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Stem and progenitor cells have been observed to contribute to regenerative processes in acute renal failure and chronic kidney disease. Recent research has delved into the intricate mechanisms by which stem and progenitor cells exert their influence on kidney diseases. Understanding how these cells integrate with the existing renal architecture and their response to injury could pave the way for innovative treatment strategies aimed at promoting kidney repair and regeneration. Overall, the role of stem and progenitor cells in kidney diseases is multifaceted, with their ability to contribute to tissue regeneration, immune modulation, and the maintenance of renal homeostasis. Here, we review the studies that we have available today about the involvement of stem and progenitor cells both in regenerative therapies and in the causes of renal diseases, as well as in natural healing mechanisms, taking into account the main kidney disorders, such as IgA nephropathy, lupus nephritis, diabetic nephropathy, C3 glomerulopathy, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and ANCA-associated crescentic glomerulonephritis. Moreover, based on the comprehensive data available in the framework of the specific kidney diseases on stem cells and renal progenitors, we hypothesize a possible role of adult renal progenitors in exacerbating or recovering the illness. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of body mass index (BMI) on the clinicopathological characteristics of patients with idiopathic membranous nephropathy (IMN). Methods A total of 261 patients with IMN were divided into the normal group (66 cases), the overweight group (105 cases) and the obese group (90 cases) according to BMI. Clinical and renal pathological data of patients were compared between the three groups. The correlation between BMI and clinicopathological indexes was analyzed by Pearson or Spearman's correlation. The influencing factors of estimated glomerular filtration rate (eGFR) were analyzed by multiple linear regression, and the influencing factors of interstitial fibrosis (IF), tubular atrophy (TA), glomerulosclerosis (GS) and mesangial cell proliferation (MCP) were analyzed by binary Logistic regression. Results Compared with the normal group, the prevalence of diabetes mellitus, triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were elevated in the overweight group. The prevalence of hypertension, hemoglobin (HGB), uric acid (UA), LDL-C, TG, 24-h urinary protein (UTP) and serum complement 3 (C3) were elevated, and high-density lipoprotein cholesterol (HDL-C) was decreased in the obese group (P＜0.05). The prevalence of hypertension, UA, TG and serum C3 were elevated in the obese group compared to the overweight group (P＜0.05). The glomerular basement membrane (GBM) thickness was higher in the obese group and the overweight group than that in the normal group, and the proportion of GS and IF was higher in the obese group than that in the normal group (P＜0.05). BMI was positively correlated with hypertension, TG, LDL-C, serum C3, UTP, GS, IF, MCP and deposition in the mesangial region of C3, and negatively correlated with HDL-C (P＜0.05). Multiple linear regression analysis showed that age, blood urea nitrogen (BUN), anti-phospholipase A2 receptor antibody (anti-PLA2R), UTP and TA were independent risk factors of eGFR. Binary Logistic regression analysis showed that elevated BMI, age, UTP and serum creatinine (Scr) were independent risk factors for IF. Age, Scr and elevated UA were independent risk factors for TA. Elevated BMI and decreased eGFR were independent risk factors for GS. Elevated BMI was an independent risk factor for MCP. There was no significant difference in the treatment protocol of IMN patients between the three groups. Conclusion Obesity can exacerbate multiple clinical and pathological outcomes in IMN patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between Pan-immune inflammation Value(PIV) and hypercoagulable state in patients with idiopathic membranous nephropathy (IMN). Methods Clinical data of 280 patients diagnosed with IMN idiopathic membranous nephropathy who underwent renal biopsy at the Department of Nephrology, Affiliated Hospital of Xuzhou Medical University from February 2020 to February 2021 were retrospectively analyzed. Patients were categorized into the hypercoagulable group (89 cases) and the control group (191 cases) based on criteria for hypercoagulability, and baseline clinical data between the two groups were compared. Results Binary logistic regression analysis revealed that PIV level (OR=1.002. 95%CI 1.000-1.004,P=0.016),total cholesterol(OR=1.398.95% CI 1.190-1.642,P<0.001),and antithrombin III activity(OR=0.903,95%CI 0.871-0.936, P<0.001) were independent risk factors for hypercoagulable state in IMN patients. Conclusion PIV is an independent risk factor for hypercoagulable state in patients with IMN. Early assessment of PIV levels in IMN patients with higher PIV levels can aid in evaluating their coagulation status and initiating preventive measures such as anticoagulation therapy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between serum aproliferation inducing ligand (APRIL), monocyte chemoattractant protein-1 (MCP-1), CD4+/CD8+ ratio and immunosuppressive therapy efficacy in patients with idiopathic membranous nephropathy (IMN). Methods: 167 IMN patients who received immunosuppressive therapy in Loudi Hospital Affiliated to South China University from January 2020 to March 2022 were selected as the research objects. The levels of serum APRIL and MCP-1 before treatment were detected by enzyme-linked immunosorbent assay (ELISA), CD4+ and CD8+ were detected by flow cytometry, and the ratio of CD4+/CD8+ was calculated. Patients were divided into effective group (n=126) and ineffective group (n=41) according to the curative effect after treatment, the serum APRIL, MCP-1 and CD4+/CD8+ ratio were compared between two groups. The influencing factors of the efficacy of immunosuppressive therapy for IMN were analyzed by Logistic regression model, the predictive value of serum APRIL, MCP-1 and CD4+/CD8+ ratio for ineffective immunosuppressive therapy was analyzed by receiver operating characteristic (ROC) curve. Results: The serum APRIL, MCP-1 and CD4+/CD8+ ratio in ineffective group were higher than those in effective group (P<0.05). Univariate analysis showed that, the efficacy of immunosuppressive therapy in IMN patients was related to pathological stage, 24 h urine protein, serum creatinine (Scr), cystatin C (CysC), and glomerular filtration rate (GFR) (P<0.05). Multivariate Logistic regression analysis showed that, elevated serum APRI, MCP-1, CD4+/CD8+ ratio and pathological stage III and IV were independent risk factors for ineffective immunosuppressive therapy for IMN (P<0.05). The area under the curve (AUC) of serum APRIL, MCP-1, CD4+/CD8+ ratio and combined detection for predicting ineffective immunosuppressive therapy in IMN patients were 0.815, 0.811, 0.749 and 0.939 respectively, the predictive value of combined detection was better than that of each index alone. Conclusion: The increase of serum APRIL, MCP-1 and CD4+/CD8+ ratio are independent risk factors for the ineffective treatment of IMN immunosuppressive agents, the combine detection of the three indicators has a high predictive value for the efficacy of IMN immunosuppressive agents. [ABSTRACT FROM AUTHOR]

Background: Because spontaneous remission is common in IMN, and there are adverse effects of immunosuppressive therapy, it is important to assess the risk of progressive loss of renal function before deciding whether and when to initiate immunosuppressive therapy. Therefore, this study aimed to establish a risk prediction model to predict patient prognosis and treatment response to help clinicians evaluate patient prognosis and decide on the best treatment regimen. Methods: From September 2019 to December 2020, a total of 232 newly diagnosed IMN patients from three hospitals in Liaoning Province were enrolled. Logistic regression analysis selected the risk factors affecting the prognosis, and a dynamic online nomogram prognostic model was constructed based on extreme gradient boost, random forest, logistic regression machine learning algorithms. Receiver operating characteristic and calibration curves and decision curve analysis were utilized to assess the performance and clinical utility of the developed model. Results: A total of 130 patients were in the training cohort and 102 patients in the validation cohort. Logistic regression analysis identified four risk factors: course ≥ 6 months, UTP, D-dimer and sPLA2R-Ab. The random forest algorithm showed the best performance with the highest AUROC (0.869). The nomogram had excellent discrimination ability, calibration ability and clinical practicability in both the training cohort and the validation cohort. Conclusions: The dynamic online nomogram model can effectively assess the prognosis and treatment response of IMN patients. This will help clinicians assess the patient's prognosis more accurately, communicate with the patient in advance, and jointly select the most appropriate treatment plan. [ABSTRACT FROM AUTHOR]

Introduction: Patients with idiopathic membranous nephropathy (IMN) are particularly susceptible to thromboembolism (TE). The phospholipase A2 receptor (PLA2R) antibody (Ab) has been indicated to work as an independent risk predictor for venous TE in IMN. This study aimed to further explore the predictive value of PLA2R Ab for both venous and arterial TE in IMN patients. Methods: A total of 91 IMN patients were retrospectively selected and divided into anti-PLA2R-positive or anti-PLA2R-negative groups according to the anti-PLA2R Ab titer (cutoff: 20 RU/mL). Serum PLA2R Abs were estimated using ELISA. Anti-PLA2R-positive IMN patients were further assigned into two groups based on the presence or absence of TE. Results: Twelve (18.18%) IMN patients with anti-PLA2R positivity had TE, including both venous and arterial TE. No TE occurred in the anti-PLA2R-negative group. IMN patients in the anti-PLA2R-positive group had significantly higher levels of total cholesterol and low-density lipoprotein than those in the anti-PLA2R-negative group. No significant difference was observed in the anti-PLA2R Ab titer between patients with and without TE. Patients with TE were significantly older than those without TE. Conclusion: This study demonstrates that the positive status of anti-PLA2R Abs contributes to thrombosis formation in IMN. [ABSTRACT FROM AUTHOR]

