The Significance of Foot Process Effacement in Renal Prognosis and Response to Treatment in IgA Nephropathy

The Significance of Foot Process Effacement in Renal Prognosis and Response to Treatment in IgA 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 The Significance of Foot Process Effacement in Renal Prognosis and Response to Treatment in IgA Nephropathy Kunyue Xu, Xue Jiang, Hong Liu, Anni Wang, Yuan Yuan, Jin Yu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8938552/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 Objectives This study aimed to analyze the impact of foot process effacement (FPE) severity on prognosis and treatment response in IgA nephropathy (IgAN). Methods In this retrospective study, 1,506 patients with biopsy-proven IgAN were categorized by FPE severity and followed for ≥12 months. The Kaplan-Meier survival and Cox regression analysis were performed to explore the relationship between FPE and adverse renal outcomes. The concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and the calibration curve were used to evaluate the nomogram model. Results A total of 1506 patients were included in this study and categorized into three groups according to the degree of FPE. Patients in the severe FPE group exhibited more severe clinical and pathological manifestations. Kaplan-Meier analysis revealed a significantly higher risk of renal failure in the severe FPE group compared to the others (log-rank P < 0.01). Multivariate Cox regression analysis further confirmed that FPE might be an independent risk factor for renal prognosis in IgAN (adjusted HR: 3.688, 95% CI: 1.548 - 8.784, P = 0.009). Subgroup analysis suggested that FPE level warranted particular attention in male patients aged ≤45 years. The FPE-incorporated nomogram showed excellent predictive performance for 3-, 5-, and 8-year end-stage renal disease (ESRD) risks(C-index=0.93; AUCs=0.958, 0.964, 0.892) and was well-calibrated. Furthermore, we found that FPE severity is an important factor influencing the treatment response, and immunosuppressive therapy (IST) can overcome this influence. For patients with severe FPE, IST is an essential intervention measure, and the recommended treatment duration is no less than 12 months. Conclusions FPE serves as an independent predictor of renal progression in patients with IgAN and holds significant clinical value. IgA nephropathy foot process effacement prognosis immunosuppressive therapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Introduction IgA nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis globally and constitutes a common cause of severe renal failure in young adults [1]. According to reports, the annual incidence of IgAN ranges from 0.2 to 5 cases per 100,000 individuals, with the highest prevalence observed in East Asian countries [2]. The potential pathogenesis of IgAN has been analyzed at the sub-molecular level, primarily involving aberrant synthesis and glycosylation of IgA1, leading to elevated levels of galactose-deficient IgA1 (gd-IgA1) in circulation. Multiple ethnic, genetic and environmental factors jointly contribute to and regulate renal injury [3-4]. As many as 30% to 40% of individuals with IgAN may progress to end-stage renal disease (ESRD) within 20 to 30 years following diagnosis [5]. Although research has found that histological features (such as MEST-C score), proteinuria and hypertension are risk factors for prognosis, increasing evidence indicates that foot process effacement (FPE) plays a crucial role in the progression of IgAN [6-7]. According to reports, FPE impacts renal survival in patients with kidney failure through both direct effects and indirect (mediated) effects via albuminuria [8]. Podocytes are highly specialized epithelial cells characterized by numerous interdigitating foot processes; together with the glomerular basement membrane (GBM) and endothelial cells, they maintain the glomerular filtration barrier [9]. One of the most typical morphological changes in the early stage of podocyte injury is FPE, which is characterized by swelling, retraction and bending of podocyte processes, thereby disrupting the typical interlacing pattern [10]. Studies have found that in glomerular diseases such as focal segmental glomerulosclerosis (FSGS) and lupus nephritis, the severity of FPE correlates with renal function decline and disease recurrence [11-12]. Nevertheless, the association between FPE levels and the clinical outcomes in IgAN remains unclear. To assess the impact of FPE on the renal prognosis and treatment response in patients with IgAN, we undertook this investigation. Material and methods Participants A total of 2,211 patients with biopsy-confirmed IgAN were enrolled from Hangzhou Hospital of Traditional Chinese Medicine between October 2014 and November 2023. Among them, 705 patients were excluded for the following reasons: 97 patients were under 18 years of age; 302 patients had a follow-up period of less than 12 months; 298 patients had secondary IgAN, chronic systemic diseases, active infections, or allergic diseases; and 8 patients lacked clinical or pathological data. The study was approved by the Ethics Committee of Hangzhou Hospital of Traditional Chinese Medicine and conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from all participants. (No. 2024KLL230). Clinical date Clinical data were retrospectively collected at the time of renal biopsy, including age, gender, body mass index (BMI), hemoglobin (Hb), albumin (ALB), total cholesterol (TCH), triglycerides (TG), low-density lipoprotein (LDL), high-sensitivity C-reactive protein (H-CRP), uric acid (UA), immunoglobulin G (IgG), immunoglobulin A (IgA), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), urine red blood cell (uRBC), 24-hour urinary total protein (24h UTP), and treatment plan. During the clinical follow-up period, the clinical data obtained from repeated examinations were regularly collected and continuously tracked until August 2025 or the occurrence of an endpoint event. eGFR was calculated using the adult CKD-EPI 2009 equation [13]. Histopathology All biopsy specimens were independently reviewed by two renal pathologists who were blinded to the clinical data. Renal biopsy specimens were processed for light microscopy using hematoxylin and eosin, periodic acid-Schiff, periodic acid-methenamine silver, and Masson’s trichrome staining, as well as immunofluorescence and electron microscopy. Renal histological lesions were assessed using the MEST-C score [14]. The mesangial hypercellularity of glomeruli was scored as M0 (≤50%) or M1 (>50%). Endocapillary hypercellularity was classified as E0 (absent) or E1 (present). Segmental glomerulosclerosis was recorded as S0 (absent) or S1 (present). Tubular atrophy and interstitial fibrosis were graded as T0 (≤25%), T1 (26–50%), or T2 (>50%). Crescentic lesions were categorized as C0 (absent), C1 (<25%), or C2 (≥25%). Podocyte FPE was defined as the loss or obliteration of the slit-like spaces between adjacent podocyte foot processes. The extent of FPE was assessed using the mean foot process width, as determined by the method of Gundersen, Seefeldt, and Osterby [15]. Each patient was observed under a visualized electron microscope for approximately 1-2 complete glomeruli, and each complete glomerulus contains approximately 5-8 capillary loops. The severity of FPE was assessed through a semi-quantitative visual inspection. The evaluation criteria were the proportion of FPE in the capillary loops of the glomerulus, and it was classified into five groups based on the severity of FPE: <25%, 25%–49%, 50%–74%, 75%–89%, and ≥90%. In this study, we ultimately divided the enrolled IgAN patients into three groups based on the percentage of FPE in the capillary loops: mild (<50%), moderate (50%–74%), and severe (≥75%). Endpoint event The primary renal endpoint event was defined as either a 50% decline in eGFR or ESRD, which was characterized by an eGFR <15 mL/min/1.73m² or the initiation of kidney replacement therapy, including hemodialysis, peritoneal dialysis, or kidney transplantation. Therapeutic response Among the 1506 enrolled patients, individuals with complete follow-up data (including 24h UTP and Scr) at 3, 6, and 12 months after treatment initiation were selected for the evaluation of therapeutic efficacy (Figure 1). Immunosuppressive therapy (IST) was defined as treatment with steroids or immunosuppressants, irrespective of treatment duration or dosage. Complete clinical remission (CR) was defined as patients with 24h UTP ≤ 0.3 g/d and stable renal function (eGFR reduction ≤ 30%). Partial remission (PR) was defined as a >50% reduction in proteinuria from baseline, accompanied by 24h UTP < 1g/24h and stable renal function, without meeting the CR criteria. Non-response (NR) refers to cases that do not meet the CR or PR criteria. Statistical Analyses All statistical analyses were conducted using IBM SPSS software (version 27.0) and R statistical software (version 4.5.1). The Python programming language (version 3.9) was used to plot the graphs. Continuous distributions were presented as the mean ± standard deviation and were analyzed using an unpaired t test or one-way ANOVA, whereas skewed distributions were displayed as the median with interquartile range and were analyzed using the Kruskal-Wallis H test or the nonparametric Mann-Whitney U test. Categorical variables were presented as frequencies, and comparisons were performed using the χ² test or Fisher’s exact tests. Spearman correlation analysis was conducted to examine the relationship between FPE and clinicopathological variables. The Kaplan-Meier survival curve and Log-rank test were applied to compare renal survival across different levels of FPE. Cox regression models were employed to conduct subgroup analyses. Cox regression was performed to identify independent prognostic factors associated with IgAN outcomes. A nomogram prediction model was constructed through a stepwise approach to identify optimal combinations of predictors for estimating the prognosis of IgAN. The predictive accuracy of the nomograms was assessed using the concordance index (C-index) and receiver operating characteristic (ROC) curve analysis, and the discriminative ability was validated through calibration plots. P < 0.05 was considered significant. Results Baseline characteristics This retrospective analysis included 2,211 individuals diagnosed with IgAN through kidney biopsy at Hangzhou Hospital of Traditional Chinese Medicine from October 2014 to November 2023. Based on the predefined criteria for inclusion and exclusion in the study, a total of 1,506 patients were included in the final analysis (as shown in Fig. 1). The study cohort comprised 603 (40%) males and 903 (60%) females, with a median age of 44 (36, 54) years. Patients were categorized into three groups according to the degree of FPE. The largest proportion was classified as the mild group (1,026 patients, 68.1%), followed by the moderate group (316 patients, 21.0%), while the severe group included only 164 patients (10.9%). The baseline data analysis revealed that, except for Hb, there were statistically significant differences in all other clinical indicators among the groups. The severe group had the highest age and the largest proportion of male patients. Compared with the other two groups, the BMI, TCH, TG, LDL, H-CRP, UA, Scr, and 24h UTP of the severe group patients were higher, while ALB and eGFR were lower, and the differences were statistically significant. The MESTC score of renal pathology showed