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Abstract Background The prevalence of chronic kidney disease (CKD) is on the rise, posing a significant public health challenge. Although gut microbiome dysbiosis has been implicated in the impairment of kidney functions, the existence of pathological subtypes-linked differences remains largely unknown. We aimed to characterize the intestinal microbiota in patients with membranous nephropathy (MN), IgA nephropathy (IgAN), minimal change disease (MCD), and ischemic renal injury (IRI) in order to investigate the intricate relationship between intestinal microbiota and CKD across different subtypes. Methods We conducted a cross-sectional study involving 94 patients with various pathological patterns of CKD and 54 healthy controls (HCs). The clinical parameters were collected, and stool samples were obtained from each participant. Gut microbial features were analyzed using 16S rRNA sequencing and taxon annotation to compare the HC, CKD, MN, IgAN, MCD, and IRI groups. Results The CKD subjects exhibited significantly reduced alpha diversity, modified community structures, and disrupted microbial composition and potential functions compared to the control group. The opportunistic pathogen Klebsiella exhibited a significant enrichment in patients with CKD, whereas Akkermansia showed higher abundance in HCs. The study further revealed the presence of heterogeneity in intestinal microbial signatures across diverse CKD pathological types, including MN, IgAN, MCD, and IRI. The depression of the family Lachnospiraceae and the genus Bilophila was prominently observed exclusively in patients with MN, while suppressed Streptococcus was detected only in individuals with MCD, and a remarkable expansion of the genus Escherichia was uniquely found in cases of IRI. The study also encompassed the development of classifiers employing gut microbial diagnostic markers to accurately discriminate between distinct subtypes of CKD. Conclusions The dysregulation of gut microbiome was strongly correlated with CKD, exhibiting further specificity towards distinct pathological patterns. Our study emphasizes the significance of considering disease subtypes when assessing the impact of intestinal microbiota on the development, diagnosis, and treatment of CKD.

Abstract Renal biopsy remains the gold standard for diagnosing membranous nephropathy (MN). Recent studies have suggested that renal biopsy can be replaced with the serum phospholipase A2 receptor (PLA2R) antibody test for MN diagnosis in patients with nephrotic syndrome. However, this test has not been validated in the Chinese population. In this study, we investigated whether renal biopsy provides additional diagnostic information on patients with proteinuria who are seropositive for PLA2R antibodies (SAb +). We retrospectively reviewed the clinicopathological characteristics of SAb + adult patients (aged ≥ 18 years) with proteinuria (≥ 0.5 g/24 h) assessed at the Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, from June 2021 to March 2022. Among a total of 801 SAb + patients who received renal biopsy, those with incomplete pathological data, diabetes or any potential cause of secondary MN were excluded. Among the 491 remaining patients, 474 had primary MN (PMN), 16 had atypical MN (AMN, 9 patients with “full house” and 2 patients with HBsAg + /HBcAg + immunofluorescence results), and 1 had focal segmental glomerulosclerosis. In patients with an eGFR of ≥ 60 mL/min/1.73 m2 (n = 451), 436 had PMN, and 71 (16.3%) exhibited additional biopsy findings, with obesity-related glomerulopathy being the most common. In patients with an impaired eGFR (n = 40), 38 had PMN, and 31 (81.6%) showed additional findings, with acute tubular injury being the most common. In conclusion, anti-PLA2R antibody positivity is highly predictive of PMN in Chinese adults but often coexists with other pathological diagnoses. The advantages of renal biopsy for detecting other pathologies should be weighed against the potential risks of the biopsy procedure.

Abstract Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one‐third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end‐stage renal disease within 10 years. The identification of phospholipase A2 receptor as the primary target antigen in MN has brought about a significant shift in disease management and monitoring. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression. By synthesizing the latest research findings and clinical insights, this review seeks to contribute to the ongoing efforts to enhance our understanding and management of this challenging autoimmune disorder.

Background: Chylothorax can be classified into traumatic and nontraumatic based on the etiology. Nephrotic syndrome is a very rare cause of nontraumatic chylothorax in adults. Case presentation: A 66-year-old woman with membranous nephropathy who was non-compliant with her management, presented with dyspnea, and was found to have a large right sided chylothorax. Her chylothorax was secondary to membranous nephropathy after excluding other causes, which has been rarely reported in literature. Conclusion: This case highlights the possibility of nephrotic syndrome causing chylothorax, especially in patients with undiagnosed nephrotic syndrome or patients non-compliant with their management. When evaluating a patient with chylothorax, providers should consider nephrotic syndrome in the differential diagnosis.