Background: Although, several studies have assessed the association of the phospholipase A2 receptor (PLA2R) and HLA-DQA1 SNPs with primary membranous nephropathy (PMN), results were inconsistent and between-studies heterogeneity needs to be investigated. Objectives: The aim of this review was to summarize existing data on the contribution of 10 SNPs in the PLA2R and HLA-DQA1 genes to PMN susceptibility and to investigate the between-studies heterogeneity by subgroup analyses and meta-regressions. Design: This study was performed according to the PRISMA guidelines for systematic reviews and meta-analyses. Data sources and methods: An electronic literature search for eligible studies among all papers published prior to January 10, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the 10 following SNPs: rs4664308, rs3749117, rs3749119, rs35771982, rs3828323, rs16844715, rs1511223, rs6757188, rs2715918, and rs2187668. Results: Combined analyses revealed a significant increase in PMN risk conferred by the following alleles: rs4664308*A, rs3749117*T, rs3749119*C, rs35771982*G, rs3828323*C, rs16844715*C, rs1511223*A, rs2715918*A, and rs2187668*A, all P -values <.001. Moreover, the PLA2R-rs4664308/HLA-DQA1-rs2187668 interaction was significantly associated with an increased PMN risk, P <.001. However, there was a substantial between-studies heterogeneity for some SNPs. Subgroup analyses by ethnicity for the 9 PLA2R SNPs did not show any cross-ethnic disparity. Inversely, the risk conferred by the HLA-DQA1 rs2187668*A allele was significantly higher in Caucasians (OR [95% CI] = 3.929 [3.251–4.748]) than in Asians (OR [95% CI] = 2.537 [1.94–3.318], P =.007. Besides, meta-regressions revealed for the majority of investigated SNPs significant correlations of the effect size with albumin, 24-hours proteinuria, serum creatinine, and eGFR levels. Hence, the influence on PMN risk conferred by the PLA2R and HLA-DQA1 SNPs was rather noted in patients with a severe disease. Conclusion: This meta-analysis showed that 9 out of the 10 investigated SNPs in PLA2R and HLA-DQA1 genes were associated with increased PMN risk. Heterogeneity could be due to disparate patient groups in terms of disease presentation for almost all SNPs, and ethnicity for the HLA-DQA1 rs2187668 SNP. Registration: This review has been registered on PROSPERO: CRD42024506729. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506729 Plain language summary: Genetic factors in primary membranous nephritis Why was the study done? Primary membranous nephritis (PMN) is the most common etiology of adult-onset nephrotic syndrome. Understanding risk factors, particularly genetic ones, would provide a better understanding of its pathophysiological mechanisms in order to prevent and treat patients more effectively. What did the researchers do? The research team summarized published data on genetic factors associated with PMN including phospholipase A2 receptor (PLA2R) and HLA-DQA1 genes. What did the researchers find? The total number of included studies was 27. Nine out of ten genetic factors were found to be associated with PMN risk. Moreover, we noted significant interaction between PLA2R and HLA-DQA1 in potentializing PMN risk. Nevertheless, there was a significant between-studies heterogeneity which was found to be explained in part by disease severity. What do the findings mean? This study has identified some important some genetic factors associated with PMN together with confounding factors that could influence the aforementioned association. [ABSTRACT FROM AUTHOR]

Background: Idiopathic membranous nephropathy (IMN) is a leading cause of end-stage renal disease (ESRD). The purpose of this study was to evaluate whether urinary albumin-to-creatinine ratio (UACR) diurnal variation rate calculated by spot urinary protein test predicts 1-year nephrotic outcomes as a biomarker of proteinuria severity in patients with IMN. Methods: Patients' baseline demographics, blood and urinary biomarkers, and clinical and pathological characteristics were collected retrospectively. Urine samples were collected at 7:00 (before breakfast) and 19:00 (after dinner) to calculate the UACR diurnal variation rate. A prediction model for no remission (NR) was developed statistically based on differences between prognosis groups. Receiver operating characteristic curve (ROC) analysis was performed to evaluate prediction abilities and determine optimal cut-off points of the model and UACR diurnal variation rate alone. Results: The formula for calculating the probability of NR was exp(L)/(1 + exp(L)), where the linear predictor L = – 22.038 + 0.134 × Age (years) + 0.457 × 24-h urinary protein + 0.511 × blood urea nitrogen (BUN) + 0.014 × serum uric acid (SUA) + 2.411 if glomerular sclerosis + 0.816 × fasting blood glucose (FBG)-0.039 × UACR diurnal variation rate (%). Optimal cut-off points for NR prediction by the final model and UACR diurnal variation rate alone were 0.331 and 58.5%, respectively. Sensitivity and specificity were 0.889 and 0.859 for the final model, and 0.926 and 0.676 for UACR diurnal variation rate alone. Conclusion: UACR diurnal variation using spot urinary protein is a simpler way to predict nephrotic outcomes and is a highly sensitive screening tool for identifying patients who should undergo further comprehensive risk assessment. [ABSTRACT FROM AUTHOR]

Objective: This study aims to elucidate the role of T follicular helper (Tfh) cells and their subsets in idiopathic membranous nephropathy (IMN). Methods: The frequencies of Tfh cell subsets and B cell subsets in peripheral blood (PB) were detected in both IMN patients and healthy controls (HCs). The involvement of Tfh cells in the disease pathogenesis was examined by coculturing human Tfh cells with B cells. The dynamic changes of Tfh cells in PB or spleen were monitored in passive Heymann nephritis (PHN) rats. Results: The frequencies of circulating Tfh (cTfh) cells, cTfh2 cells, and plasmablasts were enriched in the PB of patients with IMN. cTfh cells expressed higher ICOS, and lower BTLA than healthy counterparts. The frequency of ICOS + cTfh2 was associated with the severity of IMN, including 24h urine protein, IgG4 concentration and the IgG4: IgG ratio. Positive correlations were also observed between the frequency of cTfh2 cells with plasmablasts, serum IL-21 and IL-4 levels. Importantly, cTfh cells isolated from IMN patients were able to induce the differentiation of B cells to memory B cells (MBC) and plasmablasts, this process could be substantially attenuated by blocking the IL-21. Similar increases of ICOS + cTfh cells were also detected in spleen of PHN rats, concomitant with elevated urine protein levels. Conclusions: Collectively, our results demonstrate that the imbalance of cTfh cell subsets play a crucial pathogenic role in IMN by inducing the differentiation of B cells through IL-21, and cTfh2 cells might serve as useful markers to evaluate the progression of IMN. [ABSTRACT FROM AUTHOR]

Membranous nephropathy constitutes approximately 20% of adult nephrotic syndrome cases. In approximately 80% of cases, membranous nephropathy is primary, mediated by IgG autoantibodies primarily targeting podocyte antigens (PLA2R, THSD7A, etc.). The treatment involves a combination of corticosteroids and cyclophosphamide or anti-CD20-based therapies, e.g., rituximab. In the event of significant proteinuria and in order to avoid the urinary elimination of rituximab, therapeutic apheresis, in particular semi-specific immunoadsorption, may be an option allowing for a reduction in proteinuria and autoantibodies before initiating treatment with rituximab. We present the preliminary experience of three patients treated with semi-specific immunoadsorption for primary membranous nephropathy between January 2021 and March 2023. Two patients were anti-PLA2R-autoantibody-positive and one was seronegative. The average age was 59 ± 17 years. Semi-specific immunoadsorption did not reduce albuminuria, but it, nevertheless, led to an increase in serum albumin, contributing to the regression of edema. It effectively eliminated anti-PLA2R autoantibodies in the two anti-PLA2R-positive patients. Consequently, apheresis may not induce a rapid reduction in proteinuria, but could contribute to a more accelerated remission when combined with the anti-CD20 treatment. [ABSTRACT FROM AUTHOR]

Background: Annexin A1 is a membrane‐associated calcium‐binding protein that participates in the progression of many diseases by facilitating vesicle aggregation. It has been documented that reducing vesicle formation alleviates podocyte injury and albuminuria in idiopathic membranous nephropathy (IMN). However, the role of Annexin A1 (ANXA1) in IMN is unknown. Methods: Electron microscopy was used to observe the numbers of vesicles in podocytes. The expression of ANXA1 in IMN was investigated by bioinformatics analysis. We validated the hub genes with the Nephroseq V5 online tool and microarray data from the GEO. Immunohistochemical staining and qPCR were performed to measure gene and protein expression. Results: The numbers of vesicles in IMN podocytes were significantly increased. Bioinformatics analysis showed that ANXA1, one of the differentially expressed genes, was upregulated in glomeruli from IMN patients. In the validation database and dataset, we confirmed that ANXA1 expression was upregulated in the glomeruli of IMN patients. We revealed that the increased expression of ANXA1 was negatively correlated with the glomerular filtration rate (GFR) and proteinuria. Moreover, ANXA1 was enriched in the biological process of vesicle fusion, in which the expression of SNAREs and the SNARE complex was increased. Finally, the expression of ANXA1 and genes related to SNAREs and the SNARE complex was upregulated in glomeruli from IMN patients according to immunohistochemical staining and qPCR. Conclusion: We conclude that ANXA1 may mediate endocytic vesicle fusion and transport by promoting SNARE assembly, contributing to the morphological changes in podocytes and massive proteinuria in IMN. [ABSTRACT FROM AUTHOR]