that in the severe group, the E lesions, T lesions and C lesions were more severe (P < 0.05). Patients with higher foot process effacement levels were more likely to receive IST and exhibited an increased risk of endpoint event, as shown in Table 1. Correlation of FPE with clinical and pathological characteristics The Spearman correlation analysis was performed to evaluate the associations between variables, and the results revealed that FPE was significantly positively correlated with age (r = 0.107, P < 0.001), BMI (r = 0.108, P < 0.001), TCH (r = 0.208, P < 0.001), TG (r = 0.217, P < 0.001), LDL (r = 0.212, P < 0.001), UA (r = 0.169, P < 0.001) and 24h UTP (r = 0.456, P < 0.001), while it was significantly negatively correlated with gender (r = -0.078, P = 0.002), ALB (r = -0.309, P < 0.001), IgG (r = -0.209, P < 0.001), and eGFR (r = -0.297, P < 0.001). Furthermore, with respect to the Oxford classification of renal pathology, FPE was positively correlated with the Oxford classifications E, S, T, and C (r = 0.070, P = 0.009;r = 0.081, P = 0.002;r = 0.236, P < 0.001;r = 0.120, P < 0.001). (Figure 2) Associations of FPE with risk of renal survival rate During the median follow-up of 44.80 (26.98, 68.83) months, a total of 103 patients reached the endpoint event, accounting for 6.8%. Moreover, there were significant differences in the event occurrence rates among patients with different degrees of FPE: mild (4.0%), moderate (9.4%), and severe (18.9%)(as shown in Table 1). The Kaplan-Meier analysis indicated that increased severity of foot process effacement was significantly associated with an increased risk of renal failure (log-rank test, P < 0.01; shown in Fig. 3). The mean kidney survival time of patients in the severe group (81.78 months, 95% CI: 75.17 - 88.38) was significantly shorter than that in the mild group (103.87 months, 95% CI: 102.14-105.60) and the moderate group (97.13 months, 95% CI : 93.80 - 100.47). In unadjusted Cox analysis, the hazard of poor renal prognosis in the mild group was lower than that in the moderate group (HR: 2.053, 95% CI: 1.284 - 3.285) and severe group (HR: 5.043, 95% CI: 3.162 - 8.043)(P < 0.001). To minimize the impact of other related factors, we constructed three models incorporating relevant clinical, pathological, and treatment variables. As depicted in Models 1,2 and 3, the multivariate Cox regression analysis manifested that the high level of foot process effacement was an independent risk factor for renal progression even after adjustment for clinical parameters (gender, Hb, Alb, TG, LDL, UA, 24h UTP and eGFR) (adjusted HR: 2.451, 95% CI: 1.425 - 4.217, P = 0.002) and combined with pathologic lesions (Oxford MEST-C) (adjusted HR: 3.551, 95% CI:1.477-8.538, P = 0.009) and combined with treatment (adjusted HR: 3.688, 95% CI: 1.548-8.784, P = 0.009), as shown in Table 2. Subgroup analysis According to gender (male / female), age (≤ 45 / > 45), BMI (≤ 26 / > 26), ALB (≤ 38 / > 38), UA (≤ 360 / > 360), TCH (≤ 4.5 / > 4.5), LDL (≤ 2.8 / > 2.8), and steroid/immunosuppressants (NO / Yes), we performed a series of subgroup analyses to evaluate potential heterogeneity among different groups. The results showed that for male patients aged ≤ 45 years, severe FPE was an independent risk factor for adverse renal outcomes (HR: 6.943, 95% CI: 2.076 - 23.221, P = 0.002; HR: 5.717, 95% CI: 1.295 - 25.239, P = 0.021). Interestingly, in female patients aged > 45 years, this risk was significantly reduced (HR: 0.660, 95% CI: 0.091 - 4.774, P = 0.681; HR: 2.730, 95% CI: 0.579 - 12.877, P = 0.204) as shown in Fig. 4. This suggests that for male patients aged 45 or younger, we should pay more attention to the level of FPE. Establish and validate the nomogram prognostic model Through Cox regression analysis, we selected gender, 24h UTP, eGFR, FPE, Oxford classification scores S and T to construct a nomogram prediction model for evaluating the prognosis of IgAN (Figure 5). The C-index of the nomogram model was 0.93, and the areas under the receiver operating characteristic curve (AUC) at 3, 5, and 8 years were 0.958, 0.964, and 0.892 respectively (Figure 6), demonstrating its high accuracy in predicting adverse outcomes in patients with IgAN. In addition, we also evaluated the calibration of the nomogram model using calibration curves (Figure 7). The graphs revealed good agreement between predicted and observed outcomes, further validating the reliability of the nomogram model in predicting the prognosis of patients with IgAN. Multivariate ROC Curve Associated with FPE and the IIgAN-PRT Model Multivariable logistic regression analyses were conducted by incorporating the relevant parameters from the original IIgAN-PRT models, both with and without FPE. The ROC curve demonstrated a higher AUC for the model with FPE (AUC: 0.977) compared to the model without FPE (AUC: 0.976), as shown in Fig. 8. Impact of FPE levels on the response to treatment To further clarify the influence of FPE severity on the response to treatment, 288 patients were selected for analysis as per the requirements. The results showed that in patients not receiving IST, the cumulative remission rates (CR+PR) showed an increasing trend across the mild, moderate, and severe FPE groups over the treatment period. However, at the 12-month mark, the remission rate in the severe FPE group remained significantly lower than those in the mild and moderate groups (P=0.023). In contrast, among patients treated with IST, the three FPE severity groups also exhibited a general trend toward higher remission rates over time. A key finding was that at 12 months, the severe FPE group demonstrated a marked improvement in the cumulative remission rate, which was comparable to the rates observed in the mild and moderate groups, with no statistically significant difference (P=0.608) (Table 3, Figure 9). These results indicate that in the absence of IST, FPE severity was an important factor influencing treatment response, with more severe FPE associated with worse the treatment outcomes. For patients who received IST, it can improve the treatment response of patients with severe FPE over a long period (12 months) and reduce the differences in treatment responses among patients with different degrees of FPE severity. Discussion IgAN represents the most common form of primary chronic glomerulopathy globally. The immune complexes composed of Gd-IgA1 and its specific autoantibodies deposit in the mesangial area, playing a key role in the pathogenesis of IgAN [16]. The deposition of immune complexes in the mesangial region induces mesangial cell proliferation, which subsequently exerts pathological effects on other renal cells, including podocytes and tubular epithelial cells [17]. Podocyte injury can further lead to podocyte detachment, podocyte hypertrophy, and foot process effacement [10]. Previous studies indicates that podocytopathy caused by podocyte loss can lead to segmental sclerosis, which is associated with the severity of IgAN [18, 19]. In a retrospective study involving 976 patients with IgAN, Guo Y et al. reported that participants with severe FPE were more likely to have higher 24hUPE, MESTC scores, and lower serum albumin, eGFR [20]. In our study, we also confirmed that patients with severe FPE had more clinical and pathological manifestations, and more patients receive immunosuppressive therapy. The incidence of endpoint events was significantly higher in the severe FPE group compared to the other two groups. K-M survival analysis demonstrated a statistically significant difference in the mean renal survival time among the three groups, with the severe FPE group showing a notably shorter renal survival time compared to the other two groups. Multivariate Cox regression analysis further suggested that FPE may serve as an independent risk factor for renal prognosis in IgAN, which is consistent with the research results of Gao L et al. [21]. Podocytes are terminally differentiated epithelial cells. A typical feature of FPE is the rearrangement of the podocyte cytoskeleton, which leads to the retraction and flattening of foot processes [22]. FPE is not merely a passive marker of injury but an active participant in the pathogenesis of IgAN. This structural derangement of FPE disrupts the integrity of the slit diaphragm, the crucial size-selective filtration barrier. Consequently, the glomerular permeability to proteins increases, manifesting clinically as proteinuria, a well-established driver of tubulointerstitial injury and fibrosis, and also the core mechanism by which FPE leads to the progression of IgAN [23, 24]. Furthermore, sustained injury triggers podocyte phenotypic changes, apoptosis, and eventual detachment, leading to irreversible glomerulosclerosis [25]. The degree of FPE observed on electron microscopy thus serves as a direct histomorphometric correlate of podocyte stress and loss. The research by Lee JH et al. indicated that proteinuria was a significant risk factor for the progression of IgAN and was positively correlated with the severity of foot process effacement [26]. A single-center retrospective study involving 107 patients with IgAN revealed that, beyond the established MEST-C score, ultrastructural lesions, specifically podocyte lesions, were associated with a lower renal survival rate, underscoring the prognostic value of lesions detected by transmission electron microscopy [27]. These findings confirm our conclusion, indicating that FPE is not just a secondary phenomenon but also a critical driver of glomerular injury, independently influencing the clinical course of IgAN. To explore whether the effect of FPE varies among different clinicopathological characteristics, we conducted a subgroup analysis. The results showed that FPE confers a higher risk in male patients aged ≤ 45 years. In addition, we incorporated gender, 24h UTP, eGFR, FPE, Oxford classification scores S and T into the assessment parameters for the first time and proposed a nomogram model. The model revealed that more severe FPE was associated with higher scores and an increased risk of endpoint events in IgAN patients at 3, 5, and 8 years. The C-index, AUC, and calibration plots further validated the reliability of the nomogram model. By comparing the predictive performance of the IIgANPRT model with and without FPE, we found that the inclusion of FPE improved the model's assessment capability. These findings suggest that FPE may serve as a predictor of renal function progression in IgAN. Glucocorticoids and other immunosuppressants are known to exert potent anti-inflammatory and immunomodulatory effects and are the main therapeutic strategies for podocytopathy. These drugs directly act on podocytes by regulating some cytokines and multiple signaling pathways related to cytoskeletal stability, cell maturation and survival [28, 29]. Specifically, glucocorticoids such as dexamethasone have been shown to stabilize the podocyte actin cytoskeleton by modulating the activity of small GTPases like RhoA, which are critical for maintaining the structural integrity of foot processes [30]. Furthermore, mycophenolate mofetil can inhibit the early abnormal hypertrophy and apoptosis of podocytes by modulating the expression of cell cycle related proteins p27 kip1 , p21 cip1 , and apoptosis related genes (such as bax, bcl-2 and cleaved caspase-3) [31]. Beyond its established role as a structural correlate of prognosis, our findings shed new light on the influence of FPE on therapeutic responsiveness in IgAN, particularly to immunosuppressive therapy. We demonstrated