Abstract Background Membranous nephropathy (MN) is a chronic glomerular disease that leads to nephrotic syndrome in adults. The aim of this study was to identify novel biomarkers and immune-related mechanisms in the progression of MN through an integrated bioinformatics approach. Methods The microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between MN and normal samples were identified and analyzed by the Gene Ontology analysis, the Kyoto Encyclopedia of Genes and Genomes analysis and the Gene Set Enrichment Analysis (GSEA) enrichment. Hub The hub genes were screened and identified by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithm. The receiver operating characteristic (ROC) curves evaluated the diagnostic value of hub genes. The single-sample GSEA analyzed the infiltration degree of several immune cells and their correlation with the hub genes. Results We identified a total of 574 DEGs. The enrichment analysis showed that metabolic and immune-related functions and pathways were significantly enriched. Four co-expression modules were obtained using WGCNA. The candidate signature genes were intersected with DEGs and then subjected to the LASSO analysis, obtaining a total of 6 hub genes. The ROC curves indicated that the hub genes were associated with a high diagnostic value. The CD4+ T cells, CD8+ T cells and B cells significantly infiltrated in MN samples and correlated with the hub genes. Conclusions We identified six hub genes (ZYX, CD151, N4BP2L2-IT2, TAPBP, FRAS1 and SCARNA9) as novel biomarkers for MN, providing potential targets for the diagnosis and treatment.

Background. Membranous nephropathy (MN) is an immunocomplex glomerular disease, which is the most common cause of nephrotic syndrome in adults. Numerous studies have established that autoantibodies against the target podocyte autoantigens, including the thrombospondin type 1 domain containing 7A (THSD7A), play a leading role in the development of idiopathic MN. Aim. To evaluate the prevalence of anti-THSD7A autoantibodies (anti-THSD7A AB) in a group of Russian patients with MN. Materials and methods. Serum titers of anti-THSD7A AB were tested in 61 patients with biopsy-proven MN and 12 healthy controls. Results. The prevalence of anti-THSD7A AB was not differing significantly in patients with MN and in the control group (110.9 [71.63; 210.62] and 159.25 [125.64; 231.97] pg/ml, respectively; p=0.111). When comparing subgroups of anti-PLA2R-negative patients and patients who did not receive immunosuppressive therapy with the control group, there were also no statistically significant differences in the Anti-THSD7A AB levels (p0.05). In the MN group, 1 (1.6%) patient was anti-THSD7A-positive: a 60-year-old man with anti-PLA2R-negative MN and the presence of hormonally inactive adenomas of both adrenal glands and colon polyps (villous adenoma with focal moderate dysplasia, tubulo-villous and tubular adenoma with focal moderate severe dysplasia). Conclusion. THSD7-associated MN is a rare variant of MN and is usually detected in PLA2R-negative patients. Screening for malignancies in THSD7A-positive MN patients is proposed.

Objective To explore the clinical significance of serum C-type lectin domain 1（CTLD1） for prognosis of patients with idiopathic membranous nephropathy（IMN）. Methods A total of 116 patients with IMN diagnosed in Shengjing Hospital from September 2016 to December 2019 were selected as the case group, and healthy volunteers with age and gender matching in the physical examination center during the same period were selected as the health control group. Clinical data of patients in case group were collected and followed up for ≥ 2 years to record treatment and outcome. The expression level of PLAZR antigen and CTLD1 antigen epitope were detected by ELISA. The differences of clinical indexes between CTLD1 positive group and negative group were compared, and the prognostic influencing factors of IMN patients were analyzed. b>Results There was a statistical difference in CTLD1 expression level between health control group and case group（P

Membranous nephropathy (MN) occurs predominantly in middle-aged and elderly individuals and ranks among the most prevalent etiologies of elderly nephrotic syndrome. As an autoimmune glomerular disorder characterized by glomerular basement membrane thickening and immune complex deposition, conventional MN animal models, including the Heymann nephritis rat model and the c-BSA mouse model, have laid a foundation for MN pathogenesis research. However, differences in target antigens between rodents and humans have impeded this work. In recent years, researchers have created antigen-specific MN animal models, primarily centered on PLA2R1 and THSD7A, employing diverse techniques that provide innovative in vivo research platforms for MN. Furthermore, significant advancements have been made in the development of in vitro podocyte models relevant to MN. This review compiles recent antigen-specific MN animal models and podocyte models, elucidates their immune responses and pathological characteristics, and offers insights into the future of MN experimental model development. Our aim is to provide a comprehensive resource for research into the pathogenesis of MN and the development of targeted therapies for older patients with MN to prolong lifespan and improve quality of life.