Objective: To explore role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in idiopathic membranous nephropathy (IMN) and its possible mechanism of activation. Methods: A total of 135 patients with no adrenal corticosteroid and immunosuppressive therapy who were diagnosed with IMN by renal biopsy were collected, and 10 patients with renal tuberculosis and renal tumors who underwent nephrectomy were selected as control group. Immunohistochemical was used to detect NLRP3, tumor necrosis factor receptor-related factor 6 (TRAF6), Caspase-1, NF-κB p65, MAPK signaling pathway-related proteins, including phosphorylated ERK1/2 (p-ERK1/2), phosphorylated p38 (p-p38), phosphorylated JNK (p-JNK) expressions. Blood and 24-hour urine of IMN patients were collected, and 24-hour urine protein quantification, serum creatinine, creatinine clearance rate, blood urea nitrogen and other general clinical data were were analyzed, correlation between urine protein and NLRP3, Caspase-1, IL-1β, TNF- α, NLRP3 and TRAF6 were analyzed, respectively. Results: Compared with control group, 24-hour urine protein and serum creatinine of IMN patients were significantly increased (both P<0.05), and protein expressions of NLRP3 and Caspase-1 in kidney tissues of IMN patients were significantly increased (both P<0.05), among which renal tissue of stage II IMN patients had the highest protein expressions of NLRP3 and Caspase-1, IL-1β and TNF- α expressions were enhanced (both P<0.05), and IL-1β and TNF-α protein expressions in renal tissue of stage II IMN patients were the strongest, protein expressions of NF-κB p65, p-ERK1/2, p-p38 and p-JNK were significantly increased (all P<0.05) . 24-hour urinary protein of IMN patients was positively correlated with expression of NLRP3 protein in kidney tissues (r=0.689, P<0.01), positively correlated with Caspase-1 protein (r=0.614, P<0.000 1), positively correlated with IL-1β (r=0.708, P<0.000 1), positively correlated with TNF-α (r=0.594, P<0.01) . Conclusion: TRAF6 induces ERK1/2, p38 and JNK signaling pathways to stimulate activation of NLRP3 inflammasome through activation of NF-κB, which promotes occurrence of IMN and production of large amounts of urine protein. [ABSTRACT FROM AUTHOR]

Background The effectiveness of multitarget combination therapy with a corticosteroid, cyclosporine and mycophenolate mofetil for idiopathic membranous nephropathy (IMN) is unclear. In the present study, we aimed to compare the efficacy and safety of multitarget therapy with a cyclical corticosteroid–cyclophosphamide regimen in patients with IMN. Methods This was a single-centre, prospective, randomized, controlled trial. We randomly assigned patients with IMN to receive multitarget therapy (a combination of prednisone, cyclosporine and mycophenolate mofetil) or 6-month cyclical treatment with a corticosteroid and cyclophosphamide. The study patients were followed up for 12 months. The primary outcome was a composite of complete or partial remissions at 12 months. Adverse events were also assessed. Results The study cohort comprised 78 patients, 39 of whom received multitarget therapy and the other 39 cyclical alternating treatment with a corticosteroid and cyclophosphamide. At 12 months, 31 of 39 patients (79%) in the multitarget therapy group and 34 of 39 (87%) in the corticosteroid–cyclophosphamide group had achieved complete or partial remissions (relative risk 0.93; 95% confidence interval 0.72–1.21; P  = .85; log-rank test). The prevalence of adverse events was significantly lower in the multitarget therapy group than in the corticosteroid–cyclophosphamide group [46% (18 of 39) vs 74% (29 of 39); P  < .05]. Conclusions Multitarget therapy for IMN patients is noninferior to cyclical alternating treatment with corticosteroid and cyclophosphamide in inducing proteinuria remission and has a better safety profile than the corticosteroid–cyclophosphamide combination. [ABSTRACT FROM AUTHOR]

Background and Purpose: Membranous nephropathy (MN) is an immune‐mediated glomerular disease in adults. Antibody‐ and antigen‐bonding mechanisms have been largely clarified, but the subepithelium immune complex deposition‐mediated downstream molecular mechanisms are currently unresolved. Increasing evidence has suggested that gut microbiota contribute to MN pathogenesis. Experimental Approach: In this study, we identified alterations in faecal gut microbiota and serum metabolites that mediate an aryl hydrocarbon receptor (AhR) mechanism in cationic bovine serum albumin (CBSA)‐induced MN rats and in patients with idiopathic MN (IMN). Key Results: Impaired renal function correlated with the relative abundance of reduced faecal probiotics, Lactobacillus and Bifidobacterium, and altered serum levels of tryptophan‐produced indole derivatives (TPIDs) in MN rats. Further results showed that reduced relative abundance of five probiotics, namely Lactobacillus johnsonii, Lactobacillus murinus, Lactobacillus vaginalis, Lactobacillus reuteri and Bifidobacterium animalis, positively correlated with decreased levels of indole‐3‐pyruvic acid, indole‐3‐aldehyde and tryptamine and negatively correlated with increased levels of indole‐3‐lactic acid and indole‐3‐acetic acid in serum of MN rats. Altered five probiotics and five TPIDs also were observed in patients with IMN. Further studies showed that MN rats exhibited a significant increase in intrarenal mRNA expression of AhR and its target genes CYP1A1, CYP1A2 and CYP1B1, which were accompanied by protein expression of down‐regulated cytoplasmic AhR, but up‐regulated nuclear AhR, in MN rats and IMN patients. Conclusion and Implications: Activation of the intrarenal AhR signalling pathway may involve five TPIDs. These data suggest that gut microbiota could influence MN through TPIDs that engage host receptors. [ABSTRACT FROM AUTHOR]

Serum anti-phospholipase A2 receptor (anti-PLA2R) antibody is used for the noninvasive diagnosis of idiopathic membranous nephropathy (IMN). However, the cutoff value of anti-PLA2R antibodies in IMN patients is debatable. This study aimed to investigate the cutoff value of anti-PLA2R antibodies for diagnosing IMN and the correlation of anti-PLA2R antibodies with clinical parameters and prognosis. A total of 252 IMN patients and 521 non-IMN patients with both renal biopsy and serum anti-PLA2R antibody data from April 2017 to November 2019 were enrolled. Anti-PLA2R antibody was detected by an enzyme-linked immunosorbent assay. The anti-PLA2R antibody titer was higher in the IMN group than in the non-IMN group (153.1 ± 22.4 vs. 2.0 ± 0.2 RU/mL, p < 0.001). The optimal anti-PLA2R antibody cutoff value for diagnosing IMN was 2.5 RU/mL, with a sensitivity, specificity, and Youden index of 85.7%, 88.3%, and 0.740, respectively. There was a significant positive correlation between anti-PLA2R antibody and 24-h urinary protein levels (r = 0.341, p < 0.001), and a significant negative correlation between anti-PLA2R antibody and serum albumin levels (r=-0.274, p < 0.001) in patients with IMN. The remission rates positively correlated with the immunosuppressive usage rates and increased from the low- to the high-titer subgroup. Multivariable Cox regression analysis showed that immunosuppressive therapy (adjusted HR = 4.656; 95% confidence interval [CI], 1.461-14.839; p = 0.009) was associated with a higher remission rate in patients with IMN. The optimal Anti-PLA2R antibody cutoff value for diagnosing IMN was 2.5 RU/mL, which was much lower than that indicated by the manufacturer. If IMN is actively treated, patients can have much better prognoses. [ABSTRACT FROM AUTHOR]

Background: Established prognostic models of idiopathic membranous nephropathy (IMN) were limited to traditional modeling methods and did not comprehensively consider clinical and pathological patient data. Based on the electronic medical record (EMR) system, machine learning (ML) was used to construct a risk prediction model for the prognosis of IMN. Methods: Data from 418 patients with IMN were diagnosed by renal biopsy at the Fifth Clinical Medical College of Shanxi Medical University. Fifty-nine medical features of the patients could be obtained from EMR, and prediction models were established based on five ML algorithms. The area under the curve, recall rate, accuracy, and F1 were used to evaluate and compare the performances of the models. Shapley additive explanation (SHAP) was used to explain the results of the best-performing model. Results: One hundred and seventeen patients (28.0%) with IMN experienced adverse events, 28 of them had compound outcomes (ESRD or double serum creatinine (SCr)), and 89 had relapsed. The gradient boosting machine (LightGBM) model had the best performance, with the highest AUC (0.892 ± 0.052, 95% CI 0.840-0.945), accuracy (0.909 ± 0.016), recall (0.741 ± 0.092), precision (0.906 ± 0.027), and F1 (0.905 ± 0.020). Recursive feature elimination with random forest and SHAP plots based on LightGBM showed that anti-phospholipase A2 receptor (anti-PLA2R), immunohistochemical immunoglobulin G4 (IHC IgG4), D-dimer (D-DIMER), triglyceride (TG), serum albumin (ALB), aspartate transaminase (AST), ß2-microglobulin (BMG), SCr, and fasting plasma glucose (FPG) were important risk factors for the prognosis of IMN. Increased risk of adverse events in IMN patients was correlated with high anti-PLA2R and low IHC IgG4. Conclusions: This study established a risk prediction model for the prognosis of IMN using ML based on clinical and pathological patient data. The LightGBM model may become a tool for personalized management of IMN patients. [ABSTRACT FROM AUTHOR]

