Repeat kidney Biopsy in 19 Children with IgA Vasculitis Nephritis: A Clinicopathological Analysis

Repeat kidney Biopsy in 19 Children with IgA Vasculitis Nephritis: A Clinicopathological Analysis | 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 Repeat kidney Biopsy in 19 Children with IgA Vasculitis Nephritis: A Clinicopathological Analysis Chenxi Ma, Jiuyu Liu, Xiang Fang, Pei Zhang, Zhengkun Xia, Chunlin Gao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7899626/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Immunoglobulin A vasculitis nephritis (IgAVN) is a common childhood vasculitis with heterogeneous clinical and pathological manifestations. Repeat kidney biopsy may help assess pathological evolution and guide treatment, but its role in pediatric IgAVN remains underexplored. This study aimed to evaluate the clinicopathological changes between initial and repeat biopsies and their association with treatment response and outcomes in children with IgAVN. Methods This single-center retrospective analysis included 19 pediatric IgAVN patients who underwent two kidney biopsies. Clinical, laboratory, and pathological data were compared between biopsies. Pathological evaluation used ISKDC, semiquantitative classification (SQC), and Oxford Classification (MEST-C) systems. Correlations between changes in proteinuria (Δ24hUP), eGFR slope, and pathological scores (ΔSQC, ΔActivity Index, ΔChronicity Index) were analyzed. Outcomes were classified as good (A/B) or poor (C/D) based on modified Counahan criteria. Results A total of 19 pediatric patients with IgAVN were included in this study. The cohort consisted of 12 males (63.2%) and 7 females (36.8%), with a mean age at disease onset of 10.6 ± 3.6 years. The median time from symptom onset to initial kidney biopsy was 155 days (IQR: 36, 364). A repeat kidney biopsy was performed at a median interval of 38 months (IQR: 18, 51) after the first biopsy, with the primary indications being disease recurrence (52.6%) and suboptimal treatment response (47.4%). Recurrent palpable purpura was observed in 31.6% of the patients at the time of repeat biopsy. Prior to the initial biopsy, 47.4% of the patients had received glucocorticoid therapy. The median follow-up duration for the entire cohort was 57 months (IQR: 38, 81). Microscopic hematuria improved significantly at the second biopsy ( p = 0.012), while 24-hour proteinuria did not change significantly. Pathological scores (SQC, MEST-C) also showed no significant change. A strong positive correlation was found between Δ24hUP and ΔActivity Index (r = 0.718, p < 0.001). 10 patients had good outcomes and 9 had poor outcomes, but no baseline or evolution parameters significantly predicted outcome. Treatment intensity increased after repeat biopsy, with more patients receiving pulse steroids and immunosuppressants. Conclusions Repeat kidney biopsy in pediatric IgAVN reveals discordance between clinical and pathological changes and supports its utility in guiding therapy adjustments. Proteinuria change strongly correlates with active pathological lesions, reinforcing its role in monitoring disease activity. IgA vasculitis nephritis Repeat kidney biopsy Children Pathological activity Outcome Figures Figure 1 Figure 2 Introduction Immunoglobulin A vasculitis nephritis (IgAV) represents one of the most common vasculitis in childhood[ 1 ],renl involvement severity dictates the disease outcome[ 2 ].Immunoglobulin A vasculitis nephritis (IAVN)is highly heterogeneous. Kidney biopsy with histological examination serves as the gold standard for both confirming the diagnosis and assessing the nature of kidney involvement. The International Pediatric Nephrology Association (IPNA) recommends kidney biopsy for children with IgA vasculitis (IgAV) who present with persistent proteinuria, nephrotic-range proteinuria, and/or reduced estimated glomerular filtration rate (eGFR)[ 3 ].While IgAVN was historically considered a benign condition with a favorable prognosis, emerging evidence indicates that a subset of pediatric patients experience kidney relapse[ 4 ]. Notably, approximately 1%–7% of children with IgAVN may progress to kidney failure or end-stage kidney disease (ESRD)[ 5 ]. A significant clinical challenge is the potential discrepancy between clinical manifestations and the actual underlying kidney pathological changes during the disease course or following therapeutic interventions. Performing a repeat kidney biopsy facilitates dynamic assessment of pathological evolution and helps differentiate the proportion of active inflammatory lesions from chronic fibrotic changes[ 6 ]. This information is critical for guiding adjustments to treatment strategies. However, current evidence regarding the optimal timing, indications, and the association of repeat kidney biopsy with long-term outcomes in pediatric IgAVN remains limited. To address this knowledge gap, this study conducted a retrospective clinicopathological analysis of 19 pediatric IgAVN patients who underwent two kidney biopsies. Our objectives were to compare the differences in clinical features, laboratory parameters, and pathological findings between the two biopsy time points, and to evaluate the utility of repeat kidney biopsy in assessing treatment response and predicting clinical outcomes. We anticipate that the findings will provide valuable insights for the individualized management and prognostic evaluation of children with IgAVN. Methods Patients Data for 19 children who had a clinical diagnosis of IgAVN and underwent two kidney biopsies between January 2010 to December 2024 at the Eastern Theater Command General Hospital, Pediatrics Department, were retrieved and analysed retrospectively from the onset of IgAVN until the latest follow-up visit. All of the children's parents provided informed consent for both kidney biopsies.Inclusion criteria were as follows: (1) presence of skin purpura with hematuria, proteinuria, hypertension, and/or reduced kidney function; (2) age under 18 years at the time of the initial kidney biopsy; (3) having undergone two kidney biopsies. Exclusion criteria included: (1) other secondary kidney diseases; (2) incomplete clinical data,follow-up duration < 1 year; (3) fewer than 8 glomeruli per kidney biopsy specimen. A total of 19 pediatric patients were enrolled in the study.Remission of IgAVN: resolution of proteinur ia (UPCR < 0.2 mg/mg or 20 mg/mmol or proteinuria < 100 mg/m 2 per day or < 0.2 g/day in 24-h collection) based on at least two urine samples collected at least 1 month apart in the presence of normal (≥ 90 mL/min/1.73 m 2 ) or stable eGFR. Complete remission includes, in addition to these features, the resolution of hematuria, defined as a negative dipstick for blood and/ or < 5 RBC/high-power microscopic field. Relapse of IgAVN: recurrence of hematuria (gross hematuria or ≥ 1 + in dipstick or 5 RBC/ high-power microscopic field) and/or proteinuria (UPCR ≥ 0.2 mg/mg or 20 mg/mmol) in at least two urine samples and/or reduced kidney function (eGFR 25% reduction from baseline) in a patient who has achieved a complete remission for at least 1 month[ 3 ]. Pathological evaluation of kidney biopsies was conducted in accordance with the International Study of Kidney Diseases in Children (ISKDC)[ 7 ]、semiquantitative classification(SQC)[ 8 ]and the Oxford Classification[ 9 ]. Clinical data and protocol All demographic, clinical, and laboratory data were collected at the time of each kidney biopsy. Demographic and clinical data, including age at biopsy, sex, medical history, systolic and diastolic blood pressure, duration of follow-up, and primary treatment regimens, were obtained from medical records. Hypertension was defined as blood pressure above the 95th percentile for age and sex. Urine and blood samples were collected at the time of biopsy for routine measurements, including levels of albumin (Alb), serum creatinine (Scr), uric acid (UA), immunoglobulins (IgA, IgG, and IgE), complement components (C3 and C4), 24 hour urinary protein (24hUP)and estimated glomerular filtration rate (eGFR). The eGFR was calculated using the bedside Schwartz formula[ 10 ]. When applying the Oxford Classification, we assigned a score of 1 for the presence of M1, E1, S1, T1, C1, and a score of 2 for T2 or C2 lesions; all other categories were assigned 0 points. The scores were then summed to generate a total score. The difference between the two SQC scores was defined as ΔSQC. Corresponding changes in acute and chronic lesion scores were defined as ΔActivity Index and ΔChronicity Index, respectively.The difference in 24-hour urinary protein excretion (24hUP) between the two biopsy time points was calculated as Δ24hUP. The ratio of estimated glomerular filtration rate (eGFR) values was expressed as the eGFR slope. For immunofluorescence analysis of kidney biopsies, the deposition intensity of IgA, IgM, and C3 in the mesangial area was semi-quantitatively scored based on fluorescence intensity as follows: negative (–) = 0, trace = 0.5, 1 + = 1, 2 + = 2, 3 + = 3, 4 + = 4. Outcome The clinical outcome was graded according to the modified classification of Counahan[ 7 ] as follows: A = Normal: the patient was normal on physical examination, with normal urine and kidney function; B = Minor urinary abnormality: the patient was normal on physical examination, with microscopic hematuria or proteinuria; C = Active kidney disease: the patient had proteinuria > 1 g/24 h or hypertension, or both, and a GFR > 60 mL/min/1.73 m 2 , D = Kidney insufficiency: the patient