapy to assess post-treatment histopathological changes. Data Collection and Statistical Analysis Clinical and laboratory data were gathered from medical records, including demographics (age and gender), comorbid conditions such as hypertension and diabetes mellitus, laboratory findings (serum protein, albumin, cholesterol, and renal function tests), and detailed histopathological characteristics of each biopsy. Key outcome measures included changes in renal function (serum creatinine level and eGFR), proteinuria, and disease recurrence during the follow-up period. Continuous variables were compared between groups using the Mann–Whitney U test, while categorical variables were compared using Fisher’s exact test. Statistical analyses were conducted using SPSS Statistics version 22 (IBM Corp., Chicago, IL, USA) and GraphPad Prism 8.0 (GraphPad Software, San Diego, CA, USA). Statistical significance was defined as p < 0.05. Results Patient Characteristics Among the 11 patients with pathological features of MN evaluated via repeat biopsy, eight exhibited resolution of glomerular C3 deposition, while three exhibited persistent deposition (Fig. 1 ). The baseline characteristics of the initial and follow-up biopsies are summarized in Table 1 . The median age was higher in the no-C3 group. The distribution of sex and comorbidities (e.g., diabetes mellitus and hypertension) was similar between the groups. Both groups demonstrated stable estimated glomerular filtration rate (eGFR), and the urine protein-to-creatinine ratio (UPCR) significantly improved in all patients. After MPD therapy, NS resolved in six patients—five in the no-C3 group and one in the persistent-C3 group. Table 1 Baseline characteristics of participants at initial and follow-up kidney biopsies. First biopsy Repeat biopsy Variable No C3 deposition (N = 8) C3 deposition (N = 3) P-value No C3 depositon (N = 8) C3 deposition (N = 3) P-value Age 46.0 (33.5–55.0) 36.0 (21.5–44.0) 0.474 47.0 (34.5–56.0) 36.0 (21.5–44.5) 0.474 Gender (male) 4 (50.0%) 2 (66.7%) 1 4 (50.0%) 2 (66.7%) 1 DM 1 (12.5%) 1 (0.0%) 1 0 (0.0%) 1 (66.7%) 1 HTN 7 (87.5%) 3 (100.0%) 1 7 (87.5%) 3 (100.0%) 1 Dyslipidemia 6 (75.0%) 3 (100.0%) 1 6 (75.0%) 3 (100.0%) 1 Fatty liver 1 (12.5%) 1 (33.3%) 0.491 1 (12.5%) 1 (33.3%) 0.491 Gout 1 (12.5%) 0 (0.0%) 1 1 (12.5%) 0 (0.0%) 1 SBP (mmHg) 128.0 (107.8–132.2) 117.0 (114.5–120.5) 0.609 123.5 (119.8–126.0) 118.0 (116.5–119.0) 0.151 DBP (mmHg) 77.5 (70.5–78.2) 70.0 (70.0–71.0) 0.258 77.5 (72.8–80.2) 70.0 (70.0–75.0]) 0.759 BMI (kg/m²) 25.9 (20.8–29.7) 26.2 (21.7–26.9) 0.776 26.2 (20.8–29.5) 26.2 (23.0–26.9) 0.921 Hemoglobin (g/dL) 12.3 (10.8–15.4) 13.0 (12.8–13.8) 0.682 13.5 (11.4–15.3) 13.9 (13.1–14.4) 0.919 Hct (%) 39.0 (32.8–42.5) 39.0 (38.4–41.5) 0.918 42.4 (34.8–43.4) 38.0 (37.5–41.2) 1 WBC (/µL) 7950.0 (6600.0–9625.0) 5000.0 (4250.0–7000.0) 0.194 8350.0 (7575.0–9950.0) 7400.0 (6500.0–8500.0) 0.497 PLT (10³/µL) 313.0 (289.0–340.2) 196.0 (175.5–259.0) 0.194 315.0 (296.8–353.0) 237.0 (217.5–268.0) 0.085 Protein (g/dL) 5.4 (4.4–6.4) 7.2 (5.8–7.8) 0.354 6.5 (6.4–6.9) 7.2 (6.7–7.3) 0.682 Albumin (g/dL) 3.0 (2.5–3.1) 3.4 (2.5–4.0) 0.63 4.0 (4.0–4.2) 4.4 (4.2–4.6) 0.209 Cholesterol (mg/dL) 215.5 (186.0–262.8) 205.0 (187.5–306.5) 0.92 163.5 (155.0–227.5) 130.0 (128.5–154.0) 0.194 Triglyceride (mg/dL) 161.0 (107.8–256.5) 166.0 (151.0–180.5) 1 154.0 (110.5–166.0) 127.0 (112.5–145.0) 0.607 HDL-Chol (mg/dL) 75.9 (53.4–89.7) 39.8 (38.8–49.9) 0.08 70.7 (54.2–89.0) 64.4 (58.2–71.7) 0.776 LDL-Chol (mg/dL) 103.5 (74.2–147.2) 134.0 (118.5–221.5) 0.38 75.5 (48.5–124.2) 52.6 (47.8–59.5) 0.497 Bilirubin (mg/dL) 0.6 (0.4–0.7) 0.7 (0.4–0.9) 0.758 0.8 (0.5–0.9) 0.5 (0.4–0.8) 0.682 ALP (U/L) 57.5 (44.5–71.5) 69.0 (65.0–96.0) 0.194 59.5 (37.0–76.2) 60.0 (54.0–67.5) 0.921 ALT (U/L) 23.0 (16.0–27.5) 20.0 (16.0–26.5) 0.608 21.0 (14.2–32.5) 15.0 (13.5–26.0) 0.758 AST (U/L) 25.0 (23.8–27.5) 28.0 (24.0–29.5) 0.759 21.0 (18.8–25.5) 21.0 (18.5–21.0) 0.758 BUN (mg/dL) 14.9 (14.5–17.2) 18.6 (18.1–19.1) 0.048 13.7 (12.1–18.5) 13.9 (13.4–16.8) 0.63 Creatinine (mg/dL) 0.8 (0.7–1.0) 0.7 (0.7–0.9) 0.759 0.8 (0.8–0.9) 0.8 (0.7–0.9) 0.497 eGFR (MDRD, mL/min/1.73 m²) 89.0 (73.5–101.0) 88.0 (87.5–134.0) 0.63 75.5 (73.8–104.8) 87.0 (86.0–156.0) 0.357 eGFR (CKD-EPI, mL/min/1.73 m²) 88.5 (82.2–90.5) 96.0 (83.0–101.0) 0.63 81.0 (76.0–91.0) 92.0 (86.5–98.5) 0.354 FBS (mg/dL) 94.5 (90.0–104.2) 107.0 (102.0–112.0) 0.26 93.0 (87.8–100.8) 92.0 (90.5–94.5) 1 UPCR (mg/g) 5.2 (3.1–8.4) 1.7 (1.2–8.8) 0.776 0.1 (0.0–0.2) 0.1 (0.1–0.1) 0.921 Urine_RBC(HPF) 0.329 0.491 0 3 (37.5%) 0 (0.0%) 7 (87.5%) 2 (66.7%) 1 ~ 2 1 (12.5%) 1 (33.3%) 1 (12.5%) 0 (0.0%) 3 ~ 5 2 (25.0%) 0 (0.0%) 0 (0.0%) 1 (33.3%) 6 ~ 10 2 (25.0%) 2 (66.7%) 0 (0.0%) 0 (0.0%) Nephrotic syndrome 6 (75.0%) 1 (33.3%) 0.491 0 (0.0%) 0 (0.0%) Abbreviations: BMI, Body Mass Index; FBS, Fasting Blood Sugar; IFTA, interstitial fibrosis tubular atrophy; DBP, diastolic blood pressure; DM, diabetes mellitus; SBP, systolic blood pressure; UPCR, urine protein-to-creatinine ratio; PLT, platelet count; P values obtained from the chi-square test, Fisher’s exact test, or Mann–Whitney U test Histopathological and Therapeutic Findings Histopathologic outcomes varied among the groups. In the resolved-C3 group, follow-up biopsies typically revealed restored podocyte foot processes and resolved subepithelial immune deposits (Fig. 3 E). Conversely, the persistent-C3 group exhibited minimal histological improvement during follow-up. In some instances, there was evidence of ongoing or progressive disease activity despite clinical remission (Table 2 , Fig. 2 ). In the persistent-C3 group, one patient exhibited essentially unchanged glomerular morphology between the initial and follow-up assessments (see Supplementary Table 1 for individual case details). Another patient progressed from lupus nephritis WHO Class IV at baseline to membranous lupus nephritis (WHO Class V) at follow-up (Supplementary Table 1). A third patient developed de novo focal segmental glomerulosclerosis lesions, affecting 27% of the glomeruli by the time of the follow-up biopsy (Fig. 3 ). These findings suggest a more progressive disease course [ 4 ]. Table 2 Histopathological findings from initial and follow-up kidney biopsies. First biopsy Repeat biopsy Variable No C3 depositon (N = 8) C3 deposition (N = 3) P-value No C3 depositon (N = 8) C3 deposition (N = 3) P-value Bx glomerulus (No) 23 (17–26.5) 26 (22–40) 0.539 22.5 (18.8–26.8) 41 (38.5–41) 0.082 Segmental Sclerosis (No) 0 (0–0.2) 1 (0.5–1) 0.402 0 (0–1.5) 3 (1.5–7) 0.315 segmental sclerosis (%)_Initial 0 (0–1.2) 2 (1–3) 0.554 0 (0–9.8) 7 (3.5–17) 0.502 The intensity of IFTA (N, %) (0,1:mild, 2:moderate) 0.849 0.903 Not observed 1 (12.5%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Mild 4 (50.0%) 2 (66.7%) 5 (62.5%) 2 (66.7%) Moderate 3 (37.5%) 1 (33.3%) 3 (37.5%) 1 (33.3%) FPE (N, %) 0.087 0.54 Mild 1 (12.5%) 2 (66.7%) 7 (87.5%) 3 (100.0%) Moderate 0 (0.0%) 0 (0.0%) 1 (12.5%) Severe 7 (87.5%) 1 (33.3%) 0 (0.0%) 0 (0.0%) IgA intensity (N, %) 0.174 0.206 Not observed 6 (75.0%) 0 (0.0%) 7 (87.5%) 2 (66.7%) Ⅰ+ 0 (0.0%) 1 (33.3%) 1 (12.5%) 0 (0.0%) Ⅱ+ 1 (12.5%) 1 (33.3%) 0 (0.0%) 0 (0.0%) Ⅲ+ 0 (0.0%) 1 (33.3%) 0 (0.0%) 0 (0.0%) Ⅳ+ 1 (12.5%) 0 (0.0%) 0 (0.0%) 0 (0.0%) IgG intensity (N, %) 0.102 0.745 Not observed 0 (0.0%) 0 (0.0%) 1 (12.5%) 1 (12.5%) Ⅰ+ 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Ⅱ+ 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Ⅲ+ 0 (0.0%) 1 (33.3%) 4 (50.0%) 0 (0.0%) Ⅳ+ 8 (100.0%) 2 (66.7%) 3 (37.5%) 2 (66.7%) IgM intensity (N, %) 0.125 0.361 Not observed 6 (75.0%) 1 (33.3%) 5 (62.5%) 1 (33.3%) Ⅰ+ 1 (12.5%) 0 (0.0%) 2 (25.0%) 1 (33.3%) Ⅱ+ 0 (0.0%) 1 (33.3%) 1 (12.5%) 1 (33.3%) Ⅲ+ 1 (12.5%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Ⅳ+ 0 (0.0%) 1 (33.3%) 0 (0.0%) 0 (0.0%) C3 (N, %) 0.086 0.002 Not observed 2 (25.0%) 0 (0.0%) 8 (100%) 0 (0.0%) Ⅰ+ 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Ⅱ+ 5 (62.5%) 1 (33.3%) 0 (0.0%) 3 (100%) Ⅲ+ 1 (12.5%) 1 (33.3%) 0 (0.0%) 0 (0.0%) Ⅳ+ 0 (0.0%) 1 (33.3%) 0 (0.0%) 0 (0.0%) C4 (N, %) 0.015 Not observed 8 (100.0%) 1 (33.3%) 8 (100.0%) 3 (100.0%) Ⅰ+ 0 (0.0%) 2 (66.7%) 0 (0.0%) 0 (0.0%) Ⅱ+ 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Ⅲ+ 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Ⅳ+ 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) C1q (N, %) 0.134 0.017 Not observed 7 (87.5%) 1 (33.3%) 8 (100.0%) 1 (33.3%) Ⅰ+ 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Ⅱ+ 0 (0.0%) 1 (33.3%) 0 (0.0%) 1 (33.3%) Ⅲ+ 1 (12.5%) 1 (33.3%) 0 (0.0%) 1 (33.3%) Ⅳ+ 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Abbreviations: Bx, Biopsy; IFTA, interstitial fibrosis tubular atrophy; FPE, foot process effacement. Despite histology differences, both groups experienced clinical benefits from the therapy in terms of reducing proteinuria. IV MPD pulse therapy resulted in a significant decrease in proteinuria in both the resolved-C3 and persistent-C3 groups. The mean UPCR decreased from 5.2 g/g to 0.1 g/g in the resolved-C3 group and from 1.7 g/g to 0.7 g/g in the persistent-C3 group between the initial and follow-up assessments. This improvement was statistically significant within each group, and the