that in patients not receiving IST, the severity of FPE was a dominant factor determining therapeutic outcome, with more extensive effacement predicting a poorer response. This underscores the limitation of conservative treatment alone when confronted with severe podocyte injury. however, our data revealed that IST can reverse this trend. For patients receiving IST, we observed that the treatment could continuously improve the clinical response of patients with severe podocyte effacement at 12 months. Importantly, immunosuppressive therapy effectively diminished the previously observed disparities in treatment responses between patients with varying severities of FPE. This finding is supported by prior studies, where Wang Y et al. found that corticosteroids were more effective in reducing proteinuria and improving renal function in IgAN patients with active inflammatory lesions—pathological changes frequently accompanied by podocyte injury[32]. Several limitations of this study should be acknowledged. Firstly, its retrospective and single-center design may have introduced selection bias and limited the generalizability of the study results. Secondly, the assessment of FPE, though performed by experienced pathologists, remains semi-quantitative and subjective; the lack of a universally standardized, quantitative method for evaluating the degree of FPE is a notable constraint. Lastly, the follow-up duration, while substantial, may still be insufficient to capture the very long-term renal outcomes in a chronic disease like IgAN. Conclusion In conclusion, FPE, as a histopathological marker, may be an independent predictor of the progression to ESRD in IgAN patients, especially when the patients are male and aged ≤ 45 years. The constructed nomogram model incorporating FPE alongside key clinical parameters provides a practical tool for individualized risk stratification. Importantly, our findings offer novel insights into treatment, suggesting that IST can effectively overcome the adverse impact of severe FPE on treatment response. This indicates that for such patients, IST is a necessary intervention, and its course should be maintained for at least 12 months. Therefore, assessment of FPE should be integrated into the routine pathological evaluation of IgAN to guide both prognostic counseling and therapeutic decision-making. Abbreviations FPE foot process effacement IgAN IgA nephropathy C-index concordance index ROC Receiver Operating Characteristic AUC area under the receiver operating characteristic curve ESRD end-stage renal disease IST immunosuppressive therapy gd-IgA1 galactose-deficient IgA1 GBM glomerular basement membrane FSGS focal segmental glomerulosclerosis BMI body mass index Hb hemoglobin ALB albumin TCH total cholesterol TG triglycerides LDL low-density lipoprotein H-CRP high-sensitivity C-reactive protein UA uric acid IgG immunoglobulin G IgA immunoglobulin A Scr serum creatinine eGFR estimated glomerular filtration rate uRBC urine red blood cell 24h UTP 24-hour urinary total protein CR complete clinical remission PR partial remission NR non-response Declarations Acknowledgements We thank all clinicians at the Department of Nephrology, Hangzhou TCM Hospital Afliated to Zhejiang Chinese Medical University for their efforts in this study. Author Contributions KX: Writing - original draft, Methodology, Investigation, Ethics approval acquisition. XJ: Writing - original draft, Methodology, Software. HL and AW: patient follow-up. YY and JY: Writing - original draft. YD and SZ: Data curation. DY: Funding acquisition, Writing - review & editing. Funding Hangzhou Medical and Health Science and Technology Project under Grant No.ZD20240017; Medical Scientific Research Foundation of Zhejiang Province under Grant No.2025KY154; Medical Scientific Research Foundation of Zhejiang Province under Grant No.2025KY1146; The Construction fund of Key medical Disciplines of Hangzhou under Grand No.2025HZGF12, 2025HZPY05. Data availability The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Ethics approval and consent to participate All procedures carried out in studies involving human participants comply with the ethical standards of the Ethics Committee of Hangzhou TCM Hospital affiliated to Zhejiang Chinese Medical University, and follow the Helsinki Declaration and its later amendments or comparable ethical standards (No. 2024KLL230). Clinical trial number Not applicable. Consent for publication All authors read and approved the final manuscript. Competing interests The authors declare no competing interests. References Stamellou E, Seikrit C, Tang SCW, et al. IgA nephropathy. Nat Rev Dis Primers. 2023;9:67. https://doi.org/10.1038/s41572-023-00476-9. Pattrapornpisut P, Avila-Casado C, Reich HN. IgA Nephropathy: Core Curriculum. 2021. Am J Kidney Dis 2021;78:429-441. https://doi.org/10.1053/j.ajkd.2021.01.024. Gutiérrez E, Carvaca-Fontán F, Luzardo L, et al. A Personalized Update on IgA Nephropathy: A New Vision and New Future Challenges. 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Prognostic role of glomerular electron microscopy lesions in IgA nephropathy: "the devil is in the details". J Nephrol. 2023;36:2233-2243. https://doi.org/10.1007/s40620-023-01744-3. Kopp JB, Anders HJ, Susztak K, et al. Podocytopathies. Nat Rev Dis Primers. 2020;6:68. https://doi.org/10.1038/s41572-020-0196-7. Schönenberger E, Ehrich JH, Haller H, et al. The podocyte as a direct target of immunosuppressive agents. Nephrol Dial Transplant. 2011;26:18-24. https://doi.org/10.1093/ndt/gfq617 Welsh GI, Saleem MA. The podocyte cytoskeleton--key to a functioning glomerulus in health and disease. Nat Rev Nephrol. 2011;8:14-21. https://doi.org/10.1038/nrneph.2011.151. Lv W, Lou J, Zhang Y, et al. Mycophenolate mofetil inhibits hypertrophy and apoptosis of podocyte in vivo and in vitro. Int J Clin Exp Med. 2015;8:19781-19790. Wang Y, Huang N, Wang Y, et al. Comparative analysis between the safety and efficacy of oral corticosteroids versus corticosteroids pulse therapies in IgA nephropathy. Ren Fail. 2023;45:2255683. https://doi.org/10.1080/0886022X.2023.2255683. Tables Table 1 Characteristics of different degree of FPE in the study population. Variables Total(n=1506) Foot process effacement level Mild(n=1026) <50% Moderate(n=316) 50-74% Severe(n=164) ≥75% P value Age, years 44(36,54) 43(36,53) 44(36,54) 48(37.75,60.25) <0.001 Male, n（%） 603(40) 386(37.6) 135(42.7) 82(50) 0.006 BMI, kg/m2 23.05(20.93,25.37) 22.67(20.81,25.11) 23.34(20.87,25.39) 24.22(22.11,26.77) <0.001 Hb,g/L 125.67±18.37 126.20±17.78 125.07±19.01 123.48±20.53 0.171 ALB, g/L 38.30(35.50,40.70) 38.90(36.30,41.20) 37.60(34.30,39.80) 34.60(28.85,38.43) <0.001 TCH, mmol/L 4.67(4.06,5.37) 4.58(4.01,5.22) 4.75(4.06,5.40) 5.34(4.35,6.35) <0.001 TG, mmol/L 1.33(0.92,1.89) 1.21(0.85,1.76) 1.36(0.97,1.88) 1.77(1.39,2.41) <0.001 LDL, mmol/L 2.91(2.39,3.43) 2.85(2.33,3.33) 2.91(2.39,3.51) 3.38(2.71,4.09) <0.001 H-CRP, mg/L 1.00(0.48,2.64) 0.96(0.47,2.57) 1.07(0.50,2.57) 1.32(0.52,3.26) 0.029 UA, μmol/L 355(291.5,428.5) 343.5(282,421) 371(294,445) 399.5(344,474.5) <0.001 Scr, μmol/L 79(61,109) 75(58,98) 85(64,117) 108(78,156) <0.001 24h UTP, g/d 0.95(0.49,1.85) 0.69(0.38,1.24) 1.52(0.85,2.40) 2.51(1.53,4.60) <0.001 eGFR,（ml/min)/1.73m2 85.30(60.75,108.20) 91.30(69.55,111.70) 77.20(53.20,104.60) 53.90(39.00,77.35) <0.001 Oxford classification M0/M1(% of M1) 5/1501(99.7) 4/1022(92.7) 0/316(100) 1/163(99.4) 0.463 E0/E1(% of E1) 1006/500(33.2) 717/309(30.1) 198/118(37.3) 91/73(44.5) <0.001 S0/S1(% of S1) 373/1133(75.2) 253/773(75.3) 81/235(74.4) 39/125(76.5) 0.896 T0/T1/T2(% of [T1+T2]) 1059/359/88(29.7) 797/204/25(22.3) 195/92/29(38.3) 67/63/34(59.1) <0.001 C0/C1/C2(% of [C1+C2]) 930/448/128(38.3) 644/314/68(37.2) 190/86/40(39.9) 96/48/20(41.5) 0.005 Therapy,n(%) None steroid 1052(69.8) 754(73.4) 203(64.2) 95(57.9) <0.001 Steroid alone 321(21.3) 209(20.4) 74(23.4) 38(23.1) Steroid+immunosuppressants 133(8.8) 63(6.1) 39(12.3) 31(18.9) Endpoint event, n(%) happen 103(6.8) 42(4.0) 30(9.4) 31(18.9) <0.001 Table 2 Multivariate Cox regression analysis FPE and renal outcomes. Univariate Model 1 Model 2 Model 3 HR(95%CI) Mild (≤50%) 1.000(reference) 1.000(reference) 1.000(reference) 1.000(reference) Moderate(51-75%) 2.053(1.284-3.285) 1.019(0.619-1.679) 1.075(0.428-2.703) 1.246(0.490-3.172) Severe(＞75%) 5.043(3.162-8.043) 2.451(1.425-4.217) 3.551(1.477-8.538) 3.688(1.548-8.784) p for trend <0.001 0.002 0.009 0.009 Notes. Model 1:was adjusted for age, gender+clinic factors (Hb, Alb, TG, LDL, UA, 24h UTP and eGFR). Model 2:was adjusted for Model 1+Oxford classification(MEST-C). Model 3:was adjusted for Model 2+therapy. ALB, 24h UTP, and eGFR were transformed into binary variables with cutoff of 25, 1, and 45 respectively. Tubulointerstitial atrophy/interstitial fibrosis(T)was transformed into a binary variable of T0 and T1+T2. Crescent(C) was transformed into a binary variable of C0 and C1+C2. Abbreviations: CI, confidence intervals; HR, hazard ratios Table 3 Remission rates at 3, 6, 12 months after treatment. Without IST IST Variables Mild(N=104) Moderate(N=46) Severe(N=17) P-value Mild(N=60) Moderate(N=35) Severe(N=26) P-value 3 months, n(%) 0.008 0.109 CR 45(43.3) 8(17.4) 2(11.8) 23(38.3) 9(25.7) 3(11.5) PR 22(21.2) 13(28.3) 6(35.3) 12(20.0) 10(28.6) 6(23.1) NR 37(35.6) 25(54.3) 9(52.9) 25(41.7) 16(45.7) 17(65.4) 6 months, n(%) 0.102 0.027 CR 49(47.1) 14(30.4) 5(29.4) 26(43.3) 11(31.4) 2(7.7) PR 28(26.9) 15(32.6) 3(17.6) 14(23.3) 11(31.4) 9(34.6) NR 27(26.0) 17(37.0) 9(52.9) 20(33.3) 13(37.1) 15(57.7) 12 months, n(%) 0.023 0.608 CR 64(61.5) 21(45.7) 5(29.4) 32(53.3) 15(42.9) 13(50) PR 18(17.3) 17(37.0) 6(35.3) 11(18.3) 9(25.7) 8(30.8) NR 22(21.2) 8(17.4) 6(35.3) 17(28.3) 11(31.4) 5(19.2) Additional Declarations No competing interests reported. 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to Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xue","middleName":"","lastName":"Jiang","suffix":""},{"id":601909579,"identity":"1ae8e977-c5f5-4a61-b65d-24380f3eb44a","order_by":2,"name":"Hong Liu","email":"","orcid":"","institution":"Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hong","middleName":"","lastName":"Liu","suffix":""},{"id":601909580,"identity":"e4713619-8b59-4571-bcdb-67a8254a3708","order_by":3,"name":"Anni Wang","email":"","orcid":"","institution":"Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Anni","middleName":"","lastName":"Wang","suffix":""},{"id":601909582,"identity":"712ff18d-f34f-4bd4-9305-fe004cc3eb3f","order_by":4,"name":"Yuan Yuan","email":"","orcid":"","institution":"Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical 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10:39:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8938552/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8938552/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104405796,"identity":"cf55b964-ca29-4404-a084-90472c560558","added_by":"auto","created_at":"2026-03-11 12:23:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":912284,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart showing the number of IgAN patients included in the analyses.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8938552/v1/76212447bda33141f44e3f43.png"},{"id":104338132,"identity":"1458535a-3bfe-44df-84d7-cde9a6dad23f","added_by":"auto","created_at":"2026-03-10 16:18:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1664202,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between FPE with clinical and oxford classification.