had a GFR < 60 mL/min/1.73 m 2 or had died. Outcome grades A and B represented good outcomes, and C and D represented poor outcomes. We performed the paired T-tests/Wilcoxon matched pair test to compare variables between the two kidney biopsies. We used the Mann–Whitney test for comparisons between two groups. For categorical variables, the χ2 test was used. Correlations were calculated using Spearman’s rank correlation. Statistical significance was set at the level of p < 0.05. Statistical evaluation was performed by statistical software, SPSS 27. Statistical visualization was performed using the R 4.4.2. Results Patient characteristics The study enrolled 19 pediatric patients, comprising 12 males (63.2%) and 7 females (36.8%). The mean age at disease onset was 10.6 ± 3.6 years. The median time from clinical manifestation to initial kidney biopsy was 155 days (IQR: 36, 364 days), and the median interval between the two kidney biopsies was 38 months (IQR: 18, 51 months). The median follow-up duration was 57 months (IQR: 38, 81 months).The indications for repeat kidney biopsy were as follows: disease recurrence of IgAVN in 10 cases (52.6%) and suboptimal response to treatment in 9 cases (47.4%). Among the patients who underwent repeat biopsy, 6 (31.6%) presented with recurrent palpable purpura. Prior to the first kidney biopsy, 9 patients (47.4%) had received glucocorticoid therapy. Comparative analysis of clinical, laboratory, and histopathological characteristics at the time of the first and second kidney biopsies is summarized in Table 1 . A comparison of clinical symptoms at the time of the two kidney biopsies showed a reduction in extrakidney manifestations at the second biopsy, although this difference was not statistically significant (p = 0.077). Other clinical symptoms remained similar between the two time points. Laboratory findings revealed a significant improvement in microscopic hematuria at the second biopsy(P = 0.012). The 24-hour urinary protein excretion also showed a reduction (from 1.1 to 0.8 g), although this change was not statistically significant. The notable increase in serum creatinine levels may be attributable to age-related physiological growth and development over time. Importantly, the remained stable, indicating preserved kidney function throughout the observation period. Pathological evaluation based on the Oxford Classification 、SQC and immunofluorescence deposition scores for IgA, IgM, and C3 showed no significant changes between twice biopsies. At the time of both kidney biopsies, the majority of the patienrs presented with the hematuria and proteinuria clinical type(68.4% vs. 78.9%). By the time of the second biopsy, two cases had progressed to the chronic nephritis syndrome type(Fig. 1 ). Patients’ Treatment Evolution and Outcomes The detailed information on kidney pathological changes, treatmentevolution, and outcomes of the 19 pediatric cases is presented in Table 2. Treatment Following the initial kidney biopsy, 13 patients (68.4%) received RASi therapy. All patients were treated with Prednisone. Methylprednisolone pulse therapy was administered to 8 patients (42.1%), with 1 to 3 courses delivered based on disease severity. One patient (5.3%) received cyclophosphamide pulse therapy. Mycophenolate mofetil was added in 7 cases (36.8%), while 3 patients (15.8%) received a combination of Mycophenolate mofetil and tacrolimus. Additionally, mizoribine (MZR) and leflunomide (LEF) were each administered to 3 patients (15.8%).After the repeat kidney biopsy, 16 patients (84.2%) continued corticosteroid therapy, and 16 (84.2%) remained on RASi. An SGLT2 inhibitor was incorporated into the treatment regimen for 8 patients (42.1%). Methylprednisolone pulse therapy was administered to 9 patients (47.4%). Immunosuppressive therapy included MMF in 10 patients (52.6%) and Tac in 10 patients (52.6%), with 5 patients (26.3%) receiving combination MMF and Tac. Leflunomide and mizoribine were used in 1 (5.3%) and 2 (10.5%) patients, respectively. Correlation between Pathological Changes and Clinical Parameters Spearman correlation analysis was conducted to evaluate the associations between changes in 24-hour urinary protein excretion (Δ24hUP), the eGFR slope, alterations in Oxford Classification scores, and changes in the semi-quantitative classification (ΔSQC) scores—including its acute (ΔActivity Index) and chronic (ΔChronicity Index) components. The analysis revealed a statistically significant positive correlation between the change in 24-hour urinary protein and the change in the total SQC score (r = 0.457, p = 0.049). Furthermore, a more pronounced positive correlation was observed between the change in proteinuria and the change in the acute component of the SQC score (r = 0.718, p < 0.001). No other significant correlations were detected among the remaining parameters (Fig. 2 ). Comparison of Clinical and Pathological Characteristics Between Prognostic Groups The baseline clinical and pathological characteristics of patients stratified by outcome are summarized in Table 3. Patients were categorized into two groups: those with favorable outcomes (Group A + B, n = 10) and those with unfavorable outcomes (Group C + D, n = 9). No statistically significant differences were observed in age, sex distribution, mean arterial pressure (MAP), time from symptom onset to first biopsy, or inter-biopsy interval between the two groups ( p > 0.05). Laboratory parameters, including levels of hematuria, 24-hour urinary protein excretion (24hUP), hemoglobin, serum albumin, serum creatinine, uric acid, lipid profiles, immunoglobulins (IgG, IgA, IgE), complement components (C3, C4), and baseline eGFR, also showed no significant differences between the groups ( p > 0.05). Furthermore, changes in pathological scores—including the ΔMEST-C, ΔSQC, Δ24hUP, and eGFR slope—did not differ significantly between the favorable and unfavorable outcome groups ( p > 0.05). Discussion This retrospective study analyzed the clinical and pathological data of 19 pediatric patients with IgAVN)who underwent repeat kidney biopsies. No procedure-related complications occurred after either biopsy. Older age at onset, heavy proteinuria, and severe clinical and pathological classifications were associated with unfavorable outcomes and difficulty achieving remission. At baseline, the mean urinary protein was 1.1 g/day, and 6 patients were classified as ISKDC grade II, with the remainder being grade III or higher. By the time of the second biopsy, microscopic hematuria had significantly improved, while 24-hour urinary protein quantification showed no significant change. Analysis of the paired biopsies revealed that the ISKDC grade improved in 3 patients but remained stable or worsened in 16. No statistically significant differences were observed in the SQC or MEST-C scores. After a mean follow-up of 57 months, 10 patients had favorable outcomes, while 9 had unfavorable outcomes. However, no statistically significant differences in baseline clinical characteristics, laboratory parameters, or pathological evolution indicators were identified between the outcome groups. Repeat kidney biopsy is most frequently used for assessing Lupus Nephritis (LN) and guiding treatment adjustments[ 11 , 12 ]. The optimal timing for repeat biopsy in IgAVN remains unclear. The IPNA suggests considering a repeat biopsy in cases of proteinuria relapse ± an unexplained decline in eGFR, or when proteinuria persists despite treatment.A Finland study[ 13 ] involving serial biopsies in patients with Henoch-Schönlein Nephritis (HSN), grouped by proteinuria presence at follow-up, found that the information from follow-up biopsies had limited prognostic impact. Conversely, other studies indicate that repeat biopsies can aid in prognosis prediction; for instance, static and dynamic assessments based on the Oxford classification from repeat biopsies improved the prediction of ESRD in IgA Nephropathy (IgAN) patients[ 14 ]. Proteinuria is a common clinical marker for assessing active kidney injury. Persistent proteinuria is associated with poor long-term outcomes [ 15 ],and its level correlates with the time to achieve remission[ 16 ].Wang et al[ 17 ] using a modified SQC scoring system in pediatric IgAVN,found that SQC activity and chronicity indices positively correlated with clinical manifestations,conventional pathological grading, and 24-hour urinary protein. In our cohort, the baseline mean urinary protein was 1.1 g/day. We similarly observed a strong correlation between the change in proteinuria (Δ24hUP) and the change in the pathological activity index (ΔActivity Index) (r = 0.718, p < 0.001). This correlation was stronger than that with the change in the total SQC score (r = 0.457, p = 0.049). This suggests that persistent or relapsing proteinuria should raise strong suspicion of underlying active pathological injury requiring intervention. Research by Shen et al[ 18 ] demonstrated that glomerular active lesions in IgAVN can be reversed with immunosuppressive therapy, MMF and tacrolimus have been shown to increase remission rates in refractory IgAVN[ 16 , 19 , 20 ].As shown in Table 2, treatment regimens were adjusted for most patients after the second biopsy: more received methylprednisolone pulse therapy (increasing from 42.1% to 47.4%), and the use of immunosuppressants like MMF and tacrolimus also increased. Some patients received multiple immunosuppressant adjustments/combinations following both initial and repeat biopsies, and 42.1% of patients newly received SGLT2 