post-treatment UPCR values did not show a significant difference between the two groups (p > 0.05) (Table 3 ). No notable differences between the groups in residual segmental sclerosis or IFTA scores upon follow-up were observed (Table 2 ). Renal function remained stable, with serum creatinine levels and eGFR unchanged from baseline in both groups (Table 1 ), indicating the preservation of kidney function in all patients during the observation period. Table 3 Clinical outcomes of participants based on the persistent or absence of C3 deposition in follow-up kidney biopsies. Variable No C3 deposition Median (IQR) C3 deposition Median (IQR) P-Value Biopsy interval (mo) 11 (10.0–16.3) 10 (9.0–10.0) 0.164 Total follow-up duration (mo) 72.5 (45.5–122.8) 43 (41.5–63.0) 0.184 Single MPD dose (mg) 500 (500.0–625.0) 500 (437.5–500.0) 0.407 Total MPD cycles 11.5 (10.0–15.0) 10 (10.0–12.5) 0.819 eGFR at Last follow-up (MDRD, mL/min/1.73 m²) 100.5 (88.0–112.1) 96 (90.5–110.0) 0.921 UPCR at Last follow-up (mg/g) 0.1 (0.1–1.1) 0.7 (0.6–1.8) 0.279 Relapse rate (%) 0 (0.0%) 3 (100.0%) 0.006 Abbreviations: eGFR, estimated glomerular filtration rate; MPD, methylprednisolone; UPCR, urine protein–creatinine ratio. Long-Term Outcomes Over an average post-treatment follow-up of 5.3 years, significant differences in long-term outcomes became evident between the two groups. Every patient in the persistent-C3 group experienced a relapse, while none in the resolved-C3 group relapsed (100% vs. 0% relapse rate; p = 0.006). In our cohort, all patients who cleared glomerular C3 deposits remained in remission during follow-up, whereas all patients with persistent glomerular C3 deposition eventually relapsed. Representative case examples are shown in Fig. 3 . In the patient whose glomerular C3 deposits resolved after treatment, a follow-up biopsy revealed restoration of the podocyte structure and an absence of electron-dense immune deposits. This patient remained in remission throughout the follow-up period. Conversely, in the patient with persistent C3 deposition, a follow-up biopsy indicated ongoing subepithelial deposits and new sclerosis (Fig. 3 I–K) despite an initial improvement in proteinuria. The patient subsequently experienced an early relapse. These findings suggest that residual glomerular C3 deposition after treatment could indicate ongoing subclinical disease activity and be associated with a higher risk of relapse. Discussion Our results indicate that continued glomerular C3 deposition following immunosuppressive therapy is linked to unfavorable long-term outcomes in patients with MN, whereas the absence of glomerular C3 is associated with prolonged remission and favorable histological changes. Importantly, persistent C3 deposition predicts a heightened risk of disease recurrence, even among patients who initially achieve clinical remission. These findings highlight the importance of monitoring the dynamics of C3 deposition in MN for prognostic assessment [ 5 ]. Ongoing activation of the complement system likely contributes to subclinical podocyte damage and glomerular injury, potentially explaining the elevated relapse rates observed in these patients. Previous studies have shown a link between persistent C3 deposition and negative outcomes in MN [ 6 , 7 ]. However, Troyanov et al. [ 8 ] observed that while C3 deposition correlates with disease severity, it is not an independent predictor of renal outcomes. Instead, they highlighted the prognostic importance of segmental sclerosis and tubular atrophy [ 5 ]. A significant limitation of their research was the absence of follow-up biopsy data to track changes in C3 over time. Our study fills this gap by examining alterations in C3 status pre- and post-treatment. This longitudinal analysis revealed that ongoing C3 deposition, rather than initial C3 deposition, significantly increased the risk of relapse. Therefore, monitoring histopathological changes through successive biopsies can offer valuable prognostic insights that complement clinical information. From a pathophysiological perspective, complement activation is central to podocyte injury in MN pathogenesis. Autoantibody-mediated complement activation results in C3 deposition, leading to the generation of C3a, which then binds to C3a receptors on podocytes. This interaction induces oxidative stress and apoptosis, compromising the glomerular filtration barrier and enhancing proteinuria [ 9 – 11 ]. Zhang et al. [ 9 ] demonstrated that inhibiting C3a–C3aR interactions can alleviate podocyte damage in MN models. Our study expands on this concept by indicating that the resolution of C3 deposition post-therapy could act as a prognostic indicator of positive outcomes. Collectively, these findings support the hypothesis that resolving complement activation is crucial for sustaining MN remission. Our study has several limitations. First, this is a retrospective analysis from a single center with a small sample size, which may limit the generalizability of our findings and preclude any causal inferences. Therefore, the relationships observed should be interpreted as associations rather than as evidence of causation. Second, follow-up kidney biopsies were performed based on clinical indications rather than a standardized schedule, introducing potential selection bias regarding which patients underwent repeat biopsies. Third, although the mean follow-up duration exceeded 5 years, it may still be insufficient to capture very late outcomes, such as progression to ESKD. These limitations highlight the need for cautious interpretation of our findings and support the necessity for prospective, multi-center studies with larger cohorts to validate the prognostic value of dynamic changes in glomerular C3 deposition. Conclusion The resolution of glomerular C3 deposits following immunosuppressive therapy has been associated with sustained remission and favorable histological changes in MN, whereas persistent C3 deposition was associated with ongoing disease activity and high relapse risk. These findings underscore the prognostic value of follow-up biopsies in monitoring C3 deposition dynamics in MN and highlight the potential role of complement activation in the disease course. No causal relationship can be established from this observational study, but our findings provide a rationale for further investigation. Declarations Ethics approval and consent to participate The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and approved by the Institutional Review Board of the Veterans Healthcare Service Medical Center, Seoul (IRB No. BOHUN 2025-02-023-001). Consent for publication Not applicable Competing interests The authors declare that they have no competing interests Funding This study received no specific grants from any funding agency. Author Contribution W-H.C.: Formal analysis, original draft preparation, and editing. H.S.L.: Pathological review. B.S.C.: Supervision and conceptualization. All authors have read and approved the submission of the manuscript. Acknowledgments Not applicable Availability of data and materials All data generated or analyzed during this study are included in this published article and its supplementary information files. Additional data are available from the corresponding author upon reasonable request, in accordance with institutional data-sharing policies, and to ensure patient confidentiality. References Polanco N, Gutiérrez E, Covarsí A, Ariza F, Carreño A, Vigil A, Baltar J, Fernández-Fresnedo G, Martín C, Pons S. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol. 2010;21:697–704. Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med. 2011;364:689–90. van de Logt A-E, Fresquet M, Wetzels JF, Brenchley P. The anti-PLA2R antibody in membranous nephropathy: what we know and what remains a decade after its discovery. Kidney int. 2019;96:1292–302. Li J, Chen B, Gao C, Huang J, Wang Y, Zhang S, Xu Y, Guo W, Wang R. Clinical and pathological features of idiopathic membranous nephropathy with focal segmental sclerosis. BMC nephrol. 2019;20:1–10. Chen Y, Tang L, Feng Z, Cao X, Sun X, Liu M, Liu S, Zhang X, Li P, Wei R. Pathological predictors of renal outcomes in nephrotic idiopathic membranous nephropathy with decreased renal function. J Nephrol. 2014;27:307–16. Ryu J, Baek E, Son H-E, Ryu J-Y, Jeong JC, Kim S, Na KY, Chae D-W, Kim SP, Kim SH. Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis. Kidney Res Clin Pract. 2023;42:98. Oto OA, Demir E, Mirioglu S, Dirim AB, Ozluk Y, Cebeci E, Basturk T, Ucar AR, Soltanova L, Nuriyev K. Clinical significance of glomerular C3 deposition in primary membranous nephropathy. J Nephrol. 2021;34:581–7. Troyanov S, Roasio L, Pandes M, Herzenberg A, Cattran D. Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney int. 2006;69:1641–8. Zhang Q, Bin S, Budge K, Petrosyan A, Villani V, Aguiari P, Vink C, Wetzels J, Soloyan H. La Manna G. C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy. JCI insight. 2024;9. Law SA, Dodds AW. The internal thioester and the covalent binding properties of the complement proteins C3 and C4. Protein Sci. 1997;6:263–74. Gao S, Cui Z, Zhao M-h. Complement C3a and C3a receptor activation mediates podocyte injuries in the mechanism of primary membranous nephropathy. J Am Soc Nephrol. 