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8938552/v1/226e20edb9a5b3c9cd54ad8a.png"},{"id":104338134,"identity":"56565e16-1d62-401d-af21-5649e91aea8a","added_by":"auto","created_at":"2026-03-10 16:18:15","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1141864,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves of renal outcomes in different FPE level.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8938552/v1/72b38f4b22180b11f37c6a0c.png"},{"id":104338140,"identity":"9f43f7cc-13d0-4c94-964d-4d35c089dcf0","added_by":"auto","created_at":"2026-03-10 16:18:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1245409,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of subgroup and interaction effects analyses.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8938552/v1/7ebb4a42c657ca76373ff717.png"},{"id":104406142,"identity":"9a59904b-af0a-4032-a0d7-e3b7a98e5907","added_by":"auto","created_at":"2026-03-11 12:24:54","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":3440479,"visible":true,"origin":"","legend":"\u003cp\u003eThe nomogram model for predicting the prognosis in IgAN.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8938552/v1/bdc3db02a258aa4424921367.png"},{"id":104405701,"identity":"accbcd06-edf6-47c5-a114-d4f8fe7a08e3","added_by":"auto","created_at":"2026-03-11 12:23:38","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":298542,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operating characteristic curve of the prediction model.\u003c/p\u003e\n\u003cp\u003eNotes. (A) Receiver operating characteristic curve of the 3-year prediction model. (B) Receiver operating characteristic curve of the 5-year prediction model. (C) Receiver operating characteristic curve of the 8-year prediction model.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-8938552/v1/b35c86dc57a2a857f74f19fd.png"},{"id":104338139,"identity":"b31695cd-54e6-4c99-9f53-170bab7688e8","added_by":"auto","created_at":"2026-03-10 16:18:16","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":286591,"visible":true,"origin":"","legend":"\u003cp\u003eCalibration of the nomogram for renal prognosis in IgAN.\u003c/p\u003e\n\u003cp\u003eNotes. The x-axis shows the predicted probability of endpoint event in IgAN, and the y-axis shows the observed probability of endpoint event in IgAN. (A) Nomogram of 3-year calibrated risk of endpoint event in IgAN. (B) Nomogram of 5-year calibrated risk of endpoint event in IgAN. (C) Nomogram of 8-year calibrated risk of endpoint event in IgAN.\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-8938552/v1/93fe0a4f8ce9fa0922133caf.png"},{"id":104338136,"identity":"df084b84-804c-491f-b320-35440b5af0dd","added_by":"auto","created_at":"2026-03-10 16:18:15","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":433874,"visible":true,"origin":"","legend":"\u003cp\u003eThe ROC of IIgAN-PRT models with and without FPE.\u003c/p\u003e","description":"","filename":"Figure8.png","url":"https://assets-eu.researchsquare.com/files/rs-8938552/v1/e6520171a2688d9350c56371.png"},{"id":104338138,"identity":"b6300f11-b479-4bfb-97fd-9609bedec840","added_by":"auto","created_at":"2026-03-10 16:18:15","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":765050,"visible":true,"origin":"","legend":"\u003cp\u003eRemission rates at 3, 6, 12 months after treatment.\u003c/p\u003e\n\u003cp\u003eNotes. *P\u0026lt;0.05 comparison between the three groups; #P\u0026lt;0.05 versus 3-month remission rate.\u003c/p\u003e","description":"","filename":"Figure9.png","url":"https://assets-eu.researchsquare.com/files/rs-8938552/v1/9439242ae62f47e62cfcfda6.png"},{"id":109481533,"identity":"68cc8dc6-6d8f-4024-a7d5-1695a2c22bbe","added_by":"auto","created_at":"2026-05-18 15:11:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8845449,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8938552/v1/5a2a147f-7e50-412b-b88b-29136d956477.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Significance of Foot Process Effacement in Renal Prognosis and Response to Treatment in IgA Nephropathy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIgA nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis globally and constitutes a common cause of severe renal failure in young adults [1]. According to reports, the annual incidence of IgAN ranges from 0.2 to 5 cases per 100,000 individuals, with the highest prevalence observed in East Asian countries [2]. The potential pathogenesis of IgAN has been analyzed at the sub-molecular level, primarily involving aberrant synthesis and glycosylation of IgA1, leading to elevated levels of galactose-deficient IgA1 (gd-IgA1) in circulation. Multiple ethnic, genetic and environmental factors jointly contribute to and regulate renal injury [3-4]. As many as 30% to 40% of individuals with IgAN may progress to end-stage renal disease (ESRD) within 20 to 30 years following diagnosis [5]. Although research has found that histological features (such as MEST-C score), proteinuria and hypertension are risk factors for prognosis, increasing evidence indicates that foot process effacement (FPE) plays a crucial role in the progression of IgAN [6-7]. According to reports, FPE impacts renal survival in patients with kidney failure through both direct effects and indirect (mediated) effects via albuminuria [8].\u003c/p\u003e\n\u003cp\u003ePodocytes are highly specialized epithelial cells characterized by numerous interdigitating foot processes; together with the glomerular basement membrane (GBM) and endothelial cells, they maintain the glomerular filtration barrier [9]. One of the most typical morphological changes in the early stage of podocyte injury is FPE, which is characterized by swelling, retraction and bending of podocyte processes, thereby disrupting the typical interlacing pattern [10]. Studies have found that in glomerular diseases such as focal segmental glomerulosclerosis (FSGS) and lupus nephritis, the severity of FPE correlates with renal function decline and disease recurrence [11-12]. Nevertheless, the association between FPE levels and the clinical outcomes in IgAN remains unclear. To assess the impact of FPE on the renal prognosis and treatment response in patients with IgAN, we undertook this investigation.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 2,211 patients with biopsy-confirmed IgAN were enrolled from Hangzhou Hospital of Traditional Chinese Medicine between October 2014 and November 2023. Among them, 705 patients were excluded for the following reasons: 97 patients were under 18 years of age; 302 patients had a follow-up period of less than 12 months; 298 patients had secondary IgAN, chronic systemic diseases, active infections, or allergic diseases; and 8 patients lacked clinical or pathological data. The study was approved by the Ethics Committee of Hangzhou Hospital of Traditional Chinese Medicine and conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from all participants. (No. 2024KLL230).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical date\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical data were retrospectively collected at the time of renal biopsy, including age, gender, body mass index (BMI), hemoglobin (Hb), albumin (ALB), total cholesterol (TCH), triglycerides (TG), low-density lipoprotein (LDL), high-sensitivity C-reactive protein (H-CRP), uric acid (UA), immunoglobulin G (IgG), immunoglobulin A (IgA), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), urine red blood cell (uRBC), 24-hour urinary total protein (24h UTP), and treatment plan. During the clinical follow-up period, the clinical data obtained from repeated examinations were regularly collected and continuously tracked until August 2025 or the occurrence of an endpoint event. eGFR was calculated using the adult CKD-EPI 2009 equation [13].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistopathology\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll biopsy specimens were independently reviewed by two renal pathologists who were blinded to the clinical data. Renal biopsy specimens were processed for light microscopy using hematoxylin and eosin, periodic acid-Schiff, periodic acid-methenamine silver, and Masson’s trichrome staining, as well as immunofluorescence and electron microscopy. Renal histological lesions were assessed using the MEST-C score [14]. The mesangial hypercellularity of glomeruli was scored as M0 (≤50%) or M1 (\u0026gt;50%). Endocapillary hypercellularity was classified as E0 (absent) or E1 (present). Segmental glomerulosclerosis was recorded as S0 (absent) or S1 (present). Tubular atrophy and interstitial fibrosis were graded as T0 (≤25%), T1 (26–50%), or T2 (\u0026gt;50%). Crescentic lesions were categorized as C0 (absent), C1 (\u0026lt;25%), or C2 (≥25%).\u003c/p\u003e\n\u003cp\u003ePodocyte FPE was defined as the loss or obliteration of the slit-like spaces between adjacent podocyte foot processes. The extent of FPE was assessed using the mean foot process width, as determined by the method of Gundersen, Seefeldt, and Osterby [15]. Each patient was observed under a visualized electron microscope for approximately 1-2 complete glomeruli, and each complete glomerulus contains approximately 5-8 capillary loops. The severity of FPE was assessed through a semi-quantitative visual inspection. The evaluation criteria were the proportion of FPE in the capillary loops of the glomerulus, and it was classified into five groups based on the severity of FPE: \u0026lt;25%, 25%–49%, 50%–74%, 75%–89%, and ≥90%. In this study, we ultimately divided the enrolled IgAN patients into three groups based on the percentage of FPE in the capillary loops: mild (\u0026lt;50%), moderate (50%–74%), and severe (≥75%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEndpoint event\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary renal endpoint event was defined as either a 50% decline in eGFR or ESRD, which was characterized by an eGFR \u0026lt;15 mL/min/1.73m²\u0026nbsp;or the initiation of kidney replacement therapy, including hemodialysis, peritoneal dialysis, or kidney transplantation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTherapeutic response\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 1506 enrolled patients, individuals with complete follow-up data (including 24h UTP and Scr) at 3, 6, and 12 months after treatment initiation were selected for the evaluation of therapeutic efficacy (Figure 1). Immunosuppressive therapy (IST) was defined as treatment with steroids or immunosuppressants, irrespective of treatment duration or dosage. Complete clinical remission (CR) was defined as patients with 24h UTP ≤ 0.3 g/d and stable renal function (eGFR reduction ≤ 30%). Partial remission (PR) was defined as a \u0026gt;50% reduction in proteinuria from baseline, accompanied by 24h UTP \u0026lt; 1g/24h and stable renal function, without meeting the CR criteria. Non-response (NR) refers to cases that do not meet the CR or PR criteria.