inhibitor therapy. For IgA nephropathy patients with severe kidney lesions who are undergoing immunosuppressive therapy, SGLT2 inhibitor can further reduce proteinuria and lower the risk of chronic kidney disease progression[ 21 , 22 ]. However, randomized controlled trials in the pediatric population are still needed to confirm its efficacy[ 23 ]. Despite this intensified immunosuppressive treatment, nearly half of the patients had an unfavorable outcome at the last follow-up. Two Chinese studies on refractory IgAVN/IgAN in children using Telitacicept (a dual B-cell pathway inhibitor) [ 24 , 25 ] reported that the vast majority of children achieved proteinuria remission, with reduced glucocorticoid usage and a favorable safety profile. Although the sample sizes were small, these results suggest that Telitacicept is a promising option for refractory IgAVN. Our center is also exploring the use of Telitacicept for refractory IgAVN, though results are not yet published. In this study, we failed to identify significant baseline or evolution parameters predictive of long-term clinical outcomes. Several factors may explain this: First, this was a single-center, retrospective study with a small sample size (n = 19), limiting statistical power to detect subtle but clinically relevant differences. Second, all enrolled patients received aggressive and individualized immunosuppressive therapy, which may have altered the natural disease course and obscured the predictive value of certain potential prognostic factors. Furthermore, the long-term prognosis of pediatric IgAVN is likely influenced by multiple factors over an extended period, and our median follow-up of 57 months might be insufficient to fully capture ultimate kidney outcome disparities. The lack of uniform indications for repeat biopsy and standardized treatment protocols may have introduced selection and confounding biases. In conclusion, this analysis of repeat kidney biopsies in 19 pediatric IgAVN patients confirms that clinical indicators and pathological changes can be discordant. It underscores the indispensable role of repeat biopsy in precise disease assessment and guiding treatment strategy adjustments. We have, for the first time in this population, established a strong correlation between changes in proteinuria and the evolution of kidney active lesions, supporting the use of proteinuria as a core clinical marker for monitoring disease activity. Future research should focus on exploring more sensitive non-invasive biomarkers (e.g., urinary biomarkers, serum levels of galactose-deficient IgA1) to potentially supplement or partially replace invasive kidney biopsies. Declarations Ethics approval and consent to participate The study has been ethically reviewed and approved by the Ethics Committee of Jinling Clinical Medical College，Nanjing Medical University, as indicated by the approval number (2024DZKY-105-01). In line with ethical standards, informed consent has been secured from the guardians of the participating children. Competing interests The authors declare no competing interests. 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Kidney Int Rep 10:940–943. https://doi.org/10.1016/j.ekir.2024.11.1363 Tables Table 1 Clinical, laboratory and Pathological characteristics at first and second biopsies First biopsy (n=19) Second biopsy (n=19) p Clinical features Prodromal infection 2 (10.5%) 6 (31.6%) 0.289 Gross hematuria 4(21.1%) 2 (10.5%) 0.603 Extrakidney manifestations 7（36.8%） 1（5.3%） 0.077 Body mass index (kg/m 2 ) 19.9±4.3 21.1±5.8 0.301 MAP (mmHg) 84.0（82.3,90.0） 86.7（82.7,90.7） 0.872 Laboratory features Hematuria(/μL) 207.7（72.9,613.2） 35.4（25.8,154.8） 0.012* 24hUP (g/24 h) 1.1（0.2,1,7） 0.8（0.6,1.9） 0.777 ALB(g/L) 39.8±4.7 38.3±5.9 0.301 UA(μmol/L) 320.0（297.5,380） 319.0（300.0,391.5） 0.862 Total cholesterol (mmol/l) 4.5（4.0,5.6） 4.3（3.8,4.9） 0.469 Scr(μmol/L) 43.2（38.5,54.3） 58.8（42.7,67.8） 0.002* Hb（g/L） 139.6±11.7 137.9±18.0 0.619 Triglyceride (mmol/l) 1.6±0.7 1.4±0.5 0.190 eGFR(mL/min/1.73 m 2 ) 172.0±41.3 162.3±48.2 0.465 Pathologial features M1,n% （31.6%） （47.4%） 0.371 E1,n% （31.6%） （36.8%） 1.000 S1,n% （31.6%） (52.6%) 0.343 T1/T2,n% （0.0%） （5.3%） 1.000 C1,n% （36.8%） （42.1%） 1.000 C2,n% （15.8%） 0（0.0%） 0.230 IgA 2（2,2） 2（2,3） 0.340 IgM 1（0,1） 1（0.5,1） 0.330 C3 2（1,2） 1（1,2） 0.469 MEST-C 1.6±1.5 1.8±1.3 0.586 SQC 4.6±2.5 5.2±2.8 0.406 * p ＜0.05；Abbreviations: 24hUP, 24h urinary protein;eGFR, estimated glomerular filtration rate; Ig, immunoglobulin;; Scr, serum creatinine; UA, uric acid；MAP mean arterial pressure;Hb,Hemoglobin；ALB,Serum Albumin；C3, alexin 3; C4, alexin 4；SQC,the modified semiquantitative classification；MAP = Diastolic Blood Pressure + 1/3 × (Systolic Blood Pressure - Diastolic Blood Pressure)；Extrakidney symptoms include abdominal pain and joint pain associated with IgAVN. Table20. Patients’ characteristics、treatment evolution and outcomes No. Sex Age （ years ） Time to first biopsy (days) Inter-biopsy interval (mo) Evolution of the ISKDC scores Evolution of the MEST-C scores Initial treatment Treatment after repeat biopsy Outcome 1 M 8.1 27 18 Ⅲa→Ⅲa M1E1S1T0-C2→M1E1S1T0-C0 RASi+PDN+MPPT*1+MMF+TAC RASi+SGLT2i+PDN+TAC C 2 M 6.9 189 113 Ⅲb→Ⅲa M1E1S1T0-C0→M1E0S0T0-C0 RASi+PDN+TwHF+MMF RASi+PDN+MMF+TAC A 3 M 9.4 23 32 Ⅳ→Ⅲb M0E1S0T0-C2→M1E1S1T1-C1 RASi+PDN+MPPT*3+MMF+TAC RASi+PDN+MPPT*1+TAC C 4 M 10.3 379 39 Ⅲa→Ⅲa M1E1S1T0-C1→M1E0S0T0-C0 RASi+PDN+MPPT*1+MMF+TAC RASi+PDN+TAC C 5 F 5.0 596 46 Ⅲa→Ⅱa M0E0S0T0-C0→M0E0S0T0-C0 RASi+PDN RASi+PDN+MPPT*1+TAC B 6 M 4.3 380 21 Ⅱa→Ⅲa M0E0S0T0-C0→M0E1S0TO-C1 PDN RASi+PDN+MPPT*2+MMF+TAC B 7 M 10.8 45 8 Ⅲa→Ⅲa M0E0S0T0-C2→M1E0S0T0-C1 RASi+PDN+MPPT*3 RASi+PDN+MMF+TAC A 8 M 14.9 236 22 Ⅱa→Ⅲa M1E0S0T0-C0→M0E0S1T0-C1 RASi+PDN RASi+SGLT2i+PDN+MMF D 9 F 17.8 9 79 Ⅲa→Ⅲa M1E0S1T0-C0→M1E0S1T0-C0 RASi+PDN+TwHF+LEF RASi+SGLT2i+LEF D 10 M 9.1 19 51 Ⅲa→Ⅲa M0E0S0T0-C1→M0E0S0T0-C1 PDN+MPPT*2+CTX*3+MMF PDN+MPPT*1+MMF C 11 F 14.3 64 10 Ⅱa→Ⅲa M0E0S0T0-C0→M0E0S1T0-C1 PDN+MPPT*1 PDN+MPPT*1+MMF+TAC+MZR B 12 M 9.8 50 40 Ⅱa→Ⅲa M0E0S0T0-C0→M1E0S1T0-C0 RASi+PDN RASi+SGLT2i+PDN+MMF C 13 M 15.6 155 18 Ⅲa→Ⅲa M0E0S1TO-C1→M0E0S0T0-C0 RASi+PDN+LEF+MZR RASi+PDN+TAC B 14 F 9.5 18 51 Ⅲa→Ⅲa M0E1S0T0-C1→M0E1S1T0-C0 RASi+PDN+MPPT*3+MMF RASi+SGLT2i+MPPT*1+MMF B 15 F 13.9 350 17 Ⅱb→Ⅲb M1E0S0T0-C0→M1E1S1T0-C1 RASi+PDN+MZR RASi+PDN+MPPT*1 C 16 F 13.1 378 38 Ⅲa→Ⅲa M0E0S0T0-C1→M0E1S1T0-C0 PDN+MMF RASi+PDN+SGLT2i+MPPT*1+MMF+TAC A 17 F 11.0 192 21 Ⅲa→Ⅱa M0E0S0T0-C1→M0E0S0T0-C0 RASi+PDN+LEF RASi+MZR B 18 M 9.8 88 102 Ⅱa→Ⅲa M0E0S0T0-C0→M1E0S1T0-C0 PDN RASi+SGLT2i C 19 M 7.3 414 45 Ⅲa→Ⅲa M0E1S1T0-C1→M0E0S1T0-C1 RASi+PDN+MPPT*1 RASi+SGLT2i+MPPT*2+MMF A M male ;F female; RASi renin angiotensin system inhibitor, PDN Prednisone. TwHF Tripterygium glycosides, MPPT Methylprednisolone PulseTherapy, TAC Tacrolimus, MMF Mycophenolate Mofetil, SGLT2i Sodium-Glucose Cotransporter-2 Inhibitor , LEF Leflunomide, CTX Cyclophosphamide, MZR Mizoribine Table 3 Clinical and Pathological Features by outcomes Group A+B （ n=10 ） Group C+D （ n=9 ） p Age（years） 9.8±3.9 11.5±3.3 0.318 Sex F（50%） F（22.2%） 0.350 MAP（mmHg） 86.7（83.3,89.8） 82.3（80.0,86.7） 0.084 Time to first biopsy (days) 19.2±4.6 84.9±13.4 0.156 Inter-biopsy interval (mo) 86.7（83.3,89.8） 82.3（80.0,86.7） 0.540 Hematuria(/μL) 127.75（66.9,490.4） 232.0（192.6,726.8） 0.447 24hUP (g/24 h) 0.5（0.2,1.1） 1.3（1.1,2.0） 0.307 Hb（g/L） 139.5±15.1 139.7±7.2 0.976 ALB(g/L) 40.2±4.0 39.3±5.6 0.706 Scr(μmol/L) 42.2±11.3 49.6±11.8 0.179 UA(μmol/L) 307.4±65.3 364.4±91.2 0.142 Total cholesterol (mmol/l) 4.5±1.0 5.2±1.3 0.226 Triglyceride (mmol/l) 1.6±0.5 1.7±0.9 0.780 IgG 7.9（6.9,10.9） 8.2（6.6,10.5） 0.720 IgA 2.2±0.4 2.5±1.0 0.325 IgE 77.4（50.5,141.5） 85.6（42.8,197.0） 0.842 C3 1.1±0.2 1.2±0.3 0.333 C4 0.2±0.1 0.3±0.1 0.241 eGFR 174.6±33.4 169.3±50.7 0.795 ΔMEST-C 190.5（86.8,379.5） 50（23.0,51.0） 0.244 ΔSQC 29.5（18.8,45.5） 39.0（22.0,51.0） 0.400 Δ24hUP 0.0±2.3 1.2±3.6 0.604 eGRF Slope 4.1±2.1 5.2±3.0 0.720 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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1","display":"","copyAsset":false,"role":"figure","size":101721,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of clinical types at the two kidney biopsies\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7899626/v1/760c456c196bfa4fa5d267da.png"},{"id":96249721,"identity":"abf43c48-4de1-4538-ad77-0e78fc8ce1c4","added_by":"auto","created_at":"2025-11-19 07:36:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":149135,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between the Evolution of Pathological and Clinical Indicators\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7899626/v1/c9618a0a4525d45db55ec82f.png"},{"id":97148845,"identity":"d3970a1b-3a32-4354-ad7b-ca9ea5f2d366","added_by":"auto","created_at":"2025-12-01 10:19:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1050024,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7899626/v1/523afeaa-766d-4b27-8d86-156dd08b1188.pdf"}],"financialInterests":"","formattedTitle":"Repeat kidney Biopsy in 19 Children with IgA Vasculitis Nephritis: A Clinicopathological Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eImmunoglobulin A vasculitis nephritis (IgAV) represents one of the most common vasculitis in childhood[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e],renl involvement severity dictates the disease outcome[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].Immunoglobulin A vasculitis nephritis (IAVN)is highly heterogeneous. Kidney biopsy with histological examination serves as the gold standard for both confirming the diagnosis and assessing the nature of kidney involvement. The International Pediatric Nephrology Association (IPNA) recommends kidney biopsy for children with IgA vasculitis (IgAV) who present with persistent proteinuria, nephrotic-range proteinuria, and/or reduced estimated glomerular filtration rate (eGFR)[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].While IgAVN was historically considered a benign condition with a favorable prognosis, emerging evidence indicates that a subset of pediatric patients experience kidney relapse[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Notably, approximately 1%\u0026ndash;7% of children with IgAVN may progress to kidney failure or end-stage kidney disease (ESRD)[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. A significant clinical challenge is the potential discrepancy between clinical manifestations and the actual underlying kidney pathological changes during the disease course or following therapeutic interventions.