2022;33:1742–56. References. Polanco N, Gutiérrez E, Covarsí A, Ariza F, Carreño A, Vigil A, Baltar J, Fernández-Fresnedo G, Martín C, Pons S. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol. 2010;21(4):697–704. Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med. 2011;364(7):689–90. van de Logt A-E, Fresquet M, Wetzels JF, Brenchley P. The anti-PLA2R antibody in membranous nephropathy: what we know and what remains a decade after its discovery. Kidney Int. 2019;96(6):1292–302. Li J, Chen B, Gao C, Huang J, Wang Y, Zhang S, Xu Y, Guo W, Wang R. Clinical and pathological features of idiopathic membranous nephropathy with focal segmental sclerosis. BMC Nephrol. 2019;20:1–10. Chen Y, Tang L, Feng Z, Cao X, Sun X, Liu M, Liu S, Zhang X, Li P, Wei R. Pathological predictors of renal outcomes in nephrotic idiopathic membranous nephropathy with decreased renal function. J Nephrol. 2014;27:307–16. Ryu J, Baek E, Son H-E, Ryu J-Y, Jeong JC, Kim S, Na KY, Chae D-W, Kim SP, Kim SH. Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis. Kidney Res Clin Pract. 2023;42(1):98. Oto OA, Demir E, Mirioglu S, Dirim AB, Ozluk Y, Cebeci E, Basturk T, Ucar AR, Soltanova L, Nuriyev K. Clinical significance of glomerular C3 deposition in primary membranous nephropathy. J Nephrol. 2021;34:581–7. Troyanov S, Roasio L, Pandes M, Herzenberg A, Cattran D. Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int. 2006;69(9):1641–8. Zhang Q, Bin S, Budge K, Petrosyan A, Villani V, Aguiari P, Vink C, Wetzels J, Soloyan H. La Manna G: C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy. JCI insight 2024, 9(4). Law SA, Dodds AW. The internal thioester and the covalent binding properties of the complement proteins C3 and C4. Protein Sci. 1997;6(2):263–74. Gao S, Cui Z, Zhao M-h. Complement C3a and C3a receptor activation mediates podocyte injuries in the mechanism of primary membranous nephropathy. J Am Soc Nephrol. 2022;33(9):1742–56. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6434093","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":453414901,"identity":"42ea5a20-0108-4612-a9d8-a50c2be8f3ec","order_by":0,"name":"Won-Hee Cho","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYDACZgaGAwwMEnL8pGqxMJZsINGuisQNB4hVq9vOe/DQjQoJxs23m59JfNzDIM8vRkCz2WG+hMM5ZySYze4cM5Oc8YzBcObsBEJaeAwO57ZJsJndSDA25jnAkGBwmygt/yR4jGekfzb+Q7yWBgkJA4kcw8cMRGvJOQbUcSOn8GHPAQki/HL+jPHnnJq6+v4Z6RsO/DhgI88vTUALOpAgTfkoGAWjYBSMAuwAAAVoQ4f4SgMEAAAAAElFTkSuQmCC","orcid":"","institution":"Veterans Healthcare Service Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Won-Hee","middleName":"","lastName":"Cho","suffix":""},{"id":453414902,"identity":"87997e8f-cc66-4de0-ac4e-b3a3ed46de54","order_by":1,"name":"Byoung-Soo Cho","email":"","orcid":"","institution":"Dr.Cho’s Kidney Clinic","correspondingAuthor":false,"prefix":"","firstName":"Byoung-Soo","middleName":"","lastName":"Cho","suffix":""},{"id":453414903,"identity":"3a477c15-9bfa-489f-84bc-46824e57cf94","order_by":2,"name":"Hyun-Soon Lee","email":"","orcid":"","institution":"Hankook Renal Pathology Lab.","correspondingAuthor":false,"prefix":"","firstName":"Hyun-Soon","middleName":"","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2025-04-12 10:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6434093/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6434093/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82355782,"identity":"ac461e6a-6f6e-4840-a999-89ce07a7d818","added_by":"auto","created_at":"2025-05-09 11:15:42","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":41571,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of patient selection for study on glomerular C3 deposition in membranous nephropathy.\u003c/p\u003e","description":"","filename":"Figure1..jpg","url":"https://assets-eu.researchsquare.com/files/rs-6434093/v1/b0000e69508d1e2fef53b97c.jpg"},{"id":82355783,"identity":"52d2c86c-f61c-40f0-8958-3b6ab69ce185","added_by":"auto","created_at":"2025-05-09 11:15:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":164635,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological and clinical comparisons between groups with and without persistent glomerular C3 deposition in membranous nephropathy.\u003c/p\u003e","description":"","filename":"Figure2..png","url":"https://assets-eu.researchsquare.com/files/rs-6434093/v1/c36ba1d385d84edbc6f46843.png"},{"id":82358236,"identity":"8178bb78-5675-4789-8c8e-cd469b60ba30","added_by":"auto","created_at":"2025-05-09 11:23:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1964289,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative histopathological findings in two patients with membranous nephropathy before and after treatment. A 1-year-old male: Initial biopsy findings (A-C) and follow-up biopsy findings (D, E). (A) Light microscopy showing a moderately enlarged glomerulus with mild mesangial hypercellularity and an increased mesangial matrix (periodic acid-Schiff; original magnification, ×400). (B) Electron microscopy showing numerous diffuse subepithelial deposits (red arrows). (C) Immunofluorescence demonstrated C3 and IgG in diffuse granular peripheral staining (C and C3 deposits). (D) Light microscopy showing a slightly enlarged normocellular glomerulus (periodic acid-Schiff staining; original magnification, ×400). (E) Electron microscopy showing numerous diffuse intramembranous and subepithelial dissolved deposits with almost no electron-dense material. Epithelial foot processes exhibited focal effacement. A 51-year-old male: Initial biopsy findings (F–H) and follow-up biopsy findings (I–K). (F) Light microscopy showing a slightly enlarged glomerulus with mild-to-moderate mesangial hypercellularity (periodic acid-Schiff stain; original magnification, ×400). (G) Electron microscopy showing numerous diffuse subepithelial deposits (red arrows) and a few tiny subendothelial deposits. The glomerular basement membrane was diffusely thickened with irregular contours, and the epithelial cell foot processes exhibited marked focal effacement. (H) Immunofluorescence showing diffuse granular peripheral and/or mesangial staining of IgG, IgM, IgA, C3, and C1q. (H and C3 deposits). (I) Light microscopy showing moderately enlarged glomeruli with moderate mesangial hypercellularity and an increased mesangial matrix. Compared to the previous biopsy, de novo focal segmental glomerulosclerosis (FSGS) lesions were observed, affecting 27% of the glomeruli. (Periodic acid-Schiff; original magnification, ×400). (J) An electron microscopy image showing numerous diffuse subepithelial and intramembranous deposits (red arrows) with marked focal dissolution. The glomerular basement membrane was irregularly thickened, the capillary lumens were patent, and the epithelial cell foot processes exhibited marked focal effacement. (K) Immunofluorescence image showing diffuse granular peripheral staining for IgG, IgM, IgA, C3, and C1q (K and C3 deposits).\u003c/p\u003e","description":"","filename":"Figure3..png","url":"https://assets-eu.researchsquare.com/files/rs-6434093/v1/0bf96ddafa615983d512acc7.png"},{"id":83206208,"identity":"092ec159-5de9-475a-be99-cad903d1e601","added_by":"auto","created_at":"2025-05-21 07:24:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3693245,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6434093/v1/124aaf26-79ac-4f66-b292-663c23471fe4.pdf"},{"id":82355779,"identity":"174e5b41-56d8-470d-8080-fe9ac9a71dcd","added_by":"auto","created_at":"2025-05-09 11:15:42","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":20022,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6434093/v1/d0f482e32f09f3180a93da2f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic Significance of Dynamic Changes in Glomerular C3 Deposition in Membranous Nephropathy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMembranous nephropathy (MN) is a primary cause of nephrotic syndrome (NS) in adults and is characterized by subepithelial immune complex deposition along the glomerular capillary walls. MN is categorized into primary and secondary forms based on the origin of these immune complexes. Primary MN is associated with autoantigens such as the M-type phospholipase A\u003csub\u003e2\u003c/sub\u003e receptor (PLA2R), thrombospondin type 1 domain-containing 7A, and other antigens, while secondary MN results from autoimmune diseases (e.g., systemic lupus erythematosus), neoplasms, infections, and medications.\u003c/p\u003e \u003cp\u003eThe clinical course of primary MN is highly variable, ranging from spontaneous remission to frequent relapse and, in some cases, progression to end-stage kidney disease (ESKD) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Although anti-PLA2R antibody testing is a useful diagnostic and prognostic tool, approximately 20\u0026ndash;30% of patients with MN are seronegative for PLA2R, and antibody status alone does not consistently predict prognosis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Emerging evidence suggests that complement activation, particularly glomerular C3 deposition, plays a significant role in the pathophysiology and progression of MN [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the prognostic significance of C3 deposition\u0026mdash;particularly in follow-up biopsies\u0026mdash;remains unclear.