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were conducted using IBM SPSS software (version 27.0) and R statistical software (version 4.5.1). The Python programming language (version 3.9) was used to plot the graphs. Continuous distributions were presented as the mean ± standard deviation and were analyzed using an unpaired \u003cem\u003et\u003c/em\u003e test or one-way ANOVA, whereas skewed distributions were displayed as the median with interquartile range and were analyzed using the Kruskal-Wallis \u003cem\u003eH\u003c/em\u003e test or the nonparametric Mann-Whitney \u003cem\u003eU\u003c/em\u003e test. Categorical variables were presented as frequencies, and comparisons were performed using the\u0026nbsp;\u003cstrong\u003eχ²\u003c/strong\u003e test or Fisher’s exact tests. Spearman correlation analysis was conducted to examine the relationship between FPE and clinicopathological variables. The Kaplan-Meier survival curve and Log-rank test were applied to compare renal survival across different levels of FPE. Cox regression models were employed to conduct subgroup analyses. Cox regression was performed to identify independent prognostic factors associated with IgAN outcomes. A nomogram prediction model was constructed through a stepwise approach to identify optimal combinations of predictors for estimating the prognosis of IgAN. The predictive accuracy of the nomograms was assessed using the concordance index (C-index) and receiver operating characteristic (ROC) curve analysis, and the discriminative ability was validated through calibration plots. P \u0026lt; 0.05 was considered significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective analysis included 2,211 individuals diagnosed with IgAN through kidney biopsy at Hangzhou Hospital of Traditional Chinese Medicine from October 2014 to November 2023. Based on the predefined criteria for inclusion and exclusion in the study, a total of 1,506 patients were included in the final analysis (as shown in Fig. 1). The study cohort comprised 603 (40%) males and 903 (60%) females, with a median age of 44 (36, 54) years. Patients were categorized into three groups according to the degree of FPE. The largest proportion was classified as the mild group (1,026 patients, 68.1%), followed by the moderate group (316 patients, 21.0%), while the severe group included only 164 patients (10.9%). The baseline data analysis revealed that, except for Hb, there were statistically significant differences in all other clinical indicators among the groups. The severe group had the highest age and the largest proportion of male patients. Compared with the other two groups, the BMI, TCH, TG, LDL, H-CRP, UA, Scr, and 24h UTP of the severe group patients were higher, while ALB and eGFR were lower, and the differences were statistically significant. The MESTC score of renal pathology showed that in the severe group, the E lesions, T lesions and C lesions were more severe (P \u0026lt; 0.05). Patients with higher foot process effacement levels were more likely to receive IST and exhibited an increased risk of endpoint event, as shown in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation of FPE with clinical and pathological characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Spearman correlation analysis was performed to evaluate the associations between variables, and the results revealed that FPE was significantly positively correlated with age (r = 0.107, P \u0026lt; 0.001), BMI (r = 0.108, P \u0026lt; 0.001), TCH (r = 0.208, P \u0026lt; 0.001), TG (r = 0.217, P \u0026lt; 0.001), LDL (r = 0.212, P \u0026lt; 0.001), UA (r = 0.169, P \u0026lt; 0.001) and 24h UTP (r = 0.456, P \u0026lt; 0.001), while it was significantly negatively correlated with gender (r = -0.078, P = 0.002), ALB (r = -0.309, P \u0026lt; 0.001), IgG (r = -0.209, P \u0026lt; 0.001), and eGFR (r = -0.297, P \u0026lt; 0.001). Furthermore, with respect to the Oxford classification of renal pathology, FPE was positively correlated with the Oxford classifications E, S, T, and C (r = 0.070, P = 0.009;r = 0.081, P = 0.002;r = 0.236, P \u0026lt; 0.001;r = 0.120, P \u0026lt; 0.001). (Figure 2)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociations of FPE with risk of renal survival rate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the median follow-up of 44.80 (26.98, 68.83) months, a total of 103 patients reached the endpoint event, accounting for 6.8%. Moreover, there were significant differences in the event occurrence rates among patients with different degrees of FPE: mild (4.0%), moderate (9.4%), and severe (18.9%)(as shown in Table 1).\u003c/p\u003e\n\u003cp\u003eThe Kaplan-Meier analysis indicated that increased severity of foot process effacement was significantly associated with an increased risk of renal failure (log-rank test, P \u0026lt; 0.01; shown in Fig. 3). The mean kidney survival time of patients in the severe group (81.78 months, 95% CI: 75.17 - 88.38) was significantly shorter than that in the mild group (103.87 months, 95% CI: 102.14-105.60) and the moderate group (97.13 months, 95% CI : 93.80 - 100.47).\u003c/p\u003e\n\u003cp\u003eIn unadjusted Cox analysis, the hazard of poor renal prognosis in the mild group was lower than that in the moderate group (HR: 2.053, 95% CI: 1.284 - 3.285) and severe group (HR: 5.043, 95% CI: 3.162 - 8.043)(P \u0026lt; 0.001). To minimize the impact of other related factors, we constructed three models incorporating relevant clinical, pathological, and treatment variables. As depicted in Models 1,2 and 3, the multivariate Cox regression analysis manifested that the high level of foot process effacement was an independent risk factor for renal progression even after adjustment for clinical parameters (gender, Hb, Alb, TG, LDL, UA, 24h UTP and eGFR) (adjusted HR: 2.451, 95% CI: 1.425 - 4.217, P = 0.002) and combined with pathologic lesions (Oxford MEST-C) (adjusted HR: 3.551, 95% CI:1.477-8.538, P = 0.009) and combined with treatment (adjusted HR: 3.688, 95% CI: 1.548-8.784, P = 0.009), as shown in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to gender (male / female), age (≤ 45 / \u0026gt; 45), BMI (≤ 26 / \u0026gt; 26), ALB (≤ 38 / \u0026gt; 38), UA (≤ 360 / \u0026gt; 360), TCH (≤ 4.5 / \u0026gt; 4.5), LDL (≤ 2.8 / \u0026gt; 2.8), and steroid/immunosuppressants (NO / Yes), we performed a series of subgroup analyses to evaluate potential heterogeneity among different groups. The results showed that for male patients aged ≤ 45 years, severe FPE was an independent risk factor for adverse renal outcomes (HR: 6.943, 95% CI: 2.076 - 23.221, P = 0.002; HR: 5.717, 95% CI: 1.295 - 25.239, P = 0.021). Interestingly, in female patients aged \u0026gt; 45 years, this risk was significantly reduced (HR: 0.660, 95% CI: 0.091 - 4.774, P = 0.681; HR: 2.730, 95% CI: 0.579 - 12.877, P = 0.204) as shown in Fig. 4. This suggests that for male patients aged 45 or younger, we should pay more attention to the level of FPE.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEstablish and validate the nomogram prognostic model\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThrough Cox regression analysis, we selected gender,\u0026nbsp;24h\u0026nbsp;UTP, eGFR, FPE, Oxford classification scores S and T to construct a nomogram prediction model for evaluating the prognosis of IgAN (Figure 5). The C-index of the nomogram model was 0.93, and the areas under the receiver operating characteristic curve (AUC) at 3, 5, and 8 years were 0.958, 0.964, and 0.892 respectively (Figure 6), demonstrating its high accuracy in predicting adverse outcomes in patients with IgAN. In addition, we also evaluated the calibration of the nomogram model using calibration curves (Figure 7). The graphs revealed good agreement between predicted and observed outcomes, further validating the reliability of the nomogram model in predicting the prognosis of patients with IgAN.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMultivariate ROC Curve Associated with FPE and the IIgAN-PRT Model\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMultivariable logistic regression analyses were conducted\u0026nbsp;by incorporating the relevant parameters from the original IIgAN-PRT models, both with and without FPE. The ROC curve demonstrated a higher AUC for the model with FPE (AUC: 0.977) compared to the model without FPE (AUC: 0.976), as shown in Fig. 8.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImpact of FPE levels on the response to treatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo further clarify the influence of FPE severity on the\u0026nbsp;response to treatment, 288 patients were selected for analysis as per the requirements. The results showed that in patients not receiving IST, the cumulative remission rates (CR+PR) showed an increasing trend across the mild, moderate, and severe FPE groups over the treatment period. However, at the 12-month mark, the remission rate in the severe FPE group remained significantly lower than those in the mild and moderate groups (P=0.023). In contrast, among patients treated with IST, the three FPE severity groups also exhibited a general trend toward higher remission rates over time. A key finding was that at 12 months, the severe FPE group demonstrated a marked improvement in the cumulative remission rate, which was comparable to the rates observed in the mild and moderate groups, with no statistically significant difference (P=0.608) (Table 3, Figure 9).\u003c/p\u003e\n\u003cp\u003eThese results indicate that in the absence of IST, FPE severity was an important factor influencing treatment response, with more severe FPE associated with worse the treatment outcomes. For patients who received IST, it can improve the treatment response of patients with severe FPE over a long period (12 months) and reduce the differences in treatment responses among patients with different degrees of FPE severity.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIgAN represents the most common form of primary chronic glomerulopathy globally. The immune complexes composed of Gd-IgA1 and its specific autoantibodies deposit in the mesangial area, playing a key role in the pathogenesis of IgAN [16]. The deposition of immune complexes in the mesangial region induces mesangial cell proliferation, which subsequently exerts pathological effects on other renal cells, including podocytes and tubular epithelial cells [17]. Podocyte injury can further lead to podocyte detachment, podocyte hypertrophy, and foot process effacement [10]. Previous studies indicates that podocytopathy caused by podocyte loss can lead to segmental sclerosis, which is associated with the severity of IgAN [18, 19].\u003c/p\u003e\n\u003cp\u003eIn a retrospective study involving 976 patients with IgAN, Guo Y et al. reported that participants with severe FPE were more likely to have higher 24hUPE, MESTC scores, and lower serum albumin, eGFR [20]. In our study, we also confirmed that patients with severe FPE had more clinical and pathological manifestations, and more patients receive immunosuppressive therapy. The incidence of endpoint events was significantly higher in the severe FPE group compared to the other two groups. K-M survival analysis demonstrated a statistically significant difference in the mean renal survival time among the three groups, with the severe FPE group showing a notably shorter renal survival time compared to the other two groups. Multivariate Cox regression analysis further suggested that FPE may serve as an independent risk factor for renal prognosis in IgAN, which is consistent with the research results of Gao L et al. [21].