\u003c/p\u003e\u003cp\u003ePerforming a repeat kidney biopsy facilitates dynamic assessment of pathological evolution and helps differentiate the proportion of active inflammatory lesions from chronic fibrotic changes[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This information is critical for guiding adjustments to treatment strategies. However, current evidence regarding the optimal timing, indications, and the association of repeat kidney biopsy with long-term outcomes in pediatric IgAVN remains limited.\u003c/p\u003e\u003cp\u003eTo address this knowledge gap, this study conducted a retrospective clinicopathological analysis of 19 pediatric IgAVN patients who underwent two kidney biopsies. Our objectives were to compare the differences in clinical features, laboratory parameters, and pathological findings between the two biopsy time points, and to evaluate the utility of repeat kidney biopsy in assessing treatment response and predicting clinical outcomes. We anticipate that the findings will provide valuable insights for the individualized management and prognostic evaluation of children with IgAVN.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients\u003c/h2\u003e\u003cp\u003eData for 19 children who had a clinical diagnosis of IgAVN and underwent two kidney biopsies between January 2010 to December 2024 at the Eastern Theater Command General Hospital, Pediatrics Department, were retrieved and analysed retrospectively from the onset of IgAVN until the latest follow-up visit. All of the children's parents provided informed consent for both kidney biopsies.Inclusion criteria were as follows: (1) presence of skin purpura with hematuria, proteinuria, hypertension, and/or reduced kidney function; (2) age under 18 years at the time of the initial kidney biopsy; (3) having undergone two kidney biopsies. Exclusion criteria included: (1) other secondary kidney diseases; (2) incomplete clinical data,follow-up duration\u0026thinsp;\u0026lt;\u0026thinsp;1 year; (3) fewer than 8 glomeruli per kidney biopsy specimen. A total of 19 pediatric patients were enrolled in the study.Remission of IgAVN: resolution of proteinur ia (UPCR\u0026thinsp;\u0026lt;\u0026thinsp;0.2 mg/mg or 20 mg/mmol or proteinuria\u0026thinsp;\u0026lt;\u0026thinsp;100 mg/m\u003csup\u003e2\u003c/sup\u003e per day or \u0026lt;\u0026thinsp;0.2 g/day in 24-h collection) based on at least two urine samples collected at least 1 month apart in the presence of normal (\u0026ge;\u0026thinsp;90 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e) or stable eGFR. Complete remission includes, in addition to these features, the resolution of hematuria, defined as a negative dipstick for blood and/ or \u0026lt;\u0026thinsp;5 RBC/high-power microscopic field. Relapse of IgAVN: recurrence of hematuria (gross hematuria or \u0026ge;\u0026thinsp;1\u0026thinsp;+\u0026thinsp;in dipstick or 5 RBC/ high-power microscopic field) and/or proteinuria (UPCR\u0026thinsp;\u0026ge;\u0026thinsp;0.2 mg/mg or 20 mg/mmol) in at least two urine samples and/or reduced kidney function (eGFR\u0026thinsp;\u0026lt;\u0026thinsp;90 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e or \u0026gt;\u0026thinsp;25% reduction from baseline) in a patient who has achieved a complete remission for at least 1 month[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Pathological evaluation of kidney biopsies was conducted in accordance with the International Study of Kidney Diseases in Children (ISKDC)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]、semiquantitative classification(SQC)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]and the Oxford Classification[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eClinical data and protocol\u003c/h3\u003e\n\u003cp\u003eAll demographic, clinical, and laboratory data were collected at the time of each kidney biopsy. Demographic and clinical data, including age at biopsy, sex, medical history, systolic and diastolic blood pressure, duration of follow-up, and primary treatment regimens, were obtained from medical records. Hypertension was defined as blood pressure above the 95th percentile for age and sex. Urine and blood samples were collected at the time of biopsy for routine measurements, including levels of albumin (Alb), serum creatinine (Scr), uric acid (UA), immunoglobulins (IgA, IgG, and IgE), complement components (C3 and C4), 24 hour urinary protein (24hUP)and estimated glomerular filtration rate (eGFR). The eGFR was calculated using the bedside Schwartz formula[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. When applying the Oxford Classification, we assigned a score of 1 for the presence of M1, E1, S1, T1, C1, and a score of 2 for T2 or C2 lesions; all other categories were assigned 0 points. The scores were then summed to generate a total score. The difference between the two SQC scores was defined as ΔSQC. Corresponding changes in acute and chronic lesion scores were defined as ΔActivity Index and ΔChronicity Index, respectively.The difference in 24-hour urinary protein excretion (24hUP) between the two biopsy time points was calculated as Δ24hUP. The ratio of estimated glomerular filtration rate (eGFR) values was expressed as the eGFR slope. For immunofluorescence analysis of kidney biopsies, the deposition intensity of IgA, IgM, and C3 in the mesangial area was semi-quantitatively scored based on fluorescence intensity as follows: negative (\u0026ndash;)\u0026thinsp;=\u0026thinsp;0, trace\u0026thinsp;=\u0026thinsp;0.5, 1\u0026thinsp;+\u0026thinsp;=\u0026thinsp;1, 2\u0026thinsp;+\u0026thinsp;=\u0026thinsp;2, 3\u0026thinsp;+\u0026thinsp;=\u0026thinsp;3, 4\u0026thinsp;+\u0026thinsp;=\u0026thinsp;4.\u003c/p\u003e\n\u003ch3\u003eOutcome\u003c/h3\u003e\n\u003cp\u003eThe clinical outcome was graded according to the modified classification of Counahan[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] as follows: A\u0026thinsp;=\u0026thinsp;Normal: the patient was normal on physical examination, with normal urine and kidney function; B\u0026thinsp;=\u0026thinsp;Minor urinary abnormality: the patient was normal on physical examination, with microscopic hematuria or proteinuria; C\u0026thinsp;=\u0026thinsp;Active kidney disease: the patient had proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;1 g/24 h or hypertension, or both, and a GFR\u0026thinsp;\u0026gt;\u0026thinsp;60 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e, D\u0026thinsp;=\u0026thinsp;Kidney insufficiency: the patient had a GFR\u0026thinsp;\u0026lt;\u0026thinsp;60 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e or had died. Outcome grades A and B represented good outcomes, and C and D represented poor outcomes.\u003c/p\u003e\u003cp\u003eWe performed the paired T-tests/Wilcoxon matched pair test to compare variables between the two kidney biopsies. We used the Mann\u0026ndash;Whitney test for comparisons between two groups. For categorical variables, the χ2 test was used. Correlations were calculated using Spearman\u0026rsquo;s rank correlation. Statistical significance was set at the level of \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Statistical evaluation was performed by statistical software, SPSS 27. Statistical visualization was performed using the R 4.4.2.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient characteristics\u003c/h2\u003e\n \u003cp\u003eThe study enrolled 19 pediatric patients, comprising 12 males (63.2%) and 7 females (36.8%). The mean age at disease onset was 10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6 years. The median time from clinical manifestation to initial kidney biopsy was 155 days (IQR: 36, 364 days), and the median interval between the two kidney biopsies was 38 months (IQR: 18, 51 months). The median follow-up duration was 57 months (IQR: 38, 81 months).The indications for repeat kidney biopsy were as follows: disease recurrence of IgAVN in 10 cases (52.6%) and suboptimal response to treatment in 9 cases (47.4%). Among the patients who underwent repeat biopsy, 6 (31.6%) presented with recurrent palpable purpura. Prior to the first kidney biopsy, 9 patients (47.4%) had received glucocorticoid therapy.