\u003c/p\u003e \u003cp\u003eThis study assessed longitudinal changes in glomerular C3 deposition in patients with MN who showed reduced proteinuria following aggressive immunosuppressive treatment. We examined clinical outcomes in patients with and without persistent glomerular C3 deposition on subsequent biopsy to determine the prognostic significance of C3 deposition dynamics.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eStudy Population\u003c/p\u003e \u003cp\u003eThis retrospective study involved patients with histologically confirmed MN, including membranous lupus nephritis (Class V), who received intravenous (IV) methylprednisolone (MPD) pulse therapy and underwent follow-up kidney biopsies at Dr. Cho\u0026rsquo;s Kidney Clinic between September 1, 2013, and December 31, 2021. Out of 1,649 outpatient kidney biopsies conducted during this period, 31 (1.88%) were histologically diagnosed as MN. Eleven patients (0.67%) achieved complete or partial remission following IV MPD pulse therapy and underwent repeat biopsies. These 11 patients constituted the study cohort (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Initial biopsy indications included NS resistant to oral glucocorticoids (n\u0026thinsp;=\u0026thinsp;6), persistent non-nephrotic-range proteinuria despite oral glucocorticoid therapy (n\u0026thinsp;=\u0026thinsp;2), and combined proteinuria with hematuria (n\u0026thinsp;=\u0026thinsp;3). Two patients were eventually diagnosed with membranous lupus nephropathy (WHO Class V), while nine were found to have primary MN upon repeat biopsy analysis. For analysis, patients were categorized into two groups based on the presence or absence of glomerular C3 deposition in follow-up biopsies; eight patients showed no C3 deposition on repeat biopsy, whereas three exhibited persistent glomerular C3 deposition.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistopathological Evaluation\u003c/p\u003e \u003cp\u003eThe kidney biopsy specimens underwent processing and evaluation at the Korea Pathology Laboratory (Seoul, Korea). Each sample contained a minimum of eight glomeruli. For light microscopy, tissues were fixed in 10% formalin, embedded in paraffin, sectioned at 2\u0026ndash;4\u0026micro;m, and stained with hematoxylin-eosin and periodic acid\u0026ndash;Schiff. The degree of interstitial fibrosis and tubular atrophy (IFTA) was semi-quantitatively graded on a scale of 0\u0026ndash;3 as follows: 0 (normal), 1 (mild, \u0026lt; 25% of the interstitium), 2 (moderate, 25\u0026ndash;50%), and 3 (severe, \u0026gt; 50%). Immunofluorescence microscopy was conducted on frozen sections using fluorescein isothiocyanate-labeled antibodies against IgG, IgA, IgM, C3, C1q, C4, and fibrinogen. The staining intensity was graded from 0\u0026ndash;3: 0 (negative), 1 (weak), 2 (moderate), and 3 (strong).\u003c/p\u003e \u003cp\u003eTreatment Protocol\u003c/p\u003e \u003cp\u003eAll patients received IV MPD pulse therapy at 10\u0026ndash;20 mg/kg (maximum 1 g/day) for three consecutive days per cycle. The number of pulse cycles, typically 10\u0026ndash;15, was individualized based on pathological findings, laboratory results, and overall clinical status, with a minimum 2-week interval between cycles. Between MPD pulses, patients received oral prednisolone at approximately 0.5 mg/kg daily, which was gradually tapered and discontinued within three months of completing MPD pulse therapy. A follow-up biopsy was performed after completion of therapy to assess post-treatment histopathological changes.\u003c/p\u003e \u003cp\u003eData Collection and Statistical Analysis\u003c/p\u003e \u003cp\u003eClinical and laboratory data were gathered from medical records, including demographics (age and gender), comorbid conditions such as hypertension and diabetes mellitus, laboratory findings (serum protein, albumin, cholesterol, and renal function tests), and detailed histopathological characteristics of each biopsy. Key outcome measures included changes in renal function (serum creatinine level and eGFR), proteinuria, and disease recurrence during the follow-up period. Continuous variables were compared between groups using the Mann\u0026ndash;Whitney U test, while categorical variables were compared using Fisher\u0026rsquo;s exact test. Statistical analyses were conducted using SPSS Statistics version 22 (IBM Corp., Chicago, IL, USA) and GraphPad Prism 8.0 (GraphPad Software, San Diego, CA, USA). Statistical significance was defined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePatient Characteristics\u003c/p\u003e\n\u003cp\u003eAmong the 11 patients with pathological features of MN evaluated via repeat biopsy, eight exhibited resolution of glomerular C3 deposition, while three exhibited persistent deposition (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The baseline characteristics of the initial and follow-up biopsies are summarized in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age was higher in the no-C3 group. The distribution of sex and comorbidities (e.g., diabetes mellitus and hypertension) was similar between the groups. Both groups demonstrated stable estimated glomerular filtration rate (eGFR), and the urine protein-to-creatinine ratio (UPCR) significantly improved in all patients. After MPD therapy, NS resolved in six patients\u0026mdash;five in the no-C3 group and one in the persistent-C3 group.\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics of participants at initial and follow-up kidney biopsies.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 20.0157%;\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" style=\"width: 32.0826%;\"\u003e\n \u003cp\u003eFirst biopsy\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" style=\"width: 31.6038%;\"\u003e\n \u003cp\u003eRepeat biopsy\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003eNo C3 deposition (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003eC3 deposition (N\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003eNo C3 depositon (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003eC3 deposition (N\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e46.0 (33.5\u0026ndash;55.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e36.0 (21.5\u0026ndash;44.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.474\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e47.0 (34.5\u0026ndash;56.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e36.0 (21.5\u0026ndash;44.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.474\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eGender (male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e4 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e4 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eDM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e1 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e1 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eHTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e7 (87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e3 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e7 (87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e3 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eDyslipidemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e6 (75.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e3 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e6 (75.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e3 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eFatty liver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eGout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eSBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e128.0 (107.8\u0026ndash;132.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e117.0 (114.5\u0026ndash;120.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.609\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e123.5 (119.8\u0026ndash;126.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e118.0 (116.5\u0026ndash;119.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eDBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e77.5 (70.5\u0026ndash;78.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e70.0 (70.0\u0026ndash;71.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e77.5 (72.8\u0026ndash;80.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e70.0 (70.0\u0026ndash;75.0])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.759\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eBMI (kg/m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e25.9 (20.8\u0026ndash;29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e26.2 (21.7\u0026ndash;26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.776\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e26.2 (20.8\u0026ndash;29.