\u003c/p\u003e\n\u003cp\u003ePodocytes are terminally differentiated epithelial cells. A typical feature of FPE is the rearrangement of the podocyte cytoskeleton, which leads to the retraction and flattening of foot processes [22]. FPE is not merely a passive marker of injury but an active participant in the pathogenesis of IgAN. This structural derangement of FPE disrupts the integrity of the slit diaphragm, the crucial size-selective filtration barrier. Consequently, the glomerular permeability to proteins increases, manifesting clinically as proteinuria, a well-established driver of tubulointerstitial injury and fibrosis, and also the core mechanism by which FPE leads to the progression of IgAN [23, 24]. Furthermore, sustained injury triggers podocyte phenotypic changes, apoptosis, and eventual detachment, leading to irreversible glomerulosclerosis [25]. The degree of FPE observed on electron microscopy thus serves as a direct histomorphometric correlate of podocyte stress and loss. The research by Lee JH et al. indicated that proteinuria was a significant risk factor for the progression of IgAN and was positively correlated with the severity of foot process effacement [26]. A single-center retrospective study involving 107 patients with IgAN revealed that, beyond the established MEST-C score, ultrastructural lesions, specifically podocyte lesions, were associated with a lower renal survival rate, underscoring the prognostic value of lesions detected by transmission electron microscopy [27]. These findings confirm our conclusion, indicating that FPE is not just a secondary phenomenon but also a critical driver of glomerular injury, independently influencing the clinical course of IgAN.\u003c/p\u003e\n\u003cp\u003eTo explore whether the effect of FPE varies among different clinicopathological characteristics, we conducted a subgroup analysis. The results showed that FPE confers a higher risk in male patients aged ≤ 45 years. In addition, we incorporated gender, 24h UTP, eGFR, FPE, Oxford classification scores S and T into the assessment parameters for the first time and proposed a nomogram model. The model revealed that more severe FPE was associated with higher scores and an increased risk of endpoint events in IgAN patients at 3, 5, and 8 years. The C-index, AUC, and calibration plots further validated the reliability of the nomogram model. By comparing the predictive performance of the IIgANPRT model with and without FPE, we found that the inclusion of FPE improved the model's assessment capability. These findings suggest that FPE may serve as a predictor of renal function progression in IgAN.\u003c/p\u003e\n\u003cp\u003eGlucocorticoids and other immunosuppressants are known to exert potent anti-inflammatory and immunomodulatory effects and are the main therapeutic strategies for podocytopathy. These drugs directly act on podocytes by regulating some cytokines and multiple signaling pathways related to cytoskeletal stability, cell maturation and survival [28, 29]. Specifically, glucocorticoids such as dexamethasone have been shown to stabilize the podocyte actin cytoskeleton by modulating the activity of small GTPases like RhoA, which are critical for maintaining the structural integrity of foot processes [30]. Furthermore, mycophenolate mofetil can inhibit the early abnormal hypertrophy and apoptosis of podocytes by modulating the expression of cell cycle related proteins p27\u003csup\u003ekip1\u003c/sup\u003e, p21\u003csup\u003ecip1\u003c/sup\u003e, and apoptosis related genes (such as bax, bcl-2 and cleaved caspase-3) [31]. Beyond its established role as a structural correlate of prognosis, our findings shed new light on the influence of FPE on therapeutic responsiveness in IgAN, particularly to immunosuppressive therapy. We demonstrated that in patients not receiving IST, the severity of FPE was a dominant factor determining therapeutic outcome, with more extensive effacement predicting a poorer response. This underscores the limitation of conservative treatment alone when confronted with severe podocyte injury. however, our data revealed that IST can reverse this trend. For patients receiving IST, we observed that the treatment could continuously improve the clinical response of patients with severe podocyte effacement at 12 months. Importantly, immunosuppressive therapy effectively diminished the previously observed disparities in treatment responses between patients with varying severities of FPE. This finding is supported by prior studies, where Wang Y et al. found that corticosteroids were more effective in reducing proteinuria and improving renal function in IgAN patients with active inflammatory lesions—pathological changes frequently accompanied by podocyte injury[32].\u003c/p\u003e\n\u003cp\u003eSeveral limitations of this study should be acknowledged. Firstly, its retrospective and single-center design may have introduced selection bias and limited the generalizability of the study results. Secondly, the assessment of FPE, though performed by experienced pathologists, remains semi-quantitative and subjective; the lack of a universally standardized, quantitative method for evaluating the degree of FPE is a notable constraint. Lastly, the follow-up duration, while substantial, may still be insufficient to capture the very long-term renal outcomes in a chronic disease like IgAN.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, FPE, as a histopathological marker, may be an independent predictor of the progression to ESRD in IgAN patients, especially when the patients are male and aged \u0026le; 45 years. The constructed nomogram model incorporating FPE alongside key clinical parameters provides a practical tool for individualized risk stratification. Importantly, our findings offer novel insights into treatment, suggesting that IST can effectively overcome the adverse impact of severe FPE on treatment response. This indicates that for such patients, IST is a necessary intervention, and its course should be maintained for at least 12 months. Therefore, assessment of FPE should be integrated into the routine pathological evaluation of IgAN to guide both prognostic counseling and therapeutic decision-making.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eFPE \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;foot process effacement\u003c/p\u003e\n\u003cp\u003eIgAN \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; IgA nephropathy\u003c/p\u003e\n\u003cp\u003eC-index \u0026nbsp; \u0026nbsp; \u0026nbsp; concordance index\u003c/p\u003e\n\u003cp\u003eROC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Receiver Operating Characteristic\u003c/p\u003e\n\u003cp\u003eAUC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;area under the receiver operating characteristic curve\u003c/p\u003e\n\u003cp\u003eESRD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; end-stage renal disease\u003c/p\u003e\n\u003cp\u003eIST \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; immunosuppressive therapy\u003c/p\u003e\n\u003cp\u003egd-IgA1 \u0026nbsp; \u0026nbsp; \u0026nbsp; galactose-deficient IgA1\u003c/p\u003e\n\u003cp\u003eGBM \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; glomerular basement membrane\u003c/p\u003e\n\u003cp\u003eFSGS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; focal segmental glomerulosclerosis\u003c/p\u003e\n\u003cp\u003eBMI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;body mass index\u003c/p\u003e\n\u003cp\u003eHb \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; hemoglobin\u003c/p\u003e\n\u003cp\u003eALB \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;albumin\u003c/p\u003e\n\u003cp\u003eTCH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;total cholesterol\u003c/p\u003e\n\u003cp\u003eTG \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; triglycerides\u003c/p\u003e\n\u003cp\u003eLDL \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;low-density lipoprotein\u003c/p\u003e\n\u003cp\u003eH-CRP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;high-sensitivity C-reactive protein\u003c/p\u003e\n\u003cp\u003eUA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; uric acid\u003c/p\u003e\n\u003cp\u003eIgG \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; immunoglobulin G\u003c/p\u003e\n\u003cp\u003eIgA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; immunoglobulin A\u003c/p\u003e\n\u003cp\u003eScr \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; serum creatinine\u003c/p\u003e\n\u003cp\u003eeGFR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; estimated glomerular filtration rate\u003c/p\u003e\n\u003cp\u003euRBC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; urine red blood cell\u003c/p\u003e\n\u003cp\u003e24h UTP \u0026nbsp; \u0026nbsp; \u0026nbsp;24-hour urinary total protein\u003c/p\u003e\n\u003cp\u003eCR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; complete clinical remission\u003c/p\u003e\n\u003cp\u003ePR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; partial remission\u003c/p\u003e\n\u003cp\u003eNR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; non-response\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all clinicians at the Department of Nephrology, Hangzhou TCM Hospital Afliated to Zhejiang Chinese Medical University for their efforts in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKX: Writing - original draft, Methodology, Investigation, Ethics approval acquisition. XJ: Writing - original draft, Methodology, Software. HL and AW: patient follow-up. YY and JY: Writing - original draft. YD and SZ: Data curation. DY: Funding acquisition, Writing - review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHangzhou Medical and Health Science and Technology Project under Grant No.ZD20240017; Medical Scientific Research Foundation of Zhejiang Province under Grant No.2025KY154; Medical Scientific Research Foundation of Zhejiang Province under Grant No.2025KY1146; The Construction fund of Key medical Disciplines of Hangzhou under Grand No.2025HZGF12, 2025HZPY05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures carried out in studies involving human participants comply with the ethical standards of the Ethics Committee of Hangzhou TCM Hospital affiliated to Zhejiang Chinese Medical University, and follow the Helsinki Declaration and its later amendments or comparable ethical standards (No. 2024KLL230). \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eStamellou E, Seikrit C, Tang SCW, et al. IgA nephropathy. Nat Rev Dis Primers. 2023;9:67. https://doi.org/10.1038/s41572-023-00476-9.\u003c/li\u003e\n\u003cli\u003ePattrapornpisut P, Avila-Casado C, Reich HN. IgA Nephropathy: Core Curriculum. 2021. Am J Kidney Dis 2021;78:429-441. https://doi.org/10.1053/j.ajkd.2021.01.024.\u003c/li\u003e\n\u003cli\u003eGuti\u0026eacute;rrez E, Carvaca-Font\u0026aacute;n F, Luzardo L, et al. A Personalized Update on IgA Nephropathy: A New Vision and New Future Challenges. Nephron. 2020;144:555-571. https://doi.org/10.1159/000509997.\u003c/li\u003e\n\u003cli\u003eSuzuki H, Kiryluk K, Novak J, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011;22:1795-803. https://doi.org/10.1681/ASN.2011050464.\u003c/li\u003e\n\u003cli\u003eLai KN, Tang SC, Schena FP, et al. IgA nephropathy. Nat Rev Dis Primers. 2016;2:16001. https://doi.org/10.1038/nrdp.2016.1.\u003c/li\u003e\n\u003cli\u003eDuval A, Caillard S, Fr\u0026eacute;meaux-Bacchi V. The complement system in IgAN: mechanistic context for therapeutic opportunities. Nephrol Dial Transplant. 2023;38:2685-2693. https://doi.org/10.1093/ndt/gfad140.\u003c/li\u003e\n\u003cli\u003eLee JH, Jang SH, Cho NJ, et al. Severity of foot process effacement is associated with proteinuria in patients with IgA nephropathy. Kidney Res Clin Pract. 2020;39:295-304. https://doi.org/10.23876/j.krcp.20.017.\u003c/li\u003e\n\u003cli\u003eWittig M, Verma A, Bellavia A, et al. The Associations of Foot Process Effacement with Kidney Histopathologic Lesions and Disease Progression. Kidney360. 2026;7:72-80. https://doi.org/10.34067/KID.0000000894.