Background: Idiopathic membranous nephropathy is widely recognized as an autoimmune kidney disease that is accompanied by the discovery of several autoantibodies, and the antibody subclass in the circulation of patients with iMN is mainly IgG. However, the direct pathogenic effect of the containing anti-PLA2R IgG antibody on podocytes is not clear. Method: A protein G affinity chromatography column was used to purify serum IgG antibodies. Containing anti-PLA2R IgG antibodies from iMN patients and IgG from healthy controls were also obtained. Based on the established in vitro podocyte culture system, purified IgG antibodies from the two groups were used to stimulate podocytes, and the expression of essential podocyte proteins (podocin), the levels of inflammatory cytokines in the cell supernatant, cytoskeletal disorders, and podocyte apoptosis were analyzed. Results: Compared with that in the normal IgG group, the expression of podocin and podocin mRNA was reduced (p = 0.016 and p = 0.005, respectively), the fluorescence intensity of podocin on the surface of podocytes was reduced, the cytoskeleton of podocytes was disordered and reorganized, and the ratio of podocyte apoptosis was increased in the iMN group (p = 0.008). Conclusion: The containing anti-PLA2R IgG antibody might have a direct damaging effect on podocytes in idiopathic membranous nephropathy. [ABSTRACT FROM AUTHOR]

To investigate the effects of glucocorticoid combined with rituximab on blood lipids, helper T cell 17 (Th17)/regulatory T cell (Treg) imbalance, serum anti-phospholipase A2 receptor (PLA2R) antibody and anti-type I thrombospondin 7A domain (THSD7A) antibody in patients with idiopathic membranous nephropathy (IMN). 112 IMN patients who were admitted to Tangdu Hospital of Air Force Military Medical University from March of 2022 to March 2023 were collected. Enrolled patients were divided into control group (56 cases, glucocorticoid treatment) and treatment group (56 cases, rituximab treatment on the basis of control group) according to the random number table method. The efficacy, blood lipids [low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG)], renal function [cystatin C (CysC), serum creatinine (Scr), blood urea nitrogen (BUN), 24 hour urine total protein quanti-fication], Th17/Treg related indicators [Th17 cell percentage, interleukin-17 (IL-17), Treg cell percentage, transforming growth factor β1 (TGF-β1), tumor necrosis factor-α (TNF-α)], serum PLA2R antibody and THSD7A antibody levels were observed in two groups, and the safety in two groups was observed. Compared with control group, the total clinical effective rate in treatment group was higher (P<0.05). Compared with control group, TC, TG, LDL-C, CysC, Scr, BUN, 24 hour urine total protein quanti-fication, Th17, IL-17, TNF-α, PLA2R antibody, THSD7A antibody were lower in treatment group 6 months after treatment, and HDL-C, Treg and TGF-β1 were higher (P<0.05). There was no difference in the incidence of adverse reactions between two groups (P>0.05). Glucocorticoid combined with rituximab in patients with IMN can effectively improve blood lipids, Th17 / Treg imbalance, serum PLA2R antibody and THSD7A antibody levels, without increasing the incidence of adverse reactions, and has good clinical application value. [ABSTRACT FROM AUTHOR]

Idiopathic membranous nephropathy (IMN) is the leading cause of nephrotic syndrome in the elderly. The treatment of idiopathic membranous nephropathy is quite challenging due to the particularity of elderly patients. This study intends to investigate the clinicopathological characteristics and initial therapeutic effect of idiopathic membranous nephropathy among elderly patients. A retrospective study of 67 elderly patients (58.2% male, median age 69.0 years, range, 65–83 years) with biopsy-proven membranous nephropathy was conducted at Guangdong Provincial People's Hospital from 2016 to 2020. Data on clinicopathological characteristics and initial therapeutic effects were analyzed. Of the 67 patients, the mean eGFR of overall patients was 66.49 mL/min/1.73m2 while the median urine protein-to-creatinine ratio (uPCR) and urine albumin-to-creatinine ratio (uACR) was 5676.73 mg/g and 2951.56 mg/g, respectively. Pathological data revealed that the membranous Churg's stage II was the most frequent (71.64%). Moreover, glomerular PLA2R antigen fluorescence intensity of (+) and IgG4 antigen fluorescence intensity of (++) were detected in 63.6% and 86.4% of all patients, respectively. Overall, 44 patients, accounting for 65.7%, achieved remission including complete remission and partial remission within 1 year after renal biopsy. Compared with a non-remission group, the levels of uPCR (6274.6 vs. 3235.6 mg/g, p = 0.007) and uACR (3433.6 vs. 1773.2 mg/g, p = 0.017) were significantly higher in remission group. The proportion of immunosuppressive therapy in the remission group was also higher (86.4% vs. 30.4%, p < 0.01). Compared with conservative treatment, patients with combined treatment with glucocorticoid and cyclophosphamide (CTX) or glucocorticoid and calcineurin inhibitor (CNIs) achieved higher remission rate (glucocorticoid plus cyclophosphamide vs. conservative treatment, 84.6% vs. 27.3%, p = 0.001; glucocorticoid plus calcineurin inhibitor vs. conservative treatment, 88.0% vs. 27.3%, p < 0.001). Further analysis showed that compared with patients who underwent conservative treatment, the proportion of males, the levels of uPCR, uACR, BUN, Scr, CysC and PLA2R antigen-positive staining rate in kidney biopsy were higher in those who underwent combined treatment with glucocorticoid and CTX, while the levels of eGFR, TP and ALB were lower (p < 0.05). In addition, patients who received combined treatment with glucocorticoid and CNIs had higher levels of uPCR, uACR, TC and lower levels of TP, ALB than those who received conservative treatment (p < 0.05). Moreover, there were no statistically significant differences in the 1-year progression rate in eGFR between the immunosuppressive treatment group and conservative treatment group (3.3 vs. 0.2 ml/min/1.73m2, p = 0.852). Most elderly patients diagnosed with IMN had multiple comorbidities, and the membranous Churg's stage II was most common. The glomerular PLA2R and IgG4 antigen deposition were frequently detected accompanied by glomerulosclerosis and severe tubulointerstitial injury. For high-risk elderly patients with severe proteinuria, early initial immunosuppressive therapy could achieve a higher urinary protein remission rate. Therefore, it is crucial for clinicians to balance the risks and benefits of immunosuppressive therapy based on clinical and pathological characteristics and develop individualized treatment regimens for elderly patients with IMN. [ABSTRACT FROM AUTHOR]

Membranous nephropathy (MN) and minimal change disease (MCD) are two common types of nephrotic syndrome that have similar clinical presentations but require different treatment strategies. Currently, the definitive diagnosis for these conditions relies on invasive renal biopsy, which can be limited in clinical practice. In this study, we aimed to differentiate idiopathic MN (IMN) from MCD using clinical data and gut microbiota. We collected clinical data and stool samples from 115 healthy individuals, 115 IMN, and 45 MCD at the onset of disease and performed 16S rRNA sequencing. Through machine learning methods including random forest, logistic regression, and support vector machine, a classifier to differentiate IMN from MCD was constructed. Baseline clinical data comparing the IMN and MCD groups showed that the MCD had higher levels of hemoglobin, uric acid, cystatin C, β2-microglobulin, α1-microglobulin, total cholesterol, and low-density lipoprotein and lower levels of albumin and CD4+ T-cell counts. The gut microbiota of the two groups differed at all levels of the phylum and genus. Differential gut microbiota may disturb the integrity of the intestinal wall and lead to the passage of inflammatory mediators through the intestinal barrier, causing kidney injury. We constructed a noninvasive classifier with a discrimination efficacy of 0.939 that combined the clinical data and gut microbiota information to identify IMN and MCD. The classifier of the gut microbiota combined with clinical indicators has achieved good performance in identifying IMN and MCD, which provides a new approach for the noninvasive discrimination of different pathological types of kidney disease. [ABSTRACT FROM AUTHOR]