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e26.2 (23.0\u0026ndash;26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.921\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e12.3 (10.8\u0026ndash;15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e13.0 (12.8\u0026ndash;13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.682\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e13.5 (11.4\u0026ndash;15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e13.9 (13.1\u0026ndash;14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eHct (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e39.0 (32.8\u0026ndash;42.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e39.0 (38.4\u0026ndash;41.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.918\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e42.4 (34.8\u0026ndash;43.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e38.0 (37.5\u0026ndash;41.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eWBC (/\u0026micro;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e7950.0 (6600.0\u0026ndash;9625.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e5000.0 (4250.0\u0026ndash;7000.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e8350.0 (7575.0\u0026ndash;9950.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e7400.0 (6500.0\u0026ndash;8500.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.497\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003ePLT (10\u0026sup3;/\u0026micro;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e313.0 (289.0\u0026ndash;340.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e196.0 (175.5\u0026ndash;259.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e315.0 (296.8\u0026ndash;353.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e237.0 (217.5\u0026ndash;268.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eProtein (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e5.4 (4.4\u0026ndash;6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e7.2 (5.8\u0026ndash;7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e6.5 (6.4\u0026ndash;6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e7.2 (6.7\u0026ndash;7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.682\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eAlbumin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e3.0 (2.5\u0026ndash;3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e3.4 (2.5\u0026ndash;4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e4.0 (4.0\u0026ndash;4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e4.4 (4.2\u0026ndash;4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.209\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eCholesterol (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e215.5 (186.0\u0026ndash;262.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e205.0 (187.5\u0026ndash;306.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e163.5 (155.0\u0026ndash;227.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e130.0 (128.5\u0026ndash;154.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.194\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eTriglyceride (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e161.0 (107.8\u0026ndash;256.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e166.0 (151.0\u0026ndash;180.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e154.0 (110.5\u0026ndash;166.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e127.0 (112.5\u0026ndash;145.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.607\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eHDL-Chol (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e75.9 (53.4\u0026ndash;89.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e39.8 (38.8\u0026ndash;49.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e70.7 (54.2\u0026ndash;89.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e64.4 (58.2\u0026ndash;71.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.776\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eLDL-Chol (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e103.5 (74.2\u0026ndash;147.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e134.0 (118.5\u0026ndash;221.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e75.5 (48.5\u0026ndash;124.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e52.6 (47.8\u0026ndash;59.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.497\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eBilirubin (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e0.6 (0.4\u0026ndash;0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e0.7 (0.4\u0026ndash;0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.758\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0.8 (0.5\u0026ndash;0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0.5 (0.4\u0026ndash;0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.682\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eALP (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e57.5 (44.5\u0026ndash;71.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e69.0 (65.0\u0026ndash;96.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e59.5 (37.0\u0026ndash;76.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e60.0 (54.0\u0026ndash;67.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.921\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eALT (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e23.0 (16.0\u0026ndash;27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e20.0 (16.0\u0026ndash;26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.608\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e21.0 (14.2\u0026ndash;32.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e15.0 (13.5\u0026ndash;26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.758\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eAST (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e25.0 (23.8\u0026ndash;27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e28.0 (24.0\u0026ndash;29.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.759\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e21.0 (18.8\u0026ndash;25.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e21.0 (18.5\u0026ndash;21.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.758\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eBUN (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e14.9 (14.5\u0026ndash;17.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e18.6 (18.1\u0026ndash;19.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e13.7 (12.1\u0026ndash;18.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e13.9 (13.4\u0026ndash;16.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e0.8 (0.7\u0026ndash;1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e0.7 (0.7\u0026ndash;0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.759\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0.8 (0.8\u0026ndash;0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0.8 (0.7\u0026ndash;0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.497\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eeGFR (MDRD, mL/min/1.73 m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e89.0 (73.5\u0026ndash;101.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e88.0 (87.5\u0026ndash;134.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e75.5 (73.8\u0026ndash;104.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e87.0 (86.0\u0026ndash;156.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eeGFR (CKD-EPI, mL/min/1.73 m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e88.5 (82.2\u0026ndash;90.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e96.0 (83.0\u0026ndash;101.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e81.0 (76.0\u0026ndash;91.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e92.0 (86.5\u0026ndash;98.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.354\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eFBS (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e94.5 (90.0\u0026ndash;104.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e107.0 (102.0\u0026ndash;112.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e93.0 (87.8\u0026ndash;100.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e92.0 (90.5\u0026ndash;94.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eUPCR (mg/g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e5.2 (3.1\u0026ndash;8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e1.7 (1.2\u0026ndash;8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.776\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0.1 (0.0\u0026ndash;0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0.1 (0.1\u0026ndash;0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.921\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eUrine_RBC(HPF)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.7907%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.7373%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.329\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.0246%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.0246%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e3 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e7 (87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003e1\u0026thinsp;~\u0026thinsp;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003e3\u0026thinsp;~\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e2 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003e6\u0026thinsp;~\u0026thinsp;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e2 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.0157%;\"\u003e\n \u003cp\u003eNephrotic syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.7907%;\"\u003e\n \u003cp\u003e6 (75.