\u003c/li\u003e\n\u003cli\u003evan den Berg JG, van den Bergh Weerman MA, Assmann KJ, et al. Podocyte foot process effacement is not correlated with the level of proteinuria in human glomerulopathies. Kidney Int. 2004;66:1901-1906. https://doi.org/10.1111/j.1523-1755.2004.00964.x.\u003c/li\u003e\n\u003cli\u003eKriz W, Shirato I, Nagata M, et al. The podocyte\u0026apos;s response to stress: the enigma of foot process effacement. Am J Physiol Renal Physiol. 2013;304:F333-F347. https://doi.org/10.1152/ajprenal.00478.2012.\u003c/li\u003e\n\u003cli\u003eSethi S, Zand L, Nasr SH, et al. Focal and segmental glomerulosclerosis: clinical and kidney biopsy correlations. Clin Kidney J. 2014;7:531-537. https://doi.org/10.1093/ckj/sfu100.\u003c/li\u003e\n\u003cli\u003eGuo M, Xie X, Lin W, et al. Association of podocyte injury with clinical features and prognosis in patients with mesangial proliferative lupus nephritis. Lupus. 2023;32:231-238. https://doi.org/10.1177/09612033221141269.\u003c/li\u003e\n\u003cli\u003eLevey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604-12. https://doi.org/10.7326/0003-4819-150-9-200905050-00006.\u003c/li\u003e\n\u003cli\u003eTrimarchi H, Barratt J, Cattran DC, et al. Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017;91:1014-1021. https://doi.org/10.1016/j.kint.2017.02.003.\u003c/li\u003e\n\u003cli\u003eGundersen HJ, Seefeldt T, Osterby R. Glomerular epithelial foot processes in normal man and rats. Distribution of true width and its intra- and inter-individual variation. Cell Tissue Res. 1980;205:147-155. https://doi.org/10.1007/BF00234450.\u003c/li\u003e\n\u003cli\u003eRobert T, Berthelot L, Cambier A, et al. Molecular Insights into the Pathogenesis of IgA Nephropathy. Trends Mol Med. 2015;21:762-775. https://doi.org/10.1016/j.molmed.2015.10.003.\u003c/li\u003e\n\u003cli\u003eFloege J, Moura IC, Daha MR. New insights into the pathogenesis of IgA nephropathy. Semin Immunopathol. 2014;36:431-442. https://doi.org/10.1007/s00281-013-0411-7.\u003c/li\u003e\n\u003cli\u003eEl Karoui K, Hill GS, Karras A, et al. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies. Kidney Int. 2011;79:643-654. https://doi.org/10.1038/ki.2010.460.\u003c/li\u003e\n\u003cli\u003eHill GS, Karoui KE, Karras A, et al. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. I. Immunohistochemical studies. Kidney Int. 2011;79:635-642. https://doi.org/10.1038/ki.2010.466.\u003c/li\u003e\n\u003cli\u003eGuo Y, Ren Y, Shi S, et al. Effects of Podocyte Foot Process Effacement on Kidney Prognosis and Response to Immunosuppressive Therapy in IgA Nephropathy. Kidney Med. 2025;7:101049. https://doi.org/10.1016/j.xkme.2025.101049.\u003c/li\u003e\n\u003cli\u003eGao L, Zhang X, Yu D, et al. The importance of the degree of foot process effacement in evaluating the prognosis of IgA nephropathy. Int Urol Nephrol. 2025;57:3417-3426. https://doi.org/10.1007/s11255-025-04529-8.\u003c/li\u003e\n\u003cli\u003eAltintas MM, Agarwal S, Sudhini Y, et al. Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders. Annu Rev Pathol. 2025;20:329-353. https://doi.org/10.1146/annurev-pathol-051220-092001.\u003c/li\u003e\n\u003cli\u003eShankland SJ. The podocyte\u0026apos;s response to injury: role in proteinuria and glomerulosclerosis. Kidney Int. 2006;69:2131-2147. https://doi.org/10.1038/sj.ki.5000410.\u003c/li\u003e\n\u003cli\u003eXu L, Yang HC, Hao CM, et al. Podocyte number predicts progression of proteinuria in IgA nephropathy. Mod Pathol. 2010;23:1241-1250. https://doi.org/10.1038/modpathol.2010.110.\u003c/li\u003e\n\u003cli\u003eLu CC, Wang GH, Lu J, et al. Role of Podocyte Injury in Glomerulosclerosis. Adv Exp Med Biol. 2019;1165:195-232. https://doi.org/10.1007/978-981-13-8871-2_10.\u003c/li\u003e\n\u003cli\u003eLee JH, Jang SH, Cho NJ, et al. Severity of foot process effacement is associated with proteinuria in patients with IgA nephropathy. Kidney Res Clin Pract. 2020;39:295-304. https://doi.org/10.23876/j.krcp.20.017.\u003c/li\u003e\n\u003cli\u003eTerinte-Balcan G, Stancu S, Zugravu A, et al. Prognostic role of glomerular electron microscopy lesions in IgA nephropathy: \u0026quot;the devil is in the details\u0026quot;. J Nephrol. 2023;36:2233-2243. https://doi.org/10.1007/s40620-023-01744-3.\u003c/li\u003e\n\u003cli\u003eKopp JB, Anders HJ, Susztak K, et al. Podocytopathies. Nat Rev Dis Primers. 2020;6:68. https://doi.org/10.1038/s41572-020-0196-7.\u003c/li\u003e\n\u003cli\u003eSch\u0026ouml;nenberger E, Ehrich JH, Haller H, et al. The podocyte as a direct target of immunosuppressive agents. Nephrol Dial Transplant. 2011;26:18-24. https://doi.org/10.1093/ndt/gfq617\u003c/li\u003e\n\u003cli\u003eWelsh GI, Saleem MA. The podocyte cytoskeleton--key to a functioning glomerulus in health and disease. Nat Rev Nephrol. 2011;8:14-21. https://doi.org/10.1038/nrneph.2011.151.\u003c/li\u003e\n\u003cli\u003eLv W, Lou J, Zhang Y, et al. Mycophenolate mofetil inhibits hypertrophy and apoptosis of podocyte in vivo and in vitro. Int J Clin Exp Med. 2015;8:19781-19790.\u003c/li\u003e\n\u003cli\u003eWang Y, Huang N, Wang Y, et al. Comparative analysis between the safety and efficacy of oral corticosteroids versus corticosteroids pulse therapies in IgA nephropathy. Ren Fail. 2023;45:2255683. https://doi.org/10.1080/0886022X.2023.2255683.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 Characteristics of different degree of FPE in the study population.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"671\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 159px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 117px;\"\u003e\n \u003cp\u003eTotal(n=1506)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 341px;\"\u003e\n \u003cp\u003eFoot process effacement level\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eMild(n=1026)\u003c/p\u003e\n \u003cp\u003e\u0026lt;50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eModerate(n=316)\u003c/p\u003e\n \u003cp\u003e50-74%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eSevere(n=164)\u003c/p\u003e\n \u003cp\u003e\u0026ge;75%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e44(36,54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e43(36,53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e44(36,54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e48(37.75,60.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eMale, n（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e603(40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e386(37.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e135(42.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e82(50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eBMI, kg/m2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e23.05(20.93,25.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e22.67(20.81,25.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e23.34(20.87,25.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e24.22(22.11,26.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eHb,g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e125.67\u0026plusmn;18.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e126.20\u0026plusmn;17.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e125.07\u0026plusmn;19.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e123.48\u0026plusmn;20.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eALB, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e38.30(35.50,40.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e38.90(36.30,41.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e37.60(34.30,39.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e34.60(28.85,38.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eTCH, mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e4.67(4.06,5.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e4.58(4.01,5.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e4.75(4.06,5.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e5.34(4.35,6.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eTG, mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1.33(0.92,1.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.21(0.85,1.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e1.36(0.97,1.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e1.77(1.39,2.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eLDL, mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e2.91(2.39,3.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e2.85(2.33,3.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e2.91(2.39,3.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e3.38(2.71,4.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eH-CRP, mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1.00(0.48,2.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.96(0.47,2.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e1.07(0.50,2.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e1.32(0.52,3.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eUA, \u0026mu;mol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e355(291.5,428.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e343.5(282,421)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e371(294,445)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e399.5(344,474.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eScr, \u0026mu;mol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e79(61,109)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e75(58,98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e85(64,117)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e108(78,156)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e24h UTP, g/d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e0.95(0.49,1.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.69(0.38,1.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e1.52(0.85,2.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e2.51(1.53,4.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eeGFR,（ml/min)/1.73m2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e85.30(60.75,108.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e91.30(69.55,111.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e77.20(53.20,104.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e53.90(39.00,77.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 671px;\"\u003e\n \u003cp\u003eOxford classification\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eM0/M1(% of M1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e5/1501(99.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e4/1022(92.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0/316(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e1/163(99.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.463\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eE0/E1(% of E1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1006/500(33.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e717/309(30.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e198/118(37.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e91/73(44.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eS0/S1(% of S1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e373/1133(75.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e253/773(75.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e81/235(74.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e39/125(76.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.896\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eT0/T1/T2(% of [T1+T2])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1059/359/88(29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e797/204/25(22.