To investigate the clinical and kidney pathological features and prognosis of idiopathic membranous nephropathy (IMN) with kidney tubulointerstitial damage (TID). Based on the presence or absence of kidney TID by kidney biopsy, 300 patients diagnosed with IMN were categorized into non-TID (TID−) and tubulointerstitial injury (TID+) groups. The clinical and pathological data were analyzed retrospectively. All patients were followed up for 6–24 months after treatment with glucocorticoids (GCs) combined with cyclophosphamide or GCs combined with calcineurin inhibitors (CNIs) to observe treatment effects on patient prognosis. The patients in the TID + group were older and more likely to be male. The 24-h urine protein, blood urea nitrogen, serum creatinine, cystatin C, β2-microglobulin, and antiphospholipase A2 receptor antibody levels were higher than those in the TID − group and the pathological manifestations were more severe. After 1 year of follow-up, the overall response rate (complete response + partial response) in the TID + group was lower (66.67% vs. 80.89%, p =.022) than in the other. After combined GC and CNI therapy, the complete remission rate in the TID + group was significantly lower than that in the TID − group (13.79% vs. 35.46%, p =.022). The 24-h urine protein level was an independent risk factor for worsening kidney condition (p =.038). Patients with IMN with TID have more severe clinical manifestations and pathological damage and lower remission rates. IMN with TID is a risk factor for worsening kidney condition; however, it is not an independent risk factor. [ABSTRACT FROM AUTHOR]

Idiopathic membranous nephropathy (IMN) is a common type of nephrotic syndrome, and is associated with acute kidney injury (AKI). We investigated the association of multiple variables with AKI in patients with IMN. The data of 187 patients with biopsy-proven IMN were examined. Renal outcome was defined as progression to end-stage renal disease (ESRD). Binary logistic regression and Kaplan–Meier's analysis were used for statistical analysis. During follow-up, 46 (24.6%) patients developed AKI. The incidence of AKI was greater in males than females (p <.01). The AKI group had higher uric acid, lower serum PLA2R antibody positive, and worse baseline kidney function (all p <.01). Most patients in the AKI group had stage I (71.74%) or stage II (21.74%). The AKI group had higher renal tubular injury score and chronicity index (both p <.05). Binary logistic regression indicated that uric acid and baseline estimated glomerular filtration rate (eGFR) were independent risk factors for AKI in patients with IMN (p <.05). The optimal cutoff value of serum uric acid for predicting AKI was 402.50 μmol/L and the baseline eGFR was 96.83 mL/min/1.73 m2. Kaplan–Meier's analysis showed that the cumulative renal survival rate was lower in the AKI group (p =.047). AKI increases the risk of poor prognosis in IMN patients and the high uric acid and low baseline eGFR were considered independent predictors for developing AKI in patients with IMN. [ABSTRACT FROM AUTHOR]

Rituximab (RTX) has been the first option in idiopathic membranous nephropathy (IMN). However, the clinical effect was not very satisfactory. This study aimed to explore the clinical efficacy and safety of the combination of RTX and glucocorticoids (GC) in anti-phospholipase A2 receptor (anti-PLA2R) antibody positive IMN. Sixty-six patients were randomly divided into RTX/GC group (RTX infusion plus short-term oral GC) and RTX group (RTX infusion alone) in this prospective cohort study. Complete remission (CR) and partial remission (PR) were the primary outcomes. Adverse events were the secondary outcomes. The laboratory index including serum albumin, 24 h urinary protein, serum creatinine, estimated glomerular filtration rate, and anti-PLA2R antibody titer were also monitored. All patients were followed for at least 12 months. During the 12-month follow-up, the composite remission rates in RTX/GC and RTX groups were 74.3% and 67.7%, and the CR rates were 34.3% and 19.4%, respectively. The median time of remission in RTX/GC group was shorter than the RTX group (P < 0.001). Compared with RTX monotherapy, the combination of RTX and GC significantly decreased the anti-PLA2R antibody titer (P = 0.028). No significant difference was observed in the incidence of adverse events. The results of the Kaplan–Meier survival analysis indicated that the cumulative CR rate and cumulative composite remission rate in RTX/GC group were all better than the RTX group (P = 0.043, P = 0.040, respectively). The combination of RTX and GC was better than RTX monotherapy without increasing the adverse events in the treatment of IMN. [ABSTRACT FROM AUTHOR]

Background Immunoglobulin A nephropathy (IgAN) and idiopathic membranous nephropathy (IMN) are the most common glomerular diseases. Immunofluorescence (IF) tests of renal tissues are crucial for the diagnosis. We developed a multiple convolutional neural network (CNN)-facilitated diagnostic program to assist the IF diagnosis of IgAN and IMN. Methods The diagnostic program consisted of four parts: a CNN trained as a glomeruli detection module, an IF intensity comparator, dual-CNN (D-CNN) trained as a deposition appearance and location classifier and a post-processing module. A total of 1573 glomerular IF images from 1009 patients with glomerular diseases were used for the training and validation of the diagnostic program. A total of 1610 images of 426 patients from different hospitals were used as test datasets. The performance of the diagnostic program was compared with nephropathologists. Results In >90% of the tested images, the glomerulus location module achieved an intersection over union >0.8. The accuracy of the D-CNN in recognizing irregular granular mesangial deposition and fine granular deposition along the glomerular basement membrane was 96.1% and 93.3%, respectively. As for the diagnostic program, the accuracy, sensitivity and specificity of diagnosing suspected IgAN were 97.6%, 94.4% and 96.0%, respectively. The accuracy, sensitivity and specificity of diagnosing suspected IMN were 91.7%, 88.9% and 95.8%, respectively. The corresponding areas under the curve (AUCs) were 0.983 and 0.935. When tested with images from the outside hospital, the diagnostic program showed stable performance. The AUCs for diagnosing suspected IgAN and IMN were 0.972 and 0.948, respectively. Compared with inexperienced nephropathologists, the program showed better performance. Conclusion The proposed diagnostic program could assist the IF diagnosis of IgAN and IMN. [ABSTRACT FROM AUTHOR]

Membranous nephropathy (MN) patients are diagnosed by the presence of phospholipase A 2 receptor (PLA2R) before they progress to renal failure. However, the subepithelium-like immunocomplex deposit-mediated downstream molecular pathways are poorly understood. The aryl hydrocarbon receptor (AHR), NF-ƙB and Nrf2 pathways play central roles in the pathogenesis and progression of chronic kidney disease. However, their mutual effects on MN require further examination. Thus, we investigated the effect of AHR signalling on the NF-ƙB and Nrf2 pathways in IMN patients, cationic bovine serum albumin (CBSA)-injected rats and zymosan activation serum (ZAS)-treated podocytes. IMN patients show significantly decreased serum total protein and albumin levels, increased urine protein levels and intrarenal IgG 4 and PLA2R protein expression in glomeruli compared with controls. IMN patients exhibited increased mRNA expression of intrarenal AHR and its target genes, including CYP1A1 , CYP1A2 , CYP1B1 and COX-2. This increase was accompanied by significantly upregulated protein expression of CD3, NF-ƙB p65 and COX-2 and significantly downregulated Nrf2 and HO-1 expression. Similarly, CBSA-induced rats showed severe proteinuria and activated intrarenal AHR signalling. This was accompanied by significantly upregulated protein expression of intrarenal p -IκBα, NF-κB p65 and its gene products, including COX-2, MCP-1, iNOS, 12-LOX, p47phox and p67phox, and significantly downregulated protein expression of Nrf2 and its gene products, including HO-1, catalase, GCLC, GCLM, MnSOD and NQO1. These results were further verified in ZAS-induced podocytes. Treatment with the AHR antagonist CH223191 and AHRsiRNA significantly preserved podocyte-specific protein expression and improved the NF-ƙB and Nrf2 pathways in ZAS-induced podocytes. In contrast, similar results were obtained in ZAS-induced podocytes treated with the NF-ƙB inhibitor BAY 11–7082 and NF-κBp65 siRNA. However, neither method had a significant effect on AHR signalling. Collectively, these results indicate that the NF-ƙB pathway is a downstream target of AHR signalling. Our findings suggest that blocking AHR signalling inhibits oxidative stress and inflammation, thereby improving proteinuria and renal injury. [Display omitted] • Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. • Intrarenal AHR, NF-ƙB and Nrf2 pathways were activated in membranous nephropathy patients. • Intrarenal AHR, NF-ƙB and Nrf2 signalling pathways were activated in the CBSA-induced rats. • The AHR, NF-ƙB and Nrf2 signalling pathways were activated in the ZAS-induced podocytes. • Oxidative stress and inflammation could be mediated AHR signalling in podocyte injury. [ABSTRACT FROM AUTHOR]