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 12.7373%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.0246%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5546%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 84.564%;\"\u003eAbbreviations: BMI, Body Mass Index; FBS, Fasting Blood Sugar; IFTA, interstitial fibrosis tubular atrophy; DBP, diastolic blood pressure; DM, diabetes mellitus; SBP, systolic blood pressure; UPCR, urine protein-to-creatinine ratio; PLT, platelet count; P values obtained from the chi-square test, Fisher\u0026rsquo;s exact test, or Mann\u0026ndash;Whitney U test\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eHistopathological and Therapeutic Findings\u003c/p\u003e\n\u003cp\u003eHistopathologic outcomes varied among the groups. In the resolved-C3 group, follow-up biopsies typically revealed restored podocyte foot processes and resolved subepithelial immune deposits (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eE). Conversely, the persistent-C3 group exhibited minimal histological improvement during follow-up. In some instances, there was evidence of ongoing or progressive disease activity despite clinical remission (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). In the persistent-C3 group, one patient exhibited essentially unchanged glomerular morphology between the initial and follow-up assessments (see Supplementary Table 1 for individual case details). Another patient progressed from lupus nephritis WHO Class IV at baseline to membranous lupus nephritis (WHO Class V) at follow-up (Supplementary Table 1). A third patient developed de novo focal segmental glomerulosclerosis lesions, affecting 27% of the glomeruli by the time of the follow-up biopsy (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). These findings suggest a more progressive disease course [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eHistopathological findings from initial and follow-up kidney biopsies.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 26.5286%;\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" style=\"width: 30.3042%;\"\u003e\n \u003cp\u003eFirst biopsy\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" style=\"width: 30.2049%;\"\u003e\n \u003cp\u003eRepeat biopsy\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003eNo C3 depositon (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003eC3 deposition (N\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003eNo C3 depositon (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003eC3 deposition (N\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBx glomerulus (No)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e23 (17\u0026ndash;26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e26 (22\u0026ndash;40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.539\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e22.5 (18.8\u0026ndash;26.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e41 (38.5\u0026ndash;41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSegmental Sclerosis (No)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0\u0026ndash;0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (0.5\u0026ndash;1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.402\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0\u0026ndash;1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e3 (1.5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003esegmental sclerosis (%)_Initial\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0\u0026ndash;1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e2 (1\u0026ndash;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.554\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0\u0026ndash;9.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e7 (3.5\u0026ndash;17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003e0.502\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eThe intensity of IFTA (N, %) (0,1:mild, 2:moderate)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5127%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003e0.903\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot observed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMild\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e4 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e5 (62.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e3 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e3 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFPE (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5127%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMild\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e7 (87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e3 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSevere\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e7 (87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIgA intensity (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5127%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003e0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot observed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e6 (75.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e7 (87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅠ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅡ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅢ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅣ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIgG intensity (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5127%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003e0.745\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot observed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅠ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅡ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅢ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e4 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅣ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e8 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e3 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIgM intensity (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5127%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot observed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e6 (75.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e5 (62.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅠ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e2 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅡ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅢ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅣ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eC3 (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5127%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot observed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e2 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e8 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅠ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅡ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e5 (62.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e3 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅢ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅣ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eC4 (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5127%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot observed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e8 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e8 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e3 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅠ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e2 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅡ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅢ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅣ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eC1q (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.5127%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.8685%;\"\u003e\n \u003cp\u003e0.134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.5705%;\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot observed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e7 (87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e8 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅠ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅡ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅢ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 26.5286%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eⅣ+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 13.5127%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 11.923%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.8685%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2146%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.4198%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.5705%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 87.7332%;\"\u003eAbbreviations: Bx, Biopsy; IFTA, interstitial fibrosis tubular atrophy; FPE, foot process effacement.