\u003c/p\u003e\n \u003cp\u003eComparative analysis of clinical, laboratory, and histopathological characteristics at the time of the first and second kidney biopsies is summarized in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. A comparison of clinical symptoms at the time of the two kidney biopsies showed a reduction in extrakidney manifestations at the second biopsy, although this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.077). Other clinical symptoms remained similar between the two time points. Laboratory findings revealed a significant improvement in microscopic hematuria at the second biopsy(P\u0026thinsp;=\u0026thinsp;0.012). The 24-hour urinary protein excretion also showed a reduction (from 1.1 to 0.8 g), although this change was not statistically significant. The notable increase in serum creatinine levels may be attributable to age-related physiological growth and development over time. Importantly, the remained stable, indicating preserved kidney function throughout the observation period. Pathological evaluation based on the Oxford Classification 、SQC and immunofluorescence deposition scores for IgA, IgM, and C3 showed no significant changes between twice biopsies.\u003c/p\u003e\n \u003cp\u003eAt the time of both kidney biopsies, the majority of the patienrs presented with the hematuria and proteinuria clinical type(68.4% vs. 78.9%). By the time of the second biopsy, two cases had progressed to the chronic nephritis syndrome type(Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003ePatients\u0026rsquo; Treatment Evolution and Outcomes\u003c/h2\u003e\n \u003cp\u003eThe detailed information on kidney pathological changes, treatmentevolution, and outcomes of the 19 pediatric cases is presented in Table\u0026nbsp;2.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eTreatment\u003c/h3\u003e\n\u003cp\u003eFollowing the initial kidney biopsy, 13 patients (68.4%) received RASi therapy. All patients were treated with Prednisone. Methylprednisolone pulse therapy was administered to 8 patients (42.1%), with 1 to 3 courses delivered based on disease severity. One patient (5.3%) received cyclophosphamide pulse therapy. Mycophenolate mofetil was added in 7 cases (36.8%), while 3 patients (15.8%) received a combination of Mycophenolate mofetil and tacrolimus. Additionally, mizoribine (MZR) and leflunomide (LEF) were each administered to 3 patients (15.8%).After the repeat kidney biopsy, 16 patients (84.2%) continued corticosteroid therapy, and 16 (84.2%) remained on RASi. An SGLT2 inhibitor was incorporated into the treatment regimen for 8 patients (42.1%). Methylprednisolone pulse therapy was administered to 9 patients (47.4%). Immunosuppressive therapy included MMF in 10 patients (52.6%) and Tac in 10 patients (52.6%), with 5 patients (26.3%) receiving combination MMF and Tac. Leflunomide and mizoribine were used in 1 (5.3%) and 2 (10.5%) patients, respectively.\u003c/p\u003e\n\u003ch3\u003eCorrelation between Pathological Changes and Clinical Parameters\u003c/h3\u003e\n\u003cp\u003eSpearman correlation analysis was conducted to evaluate the associations between changes in 24-hour urinary protein excretion (\u0026Delta;24hUP), the eGFR slope, alterations in Oxford Classification scores, and changes in the semi-quantitative classification (\u0026Delta;SQC) scores\u0026mdash;including its acute (\u0026Delta;Activity Index) and chronic (\u0026Delta;Chronicity Index) components.\u003c/p\u003e\n\u003cp\u003eThe analysis revealed a statistically significant positive correlation between the change in 24-hour urinary protein and the change in the total SQC score (r\u0026thinsp;=\u0026thinsp;0.457, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049). Furthermore, a more pronounced positive correlation was observed between the change in proteinuria and the change in the acute component of the SQC score (r\u0026thinsp;=\u0026thinsp;0.718, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No other significant correlations were detected among the remaining parameters (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eComparison of Clinical and Pathological Characteristics Between Prognostic Groups\u003c/h2\u003e\n \u003cp\u003eThe baseline clinical and pathological characteristics of patients stratified by outcome are summarized in Table\u0026nbsp;3. Patients were categorized into two groups: those with favorable outcomes (Group A\u0026thinsp;+\u0026thinsp;B, n\u0026thinsp;=\u0026thinsp;10) and those with unfavorable outcomes (Group C\u0026thinsp;+\u0026thinsp;D, n\u0026thinsp;=\u0026thinsp;9). No statistically significant differences were observed in age, sex distribution, mean arterial pressure (MAP), time from symptom onset to first biopsy, or inter-biopsy interval between the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n \u003cp\u003eLaboratory parameters, including levels of hematuria, 24-hour urinary protein excretion (24hUP), hemoglobin, serum albumin, serum creatinine, uric acid, lipid profiles, immunoglobulins (IgG, IgA, IgE), complement components (C3, C4), and baseline eGFR, also showed no significant differences between the groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n \u003cp\u003eFurthermore, changes in pathological scores\u0026mdash;including the \u0026Delta;MEST-C, \u0026Delta;SQC, \u0026Delta;24hUP, and eGFR slope\u0026mdash;did not differ significantly between the favorable and unfavorable outcome groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study analyzed the clinical and pathological data of 19 pediatric patients with IgAVN)who underwent repeat kidney biopsies. No procedure-related complications occurred after either biopsy. Older age at onset, heavy proteinuria, and severe clinical and pathological classifications were associated with unfavorable outcomes and difficulty achieving remission. At baseline, the mean urinary protein was 1.1 g/day, and 6 patients were classified as ISKDC grade II, with the remainder being grade III or higher. By the time of the second biopsy, microscopic hematuria had significantly improved, while 24-hour urinary protein quantification showed no significant change. Analysis of the paired biopsies revealed that the ISKDC grade improved in 3 patients but remained stable or worsened in 16. No statistically significant differences were observed in the SQC or MEST-C scores. After a mean follow-up of 57 months, 10 patients had favorable outcomes, while 9 had unfavorable outcomes. However, no statistically significant differences in baseline clinical characteristics, laboratory parameters, or pathological evolution indicators were identified between the outcome groups.\u003c/p\u003e\u003cp\u003eRepeat kidney biopsy is most frequently used for assessing Lupus Nephritis (LN) and guiding treatment adjustments[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The optimal timing for repeat biopsy in IgAVN remains unclear. The IPNA suggests considering a repeat biopsy in cases of proteinuria relapse\u0026thinsp;\u0026plusmn;\u0026thinsp;an unexplained decline in eGFR, or when proteinuria persists despite treatment.A Finland study[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] involving serial biopsies in patients with Henoch-Sch\u0026ouml;nlein Nephritis (HSN), grouped by proteinuria presence at follow-up, found that the information from follow-up biopsies had limited prognostic impact. Conversely, other studies indicate that repeat biopsies can aid in prognosis prediction; for instance, static and dynamic assessments based on the Oxford classification from repeat biopsies improved the prediction of ESRD in IgA Nephropathy (IgAN) patients[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eProteinuria is a common clinical marker for assessing active kidney injury. Persistent proteinuria is associated with poor long-term outcomes [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e],and its level correlates with the time to achieve remission[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].Wang et al[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] using a modified SQC scoring system in pediatric IgAVN,found that SQC activity and chronicity indices positively correlated with clinical manifestations,conventional pathological grading, and 24-hour urinary protein. In our cohort, the baseline mean urinary protein was 1.1 g/day. We similarly observed a strong correlation between the change in proteinuria (Δ24hUP) and the change in the pathological activity index (ΔActivity Index) (r\u0026thinsp;=\u0026thinsp;0.718, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This correlation was stronger than that with the change in the total SQC score (r\u0026thinsp;=\u0026thinsp;0.457, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049). This suggests that persistent or relapsing proteinuria should raise strong suspicion of underlying active pathological injury requiring intervention. Research by Shen et al[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] demonstrated that glomerular active lesions in IgAVN can be reversed with immunosuppressive therapy, MMF and tacrolimus have been shown to increase remission rates in refractory IgAVN[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].As shown in Table\u0026nbsp;2, treatment regimens were adjusted for most patients after the second biopsy: more received methylprednisolone pulse therapy (increasing from 42.1% to 47.4%), and the use of immunosuppressants like MMF and tacrolimus also increased. Some patients received multiple immunosuppressant adjustments/combinations following both initial and repeat biopsies, and 42.1% of patients newly received SGLT2 inhibitor therapy. For IgA nephropathy patients with severe kidney lesions who are undergoing immunosuppressive therapy, SGLT2 inhibitor can further reduce proteinuria and lower the risk of chronic kidney disease progression[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, randomized controlled trials in the pediatric population are still needed to confirm its efficacy[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Despite this intensified immunosuppressive treatment, nearly half of the patients had an unfavorable outcome at the last follow-up. Two Chinese studies on refractory IgAVN/IgAN in children using Telitacicept (a dual B-cell pathway inhibitor) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] reported that the vast majority of children achieved proteinuria remission, with reduced glucocorticoid usage and a favorable safety profile. Although the sample sizes were small, these results suggest that Telitacicept is a promising option for refractory IgAVN. Our center is also exploring the use of Telitacicept for refractory IgAVN, though results are not yet published.