Abstract Background Most primary membranous nephropathy (MN) is mediated by anti-phospholipase A2 receptor (PLA2R) antibodies. Recently, these antibodies have been revealed months to years before the disease's onset. Their production and pathogenicity need further investigation. Methods Anti-PLA2R antibodies were purified from plasma of eight healthy individuals, 12 patients with PLA2R-related MN and negative circulating antibody (Ab-), and 18 patients with positive anti-PLA2R antibodies (Ab +), using affinity column coupled with recombinant human PLA2R. The antigen specificity, antibody amount, titer, IgG subclass, and affinity were assessed by Western blot, immunofluorescence, ELISA, and surface plasmon resonance. Results The natural anti-PLA2R antibodies recognized the conformational structure of PLA2R which locates on the cell membrane of podocytes. The amount of natural IgG was 0.12 ± 0.04 g/L, which accounted for 0.80% of total IgG and was lower than that of patients (2.36%, P

Background and Aim: Membranous nephropathy (MN) is a podocytopathy characterized histologically by uniform thickening of the glomerular basement membrane due to the presence of subepithelial immune deposits. This disease can occur in a transplanted kidney as a recurrence of primary (Recurrent Membranous Nephropathy, RMN) or de novo disease. Case report: A 40-year-old non-smoker man with a history of membranous nephropathy and resultant kidney failure, underwent a kidney biopsy 9 months after transplantation because of proteinuria of 4000 mg/day. Diagnosis of recurrence of membranous nephropathy in the transplanted kidney was made. The patient was given two doses of rituximab 1000 mg at a 15 day interval. Gradually, the amount of proteinuria decreased to 188 mg/day after 4 months, and his kidney function remained stable (creatinine 0.8 mg/dl) during the treatment. Conclusion: Membranous nephropathy can recur after kidney transplantation, and in cases of proteinuria more than one gram per day, we can use rituximab.

Membranous nephropathy (MN), an immune-mediated glomerular disease, is the most common cause of adult nephrotic syndrome. In MN, proteinuria is developed by podocyte damage due to the complement system activation in response to the subepithelial deposition of immune complexes containing various auto- and exogenous antigens. Membrane-attacking complex (MAC) is the terminal product of any complement pathways activation (classical, lectin or alternative) and plays the leading role in the complement-mediated podocytic damage. Thus far, the main pathway of complement activation leading to the formation of MAC in MN has not been established. The review highlights current evidence of various complement pathways activation in the development of MN, as well as recently established new molecular mechanisms of complement-mediated podocyte damage.

IgG4-related kidney disease （IgG4-RKD） is a newly recognized immune-related disease, which is involved with renal tubules and glomerulus. IgG4-RKD is sensitive to glucocorticoid （hormone） therapy. The exact pathogenesis of IgG4-RKD is still unclear. This article reported a middle-aged female patient who presented with skin pruritus and exophthalmos for over nine years and foamy urine for three months as chief complaints. This patient was diagnosed with thyroid nodules. The serum level of IgG4 was elevated up to 19 700 mg/L. Renal biopsy revealed typical pathological features （immunohistochemical staining detected dense plasmacytic infiltration in the renal stroma with infiltrating IgG4+ plasma cells > 10/high-power field）. The diagnosis of IgG4-RKD （mainly the membranous nephropathy） was considered. After hormone treatment, clinical symptoms were significantly relieved. This case suggests that during clinical diagnosis and treatment, the possibility of IgG4-RKD should be excluded for patients presenting with repeated allergy, abnormal renal function and fibrosis of related organs. Extensive attention should be paid to differential diagnosis. It is necessary to deliver routine screening of allergens for patients with allergy. Detection of IgE, IgG4, imaging and histopathological examination should be comprehensively conducted. The risk of multiple system injuries should be evaluated to deliver prompt intervention and treatment.

Stroke is one of the most severe complications of nephrotic syndrome (NS) which causes severe mortality and morbidity and patient initially presenting with stroke is rare. Here, we describe a case in which an 18-year-old female presented with ischemic stroke as an initial complication of membranous nephropathy (MN). Renal biopsy showed features of MN. This case illustrates that it is important to diagnose MN and anticoagulated this high-risk group of patients before they develop severe complications. There are only a few cases in the literature where the initial presentation of MN is ischemic stroke and it occurs in a young female patient with no risk factors apart from NS.

Hypercoagulability is a well-recognised feature of Nephrotic Syndrome (NS) and may manifest clinically in the form of Renal Vein Thrombosis (RVT), Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE); these may uncommonly be among the presenting features of the syndrome. Prompt recognition and management requires that patients with NS should be followed with a high index of suspicion for thromboembolism. Here, the authors report a case of 35-year-old male patient who, while under evaluation for proteinuria, presented with massive PE. He was eventually diagnosed with primary Membranous Nephropathy (MN); a cause of NS with the highest associated risk of thromboembolism. The patient was managed with mechanical ventilation, anticoagulation and supportive care. He also received Rituximab during hospital stay. He was discharged in stable condition on apixaban and advised close follow-up.

Objective Our objective was to explore the action mechanism of the Jinyingzi (Rosae Laevigatae Fructus)–Qianshi (Euryales Semen) couplet herbs in the treatment of membranous nephropathy (MN) based on network pharmacology.