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eDespite histology differences, both groups experienced clinical benefits from the therapy in terms of reducing proteinuria. IV MPD pulse therapy resulted in a significant decrease in proteinuria in both the resolved-C3 and persistent-C3 groups. The mean UPCR decreased from 5.2 g/g to 0.1 g/g in the resolved-C3 group and from 1.7 g/g to 0.7 g/g in the persistent-C3 group between the initial and follow-up assessments. This improvement was statistically significant within each group, and the post-treatment UPCR values did not show a significant difference between the two groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). No notable differences between the groups in residual segmental sclerosis or IFTA scores upon follow-up were observed (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Renal function remained stable, with serum creatinine levels and eGFR unchanged from baseline in both groups (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e), indicating the preservation of kidney function in all patients during the observation period.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical outcomes of participants based on the persistent or absence of C3 deposition in follow-up kidney biopsies.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo C3 deposition Median (IQR)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eC3 deposition Median (IQR)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-Value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiopsy interval (mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (10.0\u0026ndash;16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10 (9.0\u0026ndash;10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal follow-up duration (mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e72.5 (45.5\u0026ndash;122.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43 (41.5\u0026ndash;63.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.184\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSingle MPD dose (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e500 (500.0\u0026ndash;625.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e500 (437.5\u0026ndash;500.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.407\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal MPD cycles\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.5 (10.0\u0026ndash;15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10 (10.0\u0026ndash;12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.819\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eeGFR at Last follow-up (MDRD, mL/min/1.73 m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e100.5 (88.0\u0026ndash;112.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e96 (90.5\u0026ndash;110.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.921\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUPCR at Last follow-up (mg/g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.1 (0.1\u0026ndash;1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.7 (0.6\u0026ndash;1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.279\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRelapse rate (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eAbbreviations: eGFR, estimated glomerular filtration rate; MPD, methylprednisolone; UPCR, urine protein\u0026ndash;creatinine ratio.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eLong-Term Outcomes\u003c/p\u003e\n\u003cp\u003eOver an average post-treatment follow-up of 5.3 years, significant differences in long-term outcomes became evident between the two groups. Every patient in the persistent-C3 group experienced a relapse, while none in the resolved-C3 group relapsed (100% vs. 0% relapse rate; p\u0026thinsp;=\u0026thinsp;0.006). In our cohort, all patients who cleared glomerular C3 deposits remained in remission during follow-up, whereas all patients with persistent glomerular C3 deposition eventually relapsed. Representative case examples are shown in Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. In the patient whose glomerular C3 deposits resolved after treatment, a follow-up biopsy revealed restoration of the podocyte structure and an absence of electron-dense immune deposits. This patient remained in remission throughout the follow-up period. Conversely, in the patient with persistent C3 deposition, a follow-up biopsy indicated ongoing subepithelial deposits and new sclerosis (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eI\u0026ndash;K) despite an initial improvement in proteinuria. The patient subsequently experienced an early relapse. These findings suggest that residual glomerular C3 deposition after treatment could indicate ongoing subclinical disease activity and be associated with a higher risk of relapse.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur results indicate that continued glomerular C3 deposition following immunosuppressive therapy is linked to unfavorable long-term outcomes in patients with MN, whereas the absence of glomerular C3 is associated with prolonged remission and favorable histological changes. Importantly, persistent C3 deposition predicts a heightened risk of disease recurrence, even among patients who initially achieve clinical remission. These findings highlight the importance of monitoring the dynamics of C3 deposition in MN for prognostic assessment [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Ongoing activation of the complement system likely contributes to subclinical podocyte damage and glomerular injury, potentially explaining the elevated relapse rates observed in these patients.\u003c/p\u003e \u003cp\u003ePrevious studies have shown a link between persistent C3 deposition and negative outcomes in MN [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, Troyanov et al. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] observed that while C3 deposition correlates with disease severity, it is not an independent predictor of renal outcomes. Instead, they highlighted the prognostic importance of segmental sclerosis and tubular atrophy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. A significant limitation of their research was the absence of follow-up biopsy data to track changes in C3 over time. Our study fills this gap by examining alterations in C3 status pre- and post-treatment. This longitudinal analysis revealed that ongoing C3 deposition, rather than initial C3 deposition, significantly increased the risk of relapse. Therefore, monitoring histopathological changes through successive biopsies can offer valuable prognostic insights that complement clinical information.\u003c/p\u003e \u003cp\u003eFrom a pathophysiological perspective, complement activation is central to podocyte injury in MN pathogenesis. Autoantibody-mediated complement activation results in C3 deposition, leading to the generation of C3a, which then binds to C3a receptors on podocytes. This interaction induces oxidative stress and apoptosis, compromising the glomerular filtration barrier and enhancing proteinuria [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Zhang et al. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] demonstrated that inhibiting C3a\u0026ndash;C3aR interactions can alleviate podocyte damage in MN models. Our study expands on this concept by indicating that the resolution of C3 deposition post-therapy could act as a prognostic indicator of positive outcomes. Collectively, these findings support the hypothesis that resolving complement activation is crucial for sustaining MN remission.\u003c/p\u003e \u003cp\u003eOur study has several limitations. First, this is a retrospective analysis from a single center with a small sample size, which may limit the generalizability of our findings and preclude any causal inferences. Therefore, the relationships observed should be interpreted as associations rather than as evidence of causation. Second, follow-up kidney biopsies were performed based on clinical indications rather than a standardized schedule, introducing potential selection bias regarding which patients underwent repeat biopsies. Third, although the mean follow-up duration exceeded 5 years, it may still be insufficient to capture very late outcomes, such as progression to ESKD. These limitations highlight the need for cautious interpretation of our findings and support the necessity for prospective, multi-center studies with larger cohorts to validate the prognostic value of dynamic changes in glomerular C3 deposition.