\u003c/p\u003e\u003cp\u003eIn this study, we failed to identify significant baseline or evolution parameters predictive of long-term clinical outcomes. Several factors may explain this: First, this was a single-center, retrospective study with a small sample size (n\u0026thinsp;=\u0026thinsp;19), limiting statistical power to detect subtle but clinically relevant differences. Second, all enrolled patients received aggressive and individualized immunosuppressive therapy, which may have altered the natural disease course and obscured the predictive value of certain potential prognostic factors. Furthermore, the long-term prognosis of pediatric IgAVN is likely influenced by multiple factors over an extended period, and our median follow-up of 57 months might be insufficient to fully capture ultimate kidney outcome disparities. The lack of uniform indications for repeat biopsy and standardized treatment protocols may have introduced selection and confounding biases. In conclusion, this analysis of repeat kidney biopsies in 19 pediatric IgAVN patients confirms that clinical indicators and pathological changes can be discordant. It underscores the indispensable role of repeat biopsy in precise disease assessment and guiding treatment strategy adjustments. We have, for the first time in this population, established a strong correlation between changes in proteinuria and the evolution of kidney active lesions, supporting the use of proteinuria as a core clinical marker for monitoring disease activity. Future research should focus on exploring more sensitive non-invasive biomarkers (e.g., urinary biomarkers, serum levels of galactose-deficient IgA1) to potentially supplement or partially replace invasive kidney biopsies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study has been ethically reviewed and approved by the Ethics Committee of Jinling Clinical Medical College，Nanjing Medical University, as indicated by the approval number (2024DZKY-105-01). In line with ethical standards, informed consent has been secured from the guardians of the participating children. \u0026nbsp;\u0026nbsp;\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\u003cli\u003e\u003cspan\u003eHetland L, Susrud K, Lindahl K, Bygum A (2017) Henoch-Sch\u0026ouml;nlein Purpura: A Literature Review. Acta Derm Venerol 97:1160\u0026ndash;1166. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2340/00015555-2733\u003c/span\u003e\u003cspan address=\"10.2340/00015555-2733\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThervet E, Pillebout E, Guillevin L, CESAR study group (2003) Outcome after childhood Henoch-Sch\u0026ouml;nlein purpura. 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Kidney Int Rep 10:940\u0026ndash;943. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ekir.2024.11.1363\u003c/span\u003e\u003cspan address=\"10.1016/j.ekir.2024.11.1363\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 Clinical, laboratory and Pathological characteristics at first and second biopsies\u0026nbsp;\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"571\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFirst biopsy (n=19)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecond biopsy (n=19)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical features\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eProdromal infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e2 (10.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e6 (31.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.289\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eGross hematuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e4(21.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e2 (10.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.603\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eExtrakidney manifestations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e7（36.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e1（5.3%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.077\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e19.9\u0026plusmn;4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e21.1\u0026plusmn;5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.301\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eMAP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e84.0（82.3,90.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e86.7（82.7,90.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.872\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaboratory\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003efeatures\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eHematuria(/\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e207.7（72.9,613.2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e35.4（25.8,154.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.012*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e24hUP (g/24 h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e1.1（0.2,1,7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e0.8（0.6,1.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.777\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eALB(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e39.8\u0026plusmn;4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e38.3\u0026plusmn;5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.301\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eUA(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e320.0（297.5,380）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e319.0（300.0,391.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.862\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eTotal cholesterol (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e4.5（4.0,5.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e4.3（3.8,4.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eScr(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e43.2（38.5,54.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e58.8（42.7,67.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eHb（g/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e139.6\u0026plusmn;11.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e137.9\u0026plusmn;18.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.619\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eTriglyceride (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e1.6\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e1.4\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.190\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eeGFR(mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e172.0\u0026plusmn;41.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e162.3\u0026plusmn;48.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.465\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathologial features\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eM1,n%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e（31.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e（47.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.371\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eE1,n%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e（31.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e（36.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eS1,n%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e（31.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e(52.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.343\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eT1/T2,n%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e（0.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e（5.3%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eC1,n%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e（36.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e（42.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eC2,n%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e（15.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e0（0.