Abstract Background Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults worldwide. A growing body of evidence indicates a pathogenic and autoimmune correlation between Helicobacter pylori infection, MN, and autoimmune liver disease. Case presentation A 47-year-old African American woman presented to our institution with epigastric pain and vomiting. In-patient hospital workup included a thorough abdominal evaluation including esophagogastroduodenoscopy and liver biopsy, which revealed active H. pylori infection and autoimmune hepatitis. The patient was incidentally also found to have nephrotic-range proteinuria. Renal workup including kidney biopsy established the diagnosis of MN. Proteinuria improved after initiation of triple therapy for H. pylori infection. Conclusion This case adds to the growing evidence of a correlation between H. pylori infection, MN, and autoimmune liver disease. This report demonstrates a unique case of a patient with MN, autoimmune hepatitis (AIH)/primary biliary cholangitis (PBC), and HP who underwent triple-eradication antibiotic treatment that resulted in an ultimate resolution of all these conditions.

Cryptococcosis is frequently found in immunosuppressed patients. It is also a significant opportunistic infection in non-immunocompromised individuals. In this study, we present a rare case of membranous nephropathy (MN) with pulmonary cryptococcosis. A 33-year-old man with MN was referred to our hospital because of dyspnea and weakness for 1 week. Before the above symptoms occurred, the dose of Cyclosporin A was increased again for relapse of MN. Multiple massive or patchy high-density shadows were present on computed tomography of the lung. Initially the patient underwent empirical anti-bacterial therapy, which turned out to be ineffective. As the results of serum cryptococcal latex agglutination tests were positive, the administration of anti-fungal drugs was prescribed. The results of fungal culture and pathologic examination of the lung tissue revealed the findings consistent with Cryptococcus neoformans. The patient was successfully treated with voriconazole followed by fluconazole with satisfactory result. Therefore, in patients with chronic kidney disease, lung lesions with poor bactericidal effects of cephalosporins need further examination to make sure whether there is pulmonary cryptococcosis. Early diagnosis and treatment might contribute to good results. It is a problem worthy of consideration that whether immunosuppressive agents need to be discontinued or not during antifungal therapy.

Background: There is variable association of membranous nephropathy (MN) with malignancy predominantly of solid organ tumours. There is debate as to how to screen and or investigate for evidence of malignancy in this group. Methods: Retrospective analysis of kidney biopsies performed between 2006 and 2016. Patients with MN were identified and clinical course including age, degree of proteinuria, histology details, treatment and rates of remission documented. Evidence of malignancy and its temporal association with MN noted. Results: Over ten-year period 216 biopsies were performed of which 20 patients (10.8%) had MN [mean age 48.5 years (range 20-82 years); there were to males]. Of these, eight patients (40%) had evidence of malignancy. Four patients were diagnosed with malignancy prior to the biopsy (mean duration 39.7 months) whereas, 4 patients were diagnosed after the biopsy (mean duration 6.7 months). Patients with MN and malignancy were older compared to those without malignancy (63.0 Vs 38.2 years) (P = 0.0054). There was no statistical difference in degree of proteinuria, focal segmental glomerulosclerosis lesions, and number of inflammatory cells in the study population. Conclusions: Higher prevalence (40%) of malignancy was associated with biopsy proven MN from Darling Downs which was statistically significant. Although age appropriate investigations are indicated in these patients, it may be prudent to actively look for evidence of underlying malignancy especially in elderly population given the concerns associated with immunosuppressive therapies.

Introduction: primary membranous nephropathy (pMN) is glomerulopathy caused in the majority of cases by autoantibodies to Phospholipase-A2 receptors (PLA2R-AB). This study aimed to evaluate the clinical course and outcomes of the patients with pMN regarding PLA2R-AB status. Patients and methods: 32 patients (21 males, 11 females) with renal biopsy-proven pMN were included in the study. PLA2R-AB (ELI SA method) and outcomes (defined according to KDIGO) were evaluated after 21 and 64 months of follow-up in 28 patients. Results: 19 patients had positive PLA2R-AB (>20 RU /ml) (59.3%), with median titer of 97 (21-1418 RU /ml). The rate of remission in low PLA2R-AB titer group (< 200 RU /ml) after 21 months was significantly higher than in high PLA2R-AB group (> 200 RU /ml) (90% vs. 50%, p=0.045), and after 64 months the difference was not significant (80% vs. 50%, p=0.210). The relapse rate after 64 months was higher in the high PLA2R-AB group (87% vs. 63%). Multivariant linear regression found serum creatinine (ß=0.682, p