• Circulating CD19+CD24hiCD38hi B cells are expanded in IMN patients. • The frequency of CD19+CD24hiCD38hi B cells are associated with disease severity in IMN patients. • The percentage of CD19+CD24hiCD38hi B cells was positively associated with Th17 cell frequency in IMN patients. • CD19+CD24hiCD38hi B cells in IMN patients displayed a skewed pro-inflammatory cytokine profile. CD19+CD24hiCD38hi regulatory B cells exert immunosuppressive functions by producing IL-10, but their role in idiopathic membranous nephropathy (IMN) remains elusive. Here, we investigated the frequency and functional changes of circulating CD19+CD24hiCD38hi B cells and evaluated the correlation of CD19+CD24hiCD38hi B cells with clinical features and T helper cell subsets in IMN patients. Compared with healthy controls (HCs), IMN patients showed an increased frequency of CD19+CD24hiCD38hi B cells, but a significant reduction in the percentage of CD19+CD24hiCD38hi B cells was observed 4 weeks after cyclophosphamide treatment. The frequency of CD19+CD24hiCD38hi B cells was positively correlated with the levels of 24h urinary protein, but negatively correlated with serum total protein and serum albumin, respectively. CD19+CD24hiCD38hi B cells in IMN patients displayed a skewed pro-inflammatory cytokine profile with a higher level of IL-6 and IL-12, but a lower concentration of IL-10 than their healthy counterparts. Accompanied by upregulation of Th2 and Th17 cells in IMN patients, the percentage of CD19+CD24hiCD38hi B cell subset was positively associated with Th17 cell frequency. In conclusion, CD19+CD24hiCD38hi B cells were expanded but functionally impaired in IMN patients. Their altered pro-inflammatory cytokine profile may contribute to the pathogenesis of IMN. [ABSTRACT FROM AUTHOR]

This study aimed to explore the clinical efficacy of different treatment regimens for idiopathic membranous nephropathy (IMN). Patients with IMN were retrospectively analyzed by dividing into two groups: glucocorticoids combined with cyclophosphamide group (GC + CYC) and glucocorticoids combined with calcineurin inhibitor group (GC + CNIs). After 1 year of treatment, those who found that the initial treatment was not effective were switched to another regimen. Patients continued to be followed up for at least 1 year to observe the treatment effects of different treatment regimens. This study found that the rate of complete and partial remission (CR + PR) in the GC + CYC and GC + CNIs groups was 76.19 vs. 82.63% after 1 year of follow-up (p >.05). In the GC + CYC and GC + CNIs groups, 27.78 and 11.95% of the patients switched treatment regimens, respectively. After 2 years of follow-up, the CR + PR rate was significantly higher in the change to GC + CNIs group after the switch compared to before the switch (80.00 vs. 31.43%, p <.001). It was also significantly higher in the change to GC + CYC group compared to before the switch (68.42 vs. 31.58%, p =.023). The recurrence rate was significantly higher in the maintain GC + CNIs and change to GC + CNIs groups than in the maintain GC + CYC and change to GC + CYC groups (25.14 vs 6.36%, p <.001). The disengagement rate from immunotherapy was significantly higher in the maintain GC + CYC group and the change to GC + CYC group than in the maintain GC + CNIs group and the change to GC + CNIs group (76.36% vs 29.71%, p <.001). High titer of anti-phospholipase A2 receptor (anti-PLA2R) antibody (95%CI: 0.199–0.947, p =.036) and serum C3 (95%CI: 0.030–0.570, p =.007) were independent risk factors, while serum IgG (95%CI: 1.000–1.331, p =.050) was a favorable factor for achieving CR. Anti-PLA2R antibody was the independent risk factor that affected the worse renal condition (p =.023). Timely change of treatment regimen can significantly enhance therapeutic effect. Compared with patients administered with CYC, those administered with CNIs were less likely to leave treatment and had a higher recurrence rate. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the cost-effectiveness of immunosuppressive therapy for patients with progressive idiopathic membranous nephropathy (IMN) from the Chinese healthcare system perspective. Methods: To estimate the cost-effectiveness of four regimens namely cyclophosphamide, cyclosporine, rituximab and tacrolimus-rituximab in treatment of IMN recommended by the updated Kidney Disease: Improving Global Outcomes (KDIGO) guideline 2021, a Markov model with five discrete states (active disease, remission, dialysis, kidney transplant and death) based on IMN patients aged 50 or above over a 30-years time horizon was constructed. Total costs were imputed from the Chinese healthcare system perspective, and health outcomes were converted into quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) was used to describe the results. The willingness-to-pay (WTP) threshold was set at $12,044 (China's 2021 Gross Domestic Product per capita). Sensitivity analyses were performed to test the uncertainties of the results. Result: Compared with cyclophosphamide, both cyclosporine (incremental cost $28,337.09, incremental QALY-1.63) and tacrolimus-rituximab (incremental cost $28,324.13, incremental QALY -0.46) were considered at strictly dominated for their negative values in QALYs, and the ICER value of rituximab was positive (incremental cost $9,162.19, incremental QALY 0.44). Since the ICER of rituximab exceeds the pre-determined threshold, cyclophosphamide was likely to be the best choice for the treatment of IMN within the acceptable threshold range. The results of the sensitivity analysis revealed that the model outcome was mostly affected by the probability of remission in rituximab. In a probabilistic sensitivity analysis, cyclophosphamide had 62.4% probability of being cost-effective compared with other regimens when the WTP was $12,044 per QALY. When WTP exceeded $18,300, rituximab was more cost-effective than cyclophosphamide. Conclusion: Compared with cyclosporine, rituximab and tacrolimus-rituximab, our model results indicated that cyclophosphamide represented the most cost-effective regimen for patients with progressive IMN in China. [ABSTRACT FROM AUTHOR]

Background: Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor (PLA2R-ab) are considered as diagnostic biomarkers of IMN. Objective: Here, we performed an updated meta-analysis to assess the diagnostic value of PLA2R-ab for clinical remission in IMN patients. Method: PubMed, Embase, and Cochrane databases were searched for relevant studies published before September 2022. Odds ratios and corresponding 95% confidence intervals were determined using a fixed or random effects model. The heterogeneity among studies was explored by subgroup analysis. Results: Sixteen studies involving 1,761 IMN participants were included. There were significant differences between PLA2R-ab (+) and PLA2R-ab (−) patients in terms of complete remission (CR) and spontaneous remission. The rates of partial remission (PR) and relapse were similar between the two groups. Patients with PLA2R-ab (−) were at a higher CR rate when treated with a calcineurin inhibitor or a treatment course for 3 months and 6 months, while the spontaneous remission rate was higher in PLA2R-ab seronegative patients from Asia. However, the CR and spontaneous remission rate only significantly declined in IMN patients with the highest titer, but not a middle titer, when compared to those with the lowest titer. Conclusion: In contrast with previous meta-analyses, our results verified that PLA2R-ab can likely predict CR and spontaneous remission in IMN patients, instead of PR and relapse. Race, immunosuppressive agents, and duration of treatment may affect the prognostic value of PLA2R-ab. Considering that the remission rate of IMN patients with a middle level of PLA2R-ab was not different from that of patients with the lowest level, a proper cut-off value of PLA2R-ab for prognosis should be clarified. [ABSTRACT FROM AUTHOR]

Aims: Idiopathic membranous nephropathy (IMN) is a common cause of adult nephrotic syndrome. Currently, the diagnosis of IMN mainly depends on renal biopsy, which is invasive. What's more, markers already known for the clinical diagnosis of IMN are not sensitive enough. The present study aims to investigate the profiling of urinary exosomal circular RNAs (circRNAs) of IMN, and to look for a potential biomarker for diagnosis of IMN. Methods: Urine exosomes were collected from patients with IMN and idiopathic nephrotic syndrome (INS), as well as healthy controls (HCs) by ultracentrifuge. A pairwise comparison between 5 IMN and 5 HC was performed by high-throughput sequencing. Enrichment analysis were performed to explore the potential functions of differentially expressed circRNAs in IMN. Among three differentially expressed circRNAs which may be involved in signaling pathways of pathogenesis of IMN and matched conserved mouse circRNAs, hsa_circ_0001250 was selected as the target circRNA after quantitative polymerase chain reaction among 23 IMN, 19 INS and 23HC. Sanger sequencing and RNase R digestion assay were performed to validated the ring-structure and sequence of hsa_circ_0001250. ROC (Receiver Operating Characteristic) curve correlation analysis was used to further validate the potential utility of hsa_circ_0001250 as a diagnostic biomarker of IMN. A circRNA-miRNA-mRNA network was constructed to reflect the relationship between hsa_circ_0001250 and its target miRNAs and mRNAs. Results: 766 up-regulated and 283 down-regulated circRNAs were identified in IMN patients. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed signaling pathways of pathogenesis of IMN which the different expressed circRNAs may participate in. The ring-structure and the sequence of hsa_circ_0001250 were confirmed, the expression of hsa_circ_0001250 was validated significantly increased in IMN, relevant with high level of proteinuria. A circRNA-miRNA-mRNA network reflected that hsa_circ_0001250 may play a role in the pathogenesis of IMN by target hsa-miR-639 and hsa-miR-4449. Conclusion: We revealed the expression and functional profile of differentially expressed urinary exosomal circRNAs of IMN patients. Urinary exosomal hsa_circ_0001250 was tested as a potential biomarker of IMN and a predicted circRNA-miRNA-mRNA network was constructed. [ABSTRACT FROM AUTHOR]