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eIgA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e2（2,2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e2（2,3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.340\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eIgM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e1（0,1）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e1（0.5,1）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.330\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eC3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e2（1,2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e1（1,2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eMEST-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e1.6\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e1.8\u0026plusmn;1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.586\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eSQC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e4.6\u0026plusmn;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003e5.2\u0026plusmn;2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.406\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*\u003cem\u003ep\u003c/em\u003e＜0.05；Abbreviations: 24hUP, 24h urinary protein;eGFR, estimated glomerular filtration rate; Ig, immunoglobulin;; Scr, serum creatinine; UA, uric acid；MAP mean arterial pressure;Hb,Hemoglobin；ALB,Serum Albumin；C3, alexin 3; C4, alexin 4；SQC,the modified semiquantitative classification；MAP = Diastolic Blood Pressure + 1/3 \u0026times; (Systolic Blood Pressure - Diastolic Blood Pressure)；Extrakidney symptoms include abdominal pain and joint pain associated with IgAVN.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable20.\u003c/strong\u003e Patients\u0026rsquo; characteristics、treatment evolution and outcomes\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003eyears\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime to first biopsy\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInter-biopsy interval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(mo)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvolution of the ISKDC scores\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvolution of the MEST-C scores\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInitial treatment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment after repeat biopsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e8.1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e18\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM1E1S1T0-C2\u0026rarr;M1E1S1T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+MPPT*1+MMF+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+SGLT2i+PDN+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e6.9\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e113\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢb\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM1E1S1T0-C0\u0026rarr;M1E0S0T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+TwHF+MMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+PDN+MMF+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e9.4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e32\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅣ\u0026rarr;Ⅲb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E1S0T0-C2\u0026rarr;M1E1S1T1-C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+MPPT*3+MMF+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+PDN+MPPT*1+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e10.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e39\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM1E1S1T0-C1\u0026rarr;M1E0S0T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+MPPT*1+MMF+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+PDN+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e5.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e596\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e46\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅱa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E0S0T0-C0\u0026rarr;M0E0S0T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+PDN+MPPT*1+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e4.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e21\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅡa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E0S0T0-C0\u0026rarr;M0E1S0TO-C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003ePDN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+PDN+MPPT*2+MMF+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e10.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E0S0T0-C2\u0026rarr;M1E0S0T0-C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+MPPT*3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+PDN+MMF+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e14.9\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e22\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅡa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM1E0S0T0-C0\u0026rarr;M0E0S1T0-C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+SGLT2i+PDN+MMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e17.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e79\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM1E0S1T0-C0\u0026rarr;M1E0S1T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+TwHF+LEF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+SGLT2i+LEF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e9.1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e51\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E0S0T0-C1\u0026rarr;M0E0S0T0-C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003ePDN+MPPT*2+CTX*3+MMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003ePDN+MPPT*1+MMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e14.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅡa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E0S0T0-C0\u0026rarr;M0E0S1T0-C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003ePDN+MPPT*1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003ePDN+MPPT*1+MMF+TAC+MZR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e9.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e40\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅡa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E0S0T0-C0\u0026rarr;M1E0S1T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+SGLT2i+PDN+MMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e15.6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e18\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E0S1TO-C1\u0026rarr;M0E0S0T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+LEF+MZR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+PDN+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e9.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e51\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E1S0T0-C1\u0026rarr;M0E1S1T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+MPPT*3+MMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+SGLT2i+MPPT*1+MMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e13.9\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅡb\u0026rarr;Ⅲb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM1E0S0T0-C0\u0026rarr;M1E1S1T0-C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+MZR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+PDN+MPPT*1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e13.1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e378\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e38\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E0S0T0-C1\u0026rarr;M0E1S1T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003ePDN+MMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+PDN+SGLT2i+MPPT*1+MMF+TAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e11.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e21\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅱa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E0S0T0-C1\u0026rarr;M0E0S0T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+LEF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+MZR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e9.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e102\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅡa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E0S0T0-C0\u0026rarr;M1E0S1T0-C0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003ePDN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+SGLT2i\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e7.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e414\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eⅢa\u0026rarr;Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eM0E1S1T0-C1\u0026rarr;M0E0S1T0-C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eRASi+PDN+MPPT*1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eRASi+SGLT2i+MPPT*2+MMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003eM\u003c/em\u003e male\u003cem\u003e;F\u0026nbsp;\u003c/em\u003efemale;\u003cem\u003eRASi\u003c/em\u003e renin angiotensin system inhibitor, \u003cem\u003ePDN\u003c/em\u003e Prednisone. \u003cem\u003eTwHF\u003c/em\u003e Tripterygium glycosides,\u003cem\u003eMPPT\u003c/em\u003e Methylprednisolone PulseTherapy,\u003cem\u003eTAC\u003c/em\u003e Tacrolimus,\u003cem\u003eMMF\u003c/em\u003e Mycophenolate Mofetil,\u003cem\u003eSGLT2i\u0026nbsp;\u003c/em\u003eSodium-Glucose Cotransporter-2 Inhibitor\u003cem\u003e, LEF\u0026nbsp;\u003c/em\u003eLeflunomide, \u003cem\u003eCTX\u003c/em\u003e Cyclophosphamide,\u003cem\u003eMZR\u003c/em\u003e Mizoribine\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eClinical and Pathological Features by outcomes\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"564\" class=\"fr-table-selection-hover\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A+B\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en=10\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup C+D\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en=9\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eAge（years）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e9.8\u0026plusmn;3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e11.5\u0026plusmn;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.318\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003eF（50%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003eF（22.