Introduction Membranous nephropathy (MN) is an organ-specific autoimmune disease, and its prevalence is increasing. B lymphocytes activated by T cells produce antibodies. CD19+/CD20+ plasma cells may contribute to autoantibody and alloantibody production. Rituximab has been effective in treating MN in many clinical trials. Thus, we conducted a meta-analysis to explore the clinical efficacy and safety of rituximab with MN. Material and methods We searched Embase, PubMed, Cochrane Library and ClinicalTrials.gov without language or publication date limitations. Studies were classified in high-risk, medium-risk and low-risk groups based on baseline proteinuria. Follow-up periods and different administrations of rituximab were also compared. Complete remission (CR) and partial remission (PR) were assessed to measure the efficacy of rituximab, and adverse effects were also extracted. Dichotomous data were expressed by the odds ratio (OR), and the 95% confidence intervals (95% CI) were used for the recruited studies. Results Fourteen articles, including 17 studies, were included in this meta- analysis. The pooled OR of overall PR and CR remission rate was 0.58 (95% CI: 0.53–0.63; p = 0.003). No studies belonged to the low-risk group. The overall PR and CR remission rate in the medium-risk group was 0.56 (95% CI:0.36–0.73; p = 0.57). The pooled OR of overall PR and CR remission rate in the high-risk group was 0.59 (95% CI: 0.53–0.65; p = 0.03). At the 12-month follow-up, the pooled OR of overall PR and CR remission rate was 0.51 (95% CI:0.43–0.59; p = 0.72). At the 24-month follow-up, the pooled OR of overall PR and CR remission rate was 0.71 (95% CI: 0.48–0.86; p = 0.07). The pooled OR of efficacy of rituximab at 375 mg/m2 × 4 was 0.63 (95% CI: 0.55–0.70; p = 0.001). Rituximab was tolerated in MN, and most adverse effects were mild. The pooled OR of infusion reaction rate of rituximab was 0.25 (95% CI: 0.13–0.44; p = 0.01) in MN. The pooled OR of cardiovascular-related event rate of rituximab in MN was 0.04 (95% CI: 0.02–0.11). The pooled OR of infection rate of rituximab in MN was 0.06 (95% CI: 0.03–0.12; p < 0.00001). Conclusions Rituximab is safe and effective in MN and a promising alternative treatment. More randomized control trials and studies on the role of MN are expected.

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Since the moment of animal model creation and the recognition of podocytes damage as a key mechanism of MN development, the identification of antigens, first of all the phospholipase A2 receptor (PLA2R), and the development of methods of PLA2R autoantibodies detection and its monitoring opened a new era in the idiopathic MN (iMN) diagnosis, treatment and prognosis evaluation. MN continues to be actively studied in the new millennium, since a number of aspects of its pathogenesis still need to be clarified, and there is still no clear opinion on the iMN treatment optimal approach. Comprehensive clinical and serological assessment of patients with iMN can be the key to individual choice of treatment protocols. In patients with aPLA2R-positive iMN, the predictor of disease remission is the aPLA2R titer decrease or aPLA2R disappearance in the blood serum, and disease relapse is associated with the aPLA2R appearance ore increase of aPLA2R titer in the circulation. Studies which were conducted by today (GEMRITUX, MENTOR, STARMEN, NICE, etc.) confirmed the acceptable safety profile and effectiveness of iMN therapy by anti-CD20 monoclonal antibodies (rituximab): more than half of of iMN patients had remission of nephrotic syndrome or proteinuria decrease, remissions in anti-CD20 monoclonal antibodies treated patients were longer compared to traditional therapy. The obtained data allows us to consider rituximab and anti-CD20 antibody therapy of a new generation not only as an alternative to the more toxic treatment with cyclophosphane and calcineurin inhibitors, but as an independent promising direction of therapy for patients with IMN, which completely changes the paradigm of treatment of this glomerulopathy.

Vaccination against the SARS-CoV-2 virus (COVID-19) has proven to be the most effective measure to prevent the spread and reduce infection severity. A case report of de novo membranous nephropathy (MN) following immunization with inactivated virus vaccine (CoronaVac®, Sinovac Biotech) is presented here. A 53-year-old man presented with a sudden onset of leg edema a week after receiving an inactivated virus vaccine and a relapse of nephrotic syndrome (NS) with acute kidney injury (AKI) after a booster dose. Screening for serum anti-phospholipase A2 receptor antibody and secondary causes of MN were negative. Kidney biopsy revealed an early MN pattern with focal spike formation, whilst numerous subepithelial electron-dense deposits and a few small deposits in the mesangial area were observed through electron microscopy. A short course of steroids and oral cyclophosphamide was prescribed, resulting in the complete remission of NS and AKI. MN following SARS-CoV-2 vaccination should call for medical importance. Awareness of the association between vaccination and MN should be kept in mind to avoid unnecessary treatment with long-term immunosuppressive agents.

Key Clinical Message Membranous nephropathy associated with malignant neoplasm may remit completely with treatment of the underlying disease. In such cases, recurrence is very rare. However, after a recurrence, attention should be paid to the possible recurrence of the underlying disease.