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e195/92/29(38.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e67/63/34(59.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eC0/C1/C2(% of [C1+C2])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e930/448/128(38.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e644/314/68(37.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e190/86/40(39.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e96/48/20(41.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 671px;\"\u003e\n \u003cp\u003eTherapy,n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eNone steroid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1052(69.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e754(73.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e203(64.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e95(57.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eSteroid alone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e321(21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e209(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e74(23.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e38(23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003eSteroid+immunosuppressants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e133(8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e63(6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e39(12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e31(18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 671px;\"\u003e\n \u003cp\u003eEndpoint event, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003ehappen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e103(6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e42(4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e30(9.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e31(18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2\u0026nbsp;Multivariate Cox regression analysis FPE and renal outcomes.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"left\" width=\"105%\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003eUnivariate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003eModel 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003eModel 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003eModel 3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eHR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003eMild (\u0026le;50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e1.000(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1.000(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e1.000(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e1.000(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003eModerate(51-75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e2.053(1.284-3.285)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1.019(0.619-1.679)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e1.075(0.428-2.703)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e1.246(0.490-3.172)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003eSevere(＞75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e5.043(3.162-8.043)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e2.451(1.425-4.217)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e3.551(1.477-8.538)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e3.688(1.548-8.784)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003ep for trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNotes. Model 1:was adjusted for age, gender+clinic factors (Hb, Alb, TG, LDL, UA, 24h UTP and eGFR). Model 2:was adjusted for Model 1+Oxford classification(MEST-C). Model 3:was adjusted for Model 2+therapy. ALB, 24h UTP, and eGFR were transformed into binary variables with cutoff of 25, 1, and 45 respectively. Tubulointerstitial atrophy/interstitial fibrosis(T)was transformed into a binary variable of T0 and T1+T2. Crescent(C) was transformed into a binary variable of C0 and C1+C2.\u003c/p\u003e\n\u003cp\u003eAbbreviations: CI, confidence intervals; HR, hazard ratios\u003c/p\u003e\n\u003cp\u003eTable 3 Remission rates at 3, 6, 12 months after treatment.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"711\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 323px;\"\u003e\n \u003cp\u003eWithout IST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 323px;\"\u003e\n \u003cp\u003eIST\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eMild(N=104)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eModerate(N=46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eSevere(N=17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eMild(N=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003eModerate(N=35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eSevere(N=26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 332px;\"\u003e\n \u003cp\u003e3 months, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 268px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.109\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e45(43.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e8(17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e2(11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e23(38.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e9(25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3(11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e22(21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e13(28.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e6(35.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e12(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e10(28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e6(23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e37(35.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e25(54.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e9(52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e25(41.7) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e16(45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e17(65.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 332px;\"\u003e\n \u003cp\u003e6 months, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 268px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.027\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e49(47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e14(30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e5(29.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e26(43.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e11(31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e2(7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e28(26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e15(32.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e3(17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e14(23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e11(31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e9(34.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e27(26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e17(37.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e9(52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e20(33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e13(37.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e15(57.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 332px;\"\u003e\n \u003cp\u003e12 months, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 268px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.608\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e64(61.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e21(45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e5(29.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e32(53.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e15(42.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e13(50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e18(17.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e17(37.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e6(35.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e11(18.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e9(25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e8(30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e22(21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e8(17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e6(35.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e17(28.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e11(31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e5(19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\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":"IgA nephropathy, foot process effacement, prognosis, immunosuppressive therapy","lastPublishedDoi":"10.21203/rs.3.rs-8938552/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8938552/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study aimed to analyze the impact of foot process effacement (FPE) severity on prognosis and treatment response in IgA nephropathy (IgAN).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this retrospective study, 1,506 patients with biopsy-proven IgAN were categorized by FPE severity and followed for ≥12 months. The Kaplan-Meier survival and Cox regression analysis were performed to explore the relationship between FPE and adverse renal outcomes. The concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and the calibration curve were used to evaluate the nomogram model.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 1506 patients were included in this study and categorized into three groups according to the degree of FPE. Patients in the severe FPE group exhibited more severe clinical and pathological manifestations. Kaplan-Meier analysis revealed a significantly higher risk of renal failure in the severe FPE group compared to the others (log-rank P \u0026lt; 0.01). Multivariate Cox regression analysis further confirmed that FPE might be an independent risk factor for renal prognosis in IgAN (adjusted HR: 3.688, 95% CI: 1.548 - 8.784, P = 0.009). Subgroup analysis suggested that FPE level warranted particular attention in male patients aged ≤45 years. The FPE-incorporated nomogram showed excellent predictive performance for 3-, 5-, and 8-year end-stage renal disease (ESRD) risks(C-index=0.93; AUCs=0.958, 0.964, 0.892) and was well-calibrated. Furthermore, we found that FPE severity is an important factor influencing the treatment response, and immunosuppressive therapy (IST) can overcome this influence. For patients with severe FPE, IST is an essential intervention measure, and the recommended treatment duration is no less than 12 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFPE serves as an independent predictor of renal progression in patients with IgAN and holds significant clinical value.\u003c/p\u003e","manuscriptTitle":"The Significance of Foot Process Effacement in Renal Prognosis and Response to Treatment in IgA Nephropathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-10 16:17:59","doi":"10.21203/rs.3.rs-8938552/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":"3c8a5549-962b-4b23-b40c-3d6ed672d213","owner":[],"postedDate":"March 10th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-18T15:10:54+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-10 16:17:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8938552","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8938552","identity":"rs-8938552","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}