Primary glomerular disease was the leading cause of chronic kidney disease (CKD) in China; however, changes in the economy and environment introduce variations in the spectrum of kidney diseases. This study aimed to analyze renal biopsy data to inform disease prevention and public health interventions. In this retrospective cohort study, data from 2,803 consecutive renal biopsies conducted at our center between January 2010 and December 2018 were analyzed. The sample was disaggregated by age and the date of biopsy to facilitate analysis. Primary glomerulonephritis (PGN) is the most frequent (81.84%) finding, followed by secondary glomerulonephritis (SGN; 15.38%), tubulointerstitial nephritis (15.38%), and others (1.57%). IgA nephropathy (IgAN), idiopathic membranous nephropathy (iMN), and minimal change disease were the primary causes of PGN. Among PGN cases, the incidence of iMN arose, especially among those aged ≥ 60 years old, during the observation period. Contrary to the case of iMN, the proportion of IgAN in PGN trended downward, continuously, and at length. Moreover, IgAN mainly affected those aged 25–44 years old and less so those aged ≥ 60 years old. Lupus nephritis, Henoch–Schönlein purpura nephritis, and diabetic nephropathy (DN) were key causes of SGN. A ratio reversal between infectious disease and chronic disease dramatically changed SGN patterns. In the past year, the incidence of hepatitis B–related nephritis has constantly declined; however, the proportion of DN among SGN had steadily increased. The incidence of iMN significantly increased during these years. Among SGN cases, the proportion of DN has increased. [ABSTRACT FROM AUTHOR]

Idiopathic membranous nephropathy (iMN) is a major cause of nephrotic syndrome. Atypical membranous nephropathy (aMN) is a new type of nephropathy in China, characterized by a 'full-house' on immunofluorescent examination, that is IgG, IgA, IgM, C3, C1q positive, but without clinical evidence of a secondary cause. Phospholipase A2 receptor (PLA2R) was the major target antigens in iMN patients. Activation of the mannose-binding lectin (MBL) pathway plays a vital role in the development of MN. Our objective was to investigate the role of PLA2R and MBL in the pathogenesis of iMN and aMN. We conducted a retrospective observational study using propensity score matching by age, gender, and eGFR. All clinical, laboratory data, and follow-up data of the patients were collected. Serum levels of anti-PLA2R antibodies and MBL were tested. Finally, 30 iMN patients and 30 aMN patients were included, and 20 healthy controls were retrospectively collected in this study. The 24 h proteinuria level was higher and serum albumin was lower in anti-PLA2R (+) patients than in anti-PLA2R (−) patients in both iMN and aMN groups. In aMN patients, MBL levels were significantly higher in anti-PLA2R (+) patients than in anti-PLA2R (−) patients (p =.045). The serum level of anti-PLA2R positively correlated with no-remission in both iMN and aMN groups. The complement lectin pathway has an association with the development of MN, especially in patients with positive anti-PLA2R antibodies. Serum MBL cannot differentiate between the two diseases. Serum MBL levels are not associated with clinical manifestations, nor with prognosis. [ABSTRACT FROM AUTHOR]

Although thunder god vine (Tripterygium wilfordii) has been widely used for treatment of idiopathic membranous nephropathy (IMN), the pharmacological mechanisms underlying its effects are still unclear. This study investigated potential therapeutic targets and the pharmacological mechanism of T. wilfordii for the treatment of IMN based on network pharmacology. Active components of T. wilfordii were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. IMN-associated target genes were collected from the GeneCards, DisGeNET, and OMIM databases. VENNY 2.1 was used to identify the overlapping genes between active compounds of T. wilfordii and IMN target genes. The STRING database and Cytoscape 3.7.2 software were used to analyze interactions among overlapping genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the targets were performed using Rx64 4.0.2 software, colorspace, stringi, DOSE, clusterProfiler, and enrichplot packages. A total of 153 compound-related genes and 1485 IMN-related genes were obtained, and 45 core genes that overlapped between both categories were identified. The protein–protein interaction network and MCODE results indicated that the targets TP53, MAPK8, MAPK14, STAT3, IFNG, ICAM1, IL4, TGFB1, PPARG, and MMP1 play important roles in the treatment of T. wilfordii on IMN. Enrichment analysis showed that the main pathways of targets were the AGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. This study revealed potential multi-component and multi-target mechanisms of T. wilfordii for the treatment of IMN based on network pharmacological, and provided a scientific basis for further experimental studies. [ABSTRACT FROM AUTHOR]

Glomerular IgM deposition is commonly shown in idiopathic membranous nephropathy, but the clinicopathological features and outcomes of IMN with IgM deposition are unclear. This single-center prospective cohort study enrolled 210 patients with biopsy-proven IMN from January 2016 to December 2018. Clinicopathological features, treatment responses, and kidney outcomes were compared between patients with and without IgM deposition. In total, 76 (36.2%) patients show glomerular IgM deposition. Patients with IgM deposition were younger (45 ± 13.30 vs. 50.59 ± 13.65 years, P = 0.006), had a higher estimated glomerular filtration rate (eGFR) (100.03 [81.31–111.37] vs. 92.67 [74.71–106.63] mL/min/1.73 m2, P = 0.041), and had a lower proportion of nephrotic syndrome (60.5% vs. 75.4%, P = 0.024) at the time of kidney biopsy. Patients with IgM deposition had a significantly higher proportion of focal segmental glomerular sclerosis (FSGS) lesions (27.6% vs. 13.4%, P = 0.011) and C1q deposition (72.4% vs. 57.5%, P = 0.032). Although the treatments and initial treatment responses were comparable, patients with glomerular IgM deposition had a significantly greater proportion of eGFR decline of ≥ 5 mL/min/1.73 m2 per year (log-rank test, P < 0.001) and eGFR decrease of ≥ 10% from baseline (log-rank test, P = 0.003). Cox regression analysis showed that IgM deposition was an independent risk factor of eGFR decline of ≥ 5 mL/min/1.73 m2 per year (HR, 2.442; 95% CI, 1.550–3.848, P < 0.001) and eGFR decline by ≥ 10% from baseline (HR, 2.629; 95% CI, 1.578–4.385, P < 0.001) during follow-up. IgM deposition in the glomeruli is an independent risk factor for decreased renal function in patients with IMN. [ABSTRACT FROM AUTHOR]

Objective To explore the diagnostic value of albumins(ALB), age, chlorine(Cl) and creatinine( Cr)in the diagnosis of idiopathic membranous nephropathy(IMN). Methods Biochemical indexes of 42 patients with IMN and 93 patients with other nephropathy were measured, clinical information was collected, parameters with statistical differences were screened out by AUC, diagnostic model was established by binary logistic regression, and diagnostic value was evaluated by ROC curve. Results There were 10 parameters with statistical difference(P <0.01)in AUC. Through collinearity analysis, after eliminating redundant information parameters, ALB, age, Cl and Cr were retained, and then logistic regression model was constructed. ROC curve analysis showed that AUC of the model was 0.879, Youden index J at the best cutoff point was 0.591 4, sensitivity was 66.67%, specificity was 92.47%, and the standard of auxiliary diagnosis model (PRE) was 0.544 3, meaning if PRE>0.544 3, then it was determined as IMN patients, otherwise it was other kidney disease patients. Conclusion The combination of ALB, age, Cl and Cr has certain reference value for the auxiliary diagnosis of IMN. [ABSTRACT FROM AUTHOR]

The therapeutic effects of tacrolimus (TAC) versus cyclophosphamide (CTX) were not fully illustrated for patients with idiopathic membranous nephropathy (IMN). The PubMed, EmBase, Cochrane library, and CNKI were systematically searched throughout March 2020 for randomized controlled trials evaluating the therapeutic effects of TAC versus CTX for IMN patients treated with steroids. The pooled relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using the random-effects model. Twelve trials recruited a total of 868 IMN patients were identified and contained in final meta-analysis. Patients in TAC group was associated with an increased incidence of overall remission (12 trials: 868 patients; RR: 1.21; 95% CI: 1.11–1.31; p < 0.001) and complete remission (12 trials: 868 patients; RR: 1.50; 95% CI: 1.25–1.80; p < 0.001). Moreover, we noted TAC therapy significantly reduced urinary protein excretion (9 trials: 567 patients; WMD: −1.06; 95%CI: −1.41 to −0.71; p < 0.001), and increased serum albumin (9 trials: 567 patients; WMD: 5.37; 95%CI: 2.97 to 7.77; p < 0.001) than CTX therapy. Furthermore, no significant difference between TAC and CTX for serum creatinine was detected (6 trials: 378 patients; WMD: 0.15; 95%CI: −3.46 to 3.75; p = 0.936). Finally, the risk of alopecia (p = 0.008), infection (p = 0.045), leukocytosis (p = 0.002), and elevated ALT/AST (p = 0.011) in TAC group was significantly lower than CTX group, whereas TAC was associated with an increased risk of tremor than CTX (p = 0.010). This study found IMN patients treated with TAC combined with steroids provides a better therapeutic effect and less adverse events than those treated with CTX combined with steroids, with moderate-certainty evidence. [ABSTRACT FROM AUTHOR]