Abstract Background Patients with Idiopathic membranous nephropathy (IMN) have various outcomes. The aim of this study is to construct a tool for clinicians to precisely predict outcome of IMN. Methods IMN patients diagnosed by renal biopsy from Shanghai Ruijin Hospital from 2009.01 to 2013.12 were enrolled in this study. Primary outcome was defined as a combination of renal function progression [defined as a reduction of estimated glomerular filtration rate (eGFR) equal to or over 30% comparing to baseline], ESRD or death. Risk models were established by Cox proportional hazard regression analysis and validated by bootstrap resampling analysis. ROC curve was applied to test the performance of risk score. Results Totally 439 patients were recruited in this study. The median follow-up time was 38.73 ± 19.35 months. The enrolled patients were 56 (15–83) years old with a male predominance (sex ratio: male vs female, 1:0.91). The median baseline serum albumin, eGFR-EPI and proteinuria were 23(8–43) g/l, 100.31(12.81–155.98) ml/min/1.73 m2 and 3.98(1.50–22.98) g/24 h, respectively. In total, there were 36 primary outcomes occurred. By Cox regression analysis, the best risk model included age [HR: 1.04(1.003–1.08), 95% CI from bootstrapping: 1.01–1.08), eGFR [HR: 0.97 (0.96–0.99), 95% CI from bootstrapping: 0.96–0.99) and proteinuria [HR: 1.09 (1.01–1.18), 95% CI from bootstrapping: 1.02–1.16). One unit increasing of the risk score based on the best model was associated with 2.57 (1.97–3.36) fold increased risk of combined outcome. The discrimination of this risk score was excellent in predicting combined outcome [C statistics: 0.83, 95% CI 0.76–0.90]. Conclusions Our study indicated that older IMN patients with lower eGFR and heavier proteinuria at the time of renal biopsy were at a higher risk for adverse outcomes. A risk score based on these three variables provides clinicians with an effective tool for risk stratification.

A 16-year-old girl with no history of renal disease had a fever of 38 °C after her second HPV vaccination and was identified as positive for proteinuria. As she maintained urinary protein of 3.10 g/gCr and 5–9 urinary red blood cells/HPF, a renal biopsy was performed and small spikes on PAM staining with the granular deposition of IgG1++ and IgG3+ on the glomerular capillary wall were discovered by immunofluorescence, although PLA2R immunostaining was negative. Analysis by electron microscope showed electron density deposition in the form of fine particles under the epithelium. The diagnosis was secondary membranous nephropathy stage II. Immunostaining with the anti-p16 INK4a antibody was positive for glomerular cells, and Western blot analysis of urinary protein showed a positive band for p16 INK4a. However, laser-microdissection mass spectrometry analysis of a paraffin section of glomeruli failed to detect HPV proteins. It is possible that the patient was already infected with HPV and administration of the HPV vaccine may have caused secondary membranous nephropathy.

Introduction. Pregnancies in women with membranous nephropathy (MN) are usually complicated by increased proteinuria and superimposed preeclampsia, and this frequently results in poor pregnancy outcomes. The aim of this paper is to present case series of pregnant women with MN and different fetal and maternal outcomes. Outline of cases. Case 1 presents a 25-year-old woman with MN, who had relapsed nephrotic syndrome in early pregnancy with proteinuria of 4.14 g/day and serum albumin of 30 g/L accompanied by hypertension. Due to a missed abortion, the pregnancy was terminated. Three months later her proteinuria was still increased, measuring 3 g/day. Case 2 presents a 29-year-old woman with a history of diffuse proliferative glomerulonephritis, who conceived with proteinuria below 0.5 g/day. The proteinuria ranged between 1 and 2 g/day from the 32nd until the 38th gestational week, when she delivered a healthy neonate. After delivery, the woman underwent a kidney biopsy, which revealed MN. Case 3 presents a 25-year-old woman with MN, whose proteinuria was 1 g/day at the time of conception, but in the 35th gestational week proteinuria of 4.2 g/day was noticed. In the 36th gestational week, increased proteinuria was detected, and a cesarean section was performed with favorable neonatal outcome. After two weeks her proteinuria dropped to 0.6 g/day. Conclusion. Pregnancies in women with MN associated with low-grade proteinuria at the time of conception may have a favorable perinatal outcome. Such pregnancies require multidisciplinary management by both obstetricians and nephrologists, and team decision regarding the best timing of delivery.

Membranous nephropathy (MN) is a chronic form of glomerulonephritis, associated with the presence of immune complexes beneath the podocytes on the subepithelial region of glomerular capillaries. MN is not a disease entity but one of relatively common patterns of glomerular injury that may be a manifestation of primary renal autoimmunological reaction or may evolve as a phenomenon secondary to wide spectrum of systemic processes.