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.350\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eMAP（mmHg）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e86.7（83.3,89.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e82.3（80.0,86.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.084\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eTime to first biopsy (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e19.2\u0026plusmn;4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e84.9\u0026plusmn;13.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eInter-biopsy interval (mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e86.7（83.3,89.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e82.3（80.0,86.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.540\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eHematuria(/\u0026mu;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e127.75（66.9,490.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e232.0（192.6,726.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.447\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003e24hUP (g/24 h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e0.5（0.2,1.1）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e1.3（1.1,2.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.307\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eHb（g/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e139.5\u0026plusmn;15.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e139.7\u0026plusmn;7.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.976\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eALB(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e40.2\u0026plusmn;4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e39.3\u0026plusmn;5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.706\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eScr(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e42.2\u0026plusmn;11.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e49.6\u0026plusmn;11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.179\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eUA(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e307.4\u0026plusmn;65.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e364.4\u0026plusmn;91.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.142\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eTotal cholesterol (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e4.5\u0026plusmn;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e5.2\u0026plusmn;1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.226\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eTriglyceride (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e1.6\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e1.7\u0026plusmn;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.780\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eIgG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e7.9（6.9,10.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e8.2（6.6,10.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.720\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eIgA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e2.2\u0026plusmn;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e2.5\u0026plusmn;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.325\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eIgE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e77.4（50.5,141.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e85.6（42.8,197.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.842\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eC3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e1.1\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e1.2\u0026plusmn;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.333\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eC4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e0.2\u0026plusmn;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.3\u0026plusmn;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.241\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eeGFR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e174.6\u0026plusmn;33.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e169.3\u0026plusmn;50.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.795\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026Delta;MEST-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e190.5（86.8,379.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e50（23.0,51.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.244\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026Delta;SQC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e29.5（18.8,45.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e39.0（22.0,51.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.400\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026Delta;24hUP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e0.0\u0026plusmn;2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e1.2\u0026plusmn;3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.604\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003eeGRF Slope\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e4.1\u0026plusmn;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e5.2\u0026plusmn;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0.720\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\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 vasculitis nephritis, Repeat kidney biopsy, Children, Pathological activity, Outcome","lastPublishedDoi":"10.21203/rs.3.rs-7899626/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7899626/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eImmunoglobulin A vasculitis nephritis (IgAVN) is a common childhood vasculitis with heterogeneous clinical and pathological manifestations. Repeat kidney biopsy may help assess pathological evolution and guide treatment, but its role in pediatric IgAVN remains underexplored. This study aimed to evaluate the clinicopathological changes between initial and repeat biopsies and their association with treatment response and outcomes in children with IgAVN.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis single-center retrospective analysis included 19 pediatric IgAVN patients who underwent two kidney biopsies. Clinical, laboratory, and pathological data were compared between biopsies. Pathological evaluation used ISKDC, semiquantitative classification (SQC), and Oxford Classification (MEST-C) systems. Correlations between changes in proteinuria (Δ24hUP), eGFR slope, and pathological scores (ΔSQC, ΔActivity Index, ΔChronicity Index) were analyzed. Outcomes were classified as good (A/B) or poor (C/D) based on modified Counahan criteria.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 19 pediatric patients with IgAVN were included in this study. The cohort consisted of 12 males (63.2%) and 7 females (36.8%), with a mean age at disease onset of 10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6 years. The median time from symptom onset to initial kidney biopsy was 155 days (IQR: 36, 364). A repeat kidney biopsy was performed at a median interval of 38 months (IQR: 18, 51) after the first biopsy, with the primary indications being disease recurrence (52.6%) and suboptimal treatment response (47.4%). Recurrent palpable purpura was observed in 31.6% of the patients at the time of repeat biopsy. Prior to the initial biopsy, 47.4% of the patients had received glucocorticoid therapy. The median follow-up duration for the entire cohort was 57 months (IQR: 38, 81). Microscopic hematuria improved significantly at the second biopsy (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012), while 24-hour proteinuria did not change significantly. Pathological scores (SQC, MEST-C) also showed no significant change. A strong positive correlation was found between Δ24hUP and ΔActivity Index (r\u0026thinsp;=\u0026thinsp;0.718, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). 10 patients had good outcomes and 9 had poor outcomes, but no baseline or evolution parameters significantly predicted outcome. Treatment intensity increased after repeat biopsy, with more patients receiving pulse steroids and immunosuppressants.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eRepeat kidney biopsy in pediatric IgAVN reveals discordance between clinical and pathological changes and supports its utility in guiding therapy adjustments. Proteinuria change strongly correlates with active pathological lesions, reinforcing its role in monitoring disease activity.\u003c/p\u003e","manuscriptTitle":"Repeat kidney Biopsy in 19 Children with IgA Vasculitis Nephritis: A Clinicopathological Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-18 12:14:48","doi":"10.21203/rs.3.rs-7899626/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":"7d112b71-a606-42e7-adbf-1c4da7bb83c9","owner":[],"postedDate":"November 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T10:19:11+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-18 12:14:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7899626","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7899626","identity":"rs-7899626","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}