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe resolution of glomerular C3 deposits following immunosuppressive therapy has been associated with sustained remission and favorable histological changes in MN, whereas persistent C3 deposition was associated with ongoing disease activity and high relapse risk. These findings underscore the prognostic value of follow-up biopsies in monitoring C3 deposition dynamics in MN and highlight the potential role of complement activation in the disease course. No causal relationship can be established from this observational study, but our findings provide a rationale for further investigation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003e The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and approved by the Institutional Review Board of the Veterans Healthcare Service Medical Center, Seoul (IRB No. BOHUN 2025-02-023-001).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study received no specific grants from any funding agency.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eW-H.C.: Formal analysis, original draft preparation, and editing. H.S.L.: Pathological review. B.S.C.: Supervision and conceptualization. All authors have read and approved the submission of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eAll data generated or analyzed during this study are included in this published article and its supplementary information files. Additional data are available from the corresponding author upon reasonable request, in accordance with institutional data-sharing policies, and to ensure patient confidentiality.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePolanco N, Guti\u0026eacute;rrez E, Covars\u0026iacute; A, Ariza F, Carre\u0026ntilde;o A, Vigil A, Baltar J, Fern\u0026aacute;ndez-Fresnedo G, Mart\u0026iacute;n C, Pons S. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol. 2010;21:697\u0026ndash;704.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDebiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med. 2011;364:689\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan de Logt A-E, Fresquet M, Wetzels JF, Brenchley P. The anti-PLA2R antibody in membranous nephropathy: what we know and what remains a decade after its discovery. Kidney int. 2019;96:1292\u0026ndash;302.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi J, Chen B, Gao C, Huang J, Wang Y, Zhang S, Xu Y, Guo W, Wang R. Clinical and pathological features of idiopathic membranous nephropathy with focal segmental sclerosis. BMC nephrol. 2019;20:1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen Y, Tang L, Feng Z, Cao X, Sun X, Liu M, Liu S, Zhang X, Li P, Wei R. Pathological predictors of renal outcomes in nephrotic idiopathic membranous nephropathy with decreased renal function. J Nephrol. 2014;27:307\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyu J, Baek E, Son H-E, Ryu J-Y, Jeong JC, Kim S, Na KY, Chae D-W, Kim SP, Kim SH. Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis. Kidney Res Clin Pract. 2023;42:98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOto OA, Demir E, Mirioglu S, Dirim AB, Ozluk Y, Cebeci E, Basturk T, Ucar AR, Soltanova L, Nuriyev K. Clinical significance of glomerular C3 deposition in primary membranous nephropathy. J Nephrol. 2021;34:581\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTroyanov S, Roasio L, Pandes M, Herzenberg A, Cattran D. Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney int. 2006;69:1641\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Q, Bin S, Budge K, Petrosyan A, Villani V, Aguiari P, Vink C, Wetzels J, Soloyan H. La Manna G. C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy. JCI insight. 2024;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaw SA, Dodds AW. The internal thioester and the covalent binding properties of the complement proteins C3 and C4. Protein Sci. 1997;6:263\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao S, Cui Z, Zhao M-h. Complement C3a and C3a receptor activation mediates podocyte injuries in the mechanism of primary membranous nephropathy. J Am Soc Nephrol. 2022;33:1742\u0026ndash;56. References.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePolanco N, Guti\u0026eacute;rrez E, Covars\u0026iacute; A, Ariza F, Carre\u0026ntilde;o A, Vigil A, Baltar J, Fern\u0026aacute;ndez-Fresnedo G, Mart\u0026iacute;n C, Pons S. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol. 2010;21(4):697\u0026ndash;704.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDebiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med. 2011;364(7):689\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan de Logt A-E, Fresquet M, Wetzels JF, Brenchley P. The anti-PLA2R antibody in membranous nephropathy: what we know and what remains a decade after its discovery. Kidney Int. 2019;96(6):1292\u0026ndash;302.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi J, Chen B, Gao C, Huang J, Wang Y, Zhang S, Xu Y, Guo W, Wang R. Clinical and pathological features of idiopathic membranous nephropathy with focal segmental sclerosis. BMC Nephrol. 2019;20:1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen Y, Tang L, Feng Z, Cao X, Sun X, Liu M, Liu S, Zhang X, Li P, Wei R. Pathological predictors of renal outcomes in nephrotic idiopathic membranous nephropathy with decreased renal function. J Nephrol. 2014;27:307\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyu J, Baek E, Son H-E, Ryu J-Y, Jeong JC, Kim S, Na KY, Chae D-W, Kim SP, Kim SH. Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis. Kidney Res Clin Pract. 2023;42(1):98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOto OA, Demir E, Mirioglu S, Dirim AB, Ozluk Y, Cebeci E, Basturk T, Ucar AR, Soltanova L, Nuriyev K. Clinical significance of glomerular C3 deposition in primary membranous nephropathy. J Nephrol. 2021;34:581\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTroyanov S, Roasio L, Pandes M, Herzenberg A, Cattran D. Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int. 2006;69(9):1641\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Q, Bin S, Budge K, Petrosyan A, Villani V, Aguiari P, Vink C, Wetzels J, Soloyan H. La Manna G: C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy. JCI insight 2024, 9(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaw SA, Dodds AW. The internal thioester and the covalent binding properties of the complement proteins C3 and C4. Protein Sci. 1997;6(2):263\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao S, Cui Z, Zhao M-h. Complement C3a and C3a receptor activation mediates podocyte injuries in the mechanism of primary membranous nephropathy. J Am Soc Nephrol. 2022;33(9):1742\u0026ndash;56.\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":"membranous nephropathy, complement C3, glomerular deposition, prognosis, kidney biopsy, remission","lastPublishedDoi":"10.21203/rs.3.rs-6434093/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6434093/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eMembranous nephropathy (MN) is a primary cause of nephrotic syndrome in adults, with complement activation being a pivotal factor in its pathophysiology. Nevertheless, the prognostic significance of glomerular C3 deposition, particularly in subsequent biopsies, remains unclear. This study evaluates the influence of alterations in C3 deposition on the clinical prognosis of MN following intravenous methylprednisolone (MPD) treatment.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eThis retrospective study examined 11 patients with histologically confirmed MN who achieved remission following intravenous MPD pulse therapy and subsequently underwent a follow-up kidney biopsy. The patients were categorized according to the presence or absence of glomerular C3 deposition in the follow-up biopsy. Comparative analysis of clinical, laboratory, and histopathological data was conducted between the groups to evaluate treatment response and long-term outcomes.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eEight patients exhibited resolution of C3 deposition on follow-up biopsy, whereas three showed persistent C3 deposition. Despite both groups experiencing a notable decrease in proteinuria, persistent C3 deposition was associated with higher recurrence rates and limited histological improvement. Patients with resolved C3 deposition maintained remission over an average follow-up period of 5.3 years, whereas all patients with persistent C3 deposition experienced relapse during follow-up.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eThe intravenous MPD pulse therapy successfully induced remission of MN. Additionally, the disappearance of glomerular C3 deposition following therapy may serve as a prognostic indicator for long-term remission.\u003c/p\u003e","manuscriptTitle":"Prognostic Significance of Dynamic Changes in Glomerular C3 Deposition in Membranous Nephropathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 11:15:38","doi":"10.21203/rs.3.rs-6434093/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":"f3e5d971-8011-44fb-a037-7196ba8af1c7","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-21T07:23:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 11:15:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6434093","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6434093","identity":"rs-6434093","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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