Objective: Systematic review of the clinical efficacy of medicinal nephropathy in the treatment of membranous nephropathy with the addition of traditional Chinese herbal compound on the basis of hormone and immunosuppressive therapy. Methods: Computer search of China Knowledge Network, Wanfang Database, Weipu Database, China Biomedical Database, PubMed Database Embase Database Cochrane Database, collect clinical research on Chinese medicine compound + hormone + immunosuppressive therapy for MN, delete duplicate literature, eliminate non-conformity by reading topic, abstract and full text The literature was included in the exclusion criteria, the data was extracted from the included literature, and the meta-analysis was performed using the stata14.0 software package. Results: The top 6 Chinese medicines used were Astragalus, Poria, Atractylodes, Salvia, Angelica and Chinese Yam. The use of traditional Chinese medicine in the treatment of patients with MN on the basis of hormone and immunosuppressive therapy can improve clinical efficacy[OR=2.90,95%CIï2.27, 3.70ï,P < 0.00001]and TCM symptom efficacy [OR=3.10,95%CIï1.91, 5.05ï,P < 0.00001], improved TCM syndrome scores [SMD=-0.93,95%CIï-1.34, -0.52ï,P < 0.00001], reduced 24-hour urine protein levels[SMD=-0.90,95%CIï-1.23, -0.57ï,P < 0.00001], increased plasma albumin levels[SMD=1.22,95%CIï0.86, 1.58ï,P = 0.000], decreased blood lipid TC levels[SMD=- 0.69,95%CIï-0.98, -0.39ï,P< 0.00001], lowering blood lipid TG levels[SMD=-0.75,95%CI ï-1.09, -0.41ï,P < 0.0001], in improving renal function BUN levels[SMD=-0.56,95%CI ï-0.97, 0.14ï,P = 0.008] and Scr levels [SMD=-0.58,95%CIï-0.89, -0.27ï,P = 0.0002], reducing the incidence of adverse reactions [OR=0.25,95%CIï0.17, 0.36ï,P < 0.00001]. Egger and harbord test results suggest that some indicators have publication bias. Conclusion: The traditional Chinese medicine used is mainly jaundice, and the traditional Chinese medicine for replenishing qi and activating blood is used more frequently. In the basic application of hormone + immunosuppressive agents, Yiqihuoxue Chinese medicine has a good effect on MN, but it is limited to the quality of the included literature. The conclusion needs to be verified by more high-quality studies. [ABSTRACT FROM AUTHOR]

Introduction/Objective. An unfavorable prognosis of membranous nephropathy (MN) is determined by the presence of persistent proteinuria and extensive tubulointerstitial lesions at initial biopsy. Our study investigated the value of markers of renal cell dysfunction (glomerular filtration rate, urinary excretion of protein, ectoenzyme proximal tubular epithelial cells, and oxidative stress) in patients with MN, and points to the use of these markers in a possible therapeutic modification. Methods. The study included 28 patients with MN and 30 healthy individuals as control. In addition to the basic laboratory studies, enzyme [aminopeptidase N (APN), plasma cell glycoprotein-1 (PC-1), N-acetyl- β-D-glucosaminidase (NAGA), and dipeptidyl peptidase-4] activity was determined in serum and urine, as well as parameters of oxidative damage [thiobarbituric acid concentration of substance-responders (TBARS), malondialdehyde, and the concentration of the total sulfhydryl (SH) group]. Results. In patients with MN, serum activity of PC-1 and APN and urinary excretion of NAGA were significantly higher than in the control group. Also, significant correlation between daily proteinuria and serum PC-1 activity and urinary excretion of NAGA was found in patients with MN. Serum and urine levels of TBARS as well as total SH group levels were significantly lower in patients with MN than in healthy controls. Conclusion. Kidney damage in MN is accompanied by the release of several tubular enzymes, with potential diagnostic and prognostic significance. The study suggests a possible role of oxidative stress in pathogenesis of MN and the use of antioxidants in preventing impairment as part of future therapy. [Project of the Ministry of Science and Environmental Protection of Serbia, Grant No. 175092]

Abstract Background Nephrotic syndrome (NS) is a nonspecific kidney disorder, commonly caused by minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN). Here we analyzed urinary protein profiles, aiming to discover disease-specific biomarkers of these three common diseases in NS. Methods Sixteen urine samples were collected from patients with biopsy-proven NS and healthy controls. After removal of high-abundance proteins, the urinary protein profile was analyzed by LC–MS/MS to generate a discovery set. For validation, ELISA was used to analyze the selected proteins in 61 urine samples. Results The discovery set included 228 urine proteins, of which 22 proteins were differently expressed in MCD, MN, and FSGS. Among these, C9, CD14, and SERPINA1 were validated by ELISA. All three proteins were elevated in MCD, MN, and FSGS groups compared with in IgA nephropathy and healthy controls. When a regression model was applied, receiver operating characteristic analysis clearly discriminated MCD from the other causative diseases in NS. Conclusions We developed a disease-specific protein panel that discriminated between three main causes of NS. Through this pilot study, we suggest that urine proteomics could be a non-invasive and clinically available tool to discriminate MCD from MN and FSGS.

Background: According to the renal phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (iMN) could be categorized into PLA2R-associated and non-PLA2R-associated iMN. This study aimed to examine whether the non-PLA2R-associated iMN had any difference in clinical features compared with PLA2R-associated iMN. Methods: A total of 231 adult patients diagnosed as iMN were recruited to this retrospective study. Renal PLA2R expression was examined by immunofluorescence. Among these patients, 186 (80.5%) with complete baseline clinical data were used for further study. Urinary protein excretion, serum albumin, and creatinine were analyzed. For those patients with follow-up longer than 1 year, the relationship between PLA2R and response to immunosuppressants were analyzed. The t-test was used for parametric analysis and the Mann-Whitney U-test was used for nonparametric analysis. Categorical variables were described as frequencies or percentages, and the data were analyzed with Pearson's Chi-square test or Fisher's exact test. Results: Of the 231 iMN patients, 189 showed renal detectable PLA2R expression (81.8%). The baseline serum creatinine, serum albumin, and urine protein excretion were not significantly different between PLA2R-associated (n = 145) and non-PLA2R-associated iMN patients (n = 41). However, about 1/3 of the non-PLA2R-associated iMN had abnormal serological tests, significantly more common than PLA2R-associated iMN (31.7% vs. 8.3%, P = 0.000). The non-PLA2R-associated iMN had lower C4 levels compared with PLA2R-associated iMN (P = 0.004). The non-PLA2R-associated iMN patients also showed a better response to immunosuppressants (complete remission [CR] 42.9%; partial remission [PR] 14.3%) compared with PLA2R-associated iMN (CR 3.2%; PR 48.4%, P = 0.004) at the 3rd month. Conclusions: There were no significant differences in serum creatinine, albumin, and urine protein excretion between PLA2R-associated and non-PLA2R-associated iMN, while the non-PLA2R-associated iMN patients showed more abnormal serological tests. The non-PLA2R-associated iMN seemed to respond more quickly to the immunosuppressive therapy compared with PLA2R-associated iMN.

Introduction. Pulmonary embolism (PE) is a serious complication of deep venous thrombosis, with a significant morbidity and mortality. More often, PE complicates the course of the nephrotic syndrome (NS), in particular when the disease is active, but it may occur as the first sign of illness when the diagnosis of the NS is being delayed as a result. Membranous nephropathy is, generally speaking, the most commonly reported glomerulonephritis associated with the increased risk of thrombosis. Case outline. This report summarizes our experience with three young male patients (a 26-year-old, a 22-year-old, and a 45-year-old), in which PE was the first presenting feature of the NS. All of them were admitted to the hospital experiencing chest pains, dry cough, and shortness of breath. One of them had high temperature and the other two swelling of the lower parts of legs. Computed tomography of the thorax showed pulmonary artery thrombosis in all three patients. Diagnosis of the NS was confirmed by laboratory analysis, while renal biopsy showed membranous nephropathy. The treatment was based on the pulse of methylprednisolone (1.5 g over a period of three days), with alternating therapy of oral corticosteroids and cyclophosphamide on a monthly basis during six months. After six months, two patients reached incomplete remission, while the third one still has the NS and normal renal function. Conclusion. Not so rare occurrence of thromboembolic events in the NS suggests that one should always suspect the NS in all patients with deep venous thrombosis or PE.

The review highlights the evolution of ideas on the mechanisms responsible for the development of membranous nephropathy (MN), glomerulopathy that is the most common cause of nephrotic syndrome in adults. Primary emphasis is placed on the primary form of MN. The important step to understanding the nature of this clinical and morphological form of glomerulonephritis is to create its animal model (Heymann nephritis), then to decipher the mechanisms of immune complex damage (complement activation, a role of cellular immunity), and to identify autoantigens responsible for the development of idiopathic MN in man (podocyte neutral endopeptidase, transmembrane M-type phospholipase A2 receptor, thrombospondin type-1 domain-containing 7A. The findings constituted the basis for developing current methods for the diagnosis and treatment of MN, including the pathogenetically sound inhibition of autoantibody production, as well as a molecular orientation effect on podocyte dysfunction.

Background Renal biopsies performed in diabetic patients are increasing and becoming more complex. Comprehensive data on modern spectrum of biopsy-proven renal disease in Chinese diabetic patients are lacking. Methods In a nationwide renal biopsy survey including 71,151 native biopsies from 2004 to 2014, diabetic patients were identified according to the clinical diagnosis from referral records. The clinical data were extracted from referral records and pathological reports. Results A total of 1,604 diabetic patients, including 61 patients with T1DM, were analyzed in this study. The median age is 51.39 ± 11.37 years. Male patients accounted for 58% of the population. We found that only 44.7% of diabetic patients had the isolated pathological diagnosis of diabetic nephropathy (DN), while 49.1% had non-diabetic renal disease (NDRD) alone, and 6.2% had NDRD superimposed on DN. Nephrotic syndrome (n = 824, 51.4%) was the most common clinical indication for renal biopsy. Among 887 patients with NDRD, membranous nephropathy (n = 357) was the leading diagnosis, followed by IgA nephropathy (n = 179). Hypertensive renal disease (n = 32), tubulointerstitial nephropathy (n = 27) and acute tubular necrosis (n = 16) accounted for 3.5%, 2.9%, 1.7% of the NDRD cases respectively. Nearly a half (49.2%) of patients with T1DM had NDRD. Discussion Over 55% diabetic patients with kidney disease were diagnosed as non-diabetic renal disease, among which MN and IgAN were the most common two pathological types.