Background: Idiopathic membranous nephropathy (IMN) is a cause of nephrotic syndrome that is increasing in incidence but has unclear pathogenesis. Urinary peptidomics is a promising technology for elucidating molecular mechanisms underlying diseases. Dysregulation of the proteolytic system is implicated in various diseases. Here, we aimed to conduct urinary peptidomics to identify IMN-related proteases. Results: Peptide fingerprints indicated differences in naturally produced urinary peptide components among 20 healthy individuals, 22 patients with IMN, and 15 patients with other kidney diseases. In total, 1,080 peptide-matched proteins were identified, 279 proteins differentially expressed in the urine of IMN patients were screened, and 32 proteases were predicted; 55 of the matched proteins were also differentially expressed in the kidney tissues of IMN patients, and these were mainly involved in the regulation of proteasome-, lysosome-, and actin cytoskeleton-related signaling pathways. The 32 predicted proteases showed abnormal expression in the glomeruli of IMN patients based on Gene Expression Omnibus databases. Western blot revealed abnormal expression of calpain, matrix metalloproteinase 14, and cathepsin S in kidney tissues of patients with IMN. Conclusions: This work shown the calpain/matrix metalloproteinase/cathepsin axis might be dysregulated in IMN. Our study is the first to systematically explore the role of proteases in IMN by urinary peptidomics, which are expected to facilitate discovery of better biomarkers for IMN. [ABSTRACT FROM AUTHOR]

• We established a dual-labeled PLA2R-IgG4/IgG-TRFIA for simultaneous detection. • Accurate diagnosis of IMN could be achieved using the anti-PLA2R-IgG4/IgG ratio. • Anti-PLA2R-IgG/IgG4 TRFIA contributes to the accurate diagnosis of IMN. • Combined detection approach increases the positive rate of IMN from 86.5 % to 91.7 %. • The false-positive rates of other diseases decreased from 25 to 50 % to 0 %. The renal biopsy is an accurate and reliable gold standard for membranous nephropathy (MN) diagnosis. However, it is an invasive procedure involving the risk of hemorrhage or infection. Thus, an alternative approach that can facilitate the effective diagnosis and treatment monitoring of idiopathic membranous nephropathy (IMN) is urgently needed. We established a dual-labeled time-resolved fluoroimmunoassay (TRFIA) to simultaneously detect phospholipase A2 receptor (PLA2R)-IgG4 and PLA2R-IgG antibodies. Utilizing this assay, we determined the ratio of autoantibodies in the serum of patients with different kidney diseases and normal controls. The sensitivity of TRFIA for detecting anti-PLA2R-IgG and anti-PLA2R-IgG4 was 0.12 µg/mL and 0.001 µg/mL, respectively. Human IgA did not interfere with the assay. Compared to anti-PLA2R-IgG alone, the positive rate of IMN could be increased from 86.5 % to 91.7 % through the combined use of anti-PLA2R-IgG4 and the PLA2R-IgG4/IgG ratio. In contrast, the false-positive rates for the detection of IgA nephropathy, lupus nephropathy, diabetic nephropathy, and minimal change nephropathy decreased from 25 to 50 % to 0 %. The dual-labeled PLA2R-IgG4/IgG-TRFIA for simultaneous detection of anti-PLA2R-IgG4 and anti-PLA2R-IgG will contribute to improved accuracy of IMN diagnosis. [ABSTRACT FROM AUTHOR]

Background: Idiopathic membranous nephropathy (IMN) may have various clinical outcomes. Hyperlipidemia is quite common in IMN. However, the utility of the lipid profile in predicting outcomes remains unknown. This study aimed to explore the correlation between hyperlipidemia and proteinuria remission in IMN. Methods: 256 patients who diagnosed with IMN confirmed by renal biopsy in Wuhan Tongji Hospital from January 2016 to October 2020 were included in this study. The end point was defined as a combination of partial and complete remission. Cox proportional-hazards regression analysis and Kaplan–Meier curve were applied to assess the prognostic value of the lipid profile for proteinuria remission. Results: A total of 153 (59.8%) patients achieved remission and 103 (40.2%) did not. The levels of total cholesterol, low-density lipoprotein, and non-high-density lipoprotein were significantly lower in the remission group than in the non-remission group. Non-high-density lipoprotein level revealed the strongest correlation with proteinuria (Spearman's rho = 0.42; P < 0.001). The multivariate analysis demonstrated that serum total cholesterol [hazard ratio (HR): 0.883; 95% confidence interval (CI): 0.813–0.958; P = 0.003] and non-high-density lipoprotein cholesterol (HR: 0.892; 95% CI: 0.820–0.970; P = 0.007) levels were independent markers to predict proteinuria remission in IMN. Conclusions: Among the lipid profile, the non-high-density lipoprotein level exhibited the strongest correlation with proteinuria in IMN. Moreover, elevated serum cholesterol and non-high-density lipoprotein cholesterol concentrations at baseline predicted probability of proteinuria non-remission in IMN. [ABSTRACT FROM AUTHOR]

• The data of B-cell subsets in adult patients with active idiopathic membranous nephropathy (MN) remain limit. • The percentage of CD38high plasmablasts was significantly correlated with disease activity and prognosis in MN. • The percentage of CD38high plasmablasts may serve as a potential biomarker for MN. • Monitoring B-cell subsets dynamics is valuable for the management of idiopathic MN. Idiopathic membranous nephropathy (MN) is an autoimmune disease characterized by specific antibodies. However, the underlying mechanisms by which lymphocytes promote the development of MN remain poorly understood. This study aims to determine the changes of B-cell subsets and their clinical significance in MN patients. We included a cohort of 21 idiopathic MN patients with new onset or a relapse, 19 healthy controls (HCs) and 10 patients with minimal change disease (MCD). Immunohistochemistry and flow cytometry were performed to assess the B-cell infiltration in renal biopsy tissues and peripheral blood, respectively. Idiopathic MN patients (including new-onset and relapse groups) had lower percentages of marginal-zone B (MZB) and non-switched memory B cells, and higher percentages of plasmablasts than HCs (P < 0.01). Particularly, the new-onset group had lower percentages of switched memory B cells and MZB cells, and higher percentages of Naïve B cells than HCs (P <0.05). Interestingly, the percentage of plasmablasts was significantly correlated with urine protein to creatinine ratio, serum albumin, IgG, anti-M-type phospholipase A2 receptor antibody level and age in MN patients (P < 0.05). MN with Ehrenreich-Churg stage Ⅱ-Ⅳ had a lower median percentage of MZB and non-switched memory B cells, while a higher median percentage of plasmablasts than those in MN patients with stage Ehrenreich-Churg I (P < 0.05). Idiopathic MN patients had specific changes in B-cell subsets proportions in peripheral blood. Further studies are needed to precisely determine the roles of B-cell subsets in MN. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical and pathological value of peripheral blood Neutrophil-to-Lymphocyte Ratio (NLR) in idiopathic membranous nephropathy (IMN). Methods: 221 patients with IMN diagnosed from January 2017 to December 2019 were selected as IMN group, and 87 healthy people with normal urine routine and renal function indexes from July 2019 to September 2019 were selected as the normal control group. The NLR value of each research object was calculated, and the difference of NLR value between the two groups was compared. The blood biochemical indexes, renal pathological stage and fibrosis degree of IMN patients were recorded, and glomerular filtration rate (eGFR) was calculated according to MDRD formula, and the correlation between NLR and blood biochemical indexes and pathological characteristics of IMN patients was analyzed.ROC curve was used to analyze the sensitivity and specificity of NLR in evaluating renal interstitial fibrosis of IMN patients. Results: The NLR value of peripheral blood in IMN group was higher than that in control group (P<0.05). Peripheral blood NLR was associated with age and renal interstitial fibrosis (all P<0.05), but not with gender and renal pathological stage (all P>0.05). The value of NLR in peripheral blood of IMN was positively correlated with hs-CRP, SCr and BUN (P<0.05), and negatively correlated with eGFR (P<0.05), but no correlation with ESR, UA, TP, Alb and 24 h urine protein quantification(P>0.05). The NLR values of peripheral blood of IMN patients with different degrees of renal interstitial fibrosis were different, the difference was statistically significant (P<0.05), and the degree of renal interstitial fibrosis in Grade 1, 2, 3, the more serious the degree of fibrosis, the greater the NLR value; the differences were statistically significant between the three levels of IMN (all P<0.05). The area under ROC curve was 0.715 [95% CI (0.626, 0.803)], and the sensitivity and specificity were 68.6% and 66.7% respectively when the cut-off value was 1.858. Conclusion: Peripheral blood NLR can be used as an effective index to evaluate renal function in IMN patients, and it is related to renal interstitial fibrosis in patients with IMN. [ABSTRACT FROM AUTHOR]

The early prediction of renal outcomes in patients with idiopathic membranous nephropathy (iMN) remains challenging. The present retrospective study evaluated patients with iMN confirmed by renal biopsy. An optimized Cox regression model and a nomogram were constructed for the early prediction of renal outcomes. A total of 141 patients who met the inclusion criteria were evaluated in the present study. In total 18 (12.8%) patients eventually progressed to the endpoint, 6 of whom developed end-stage renal disease, and one patient died during follow-up. The optimized model demonstrated that 24-h proteinuria [hazard ratio (HR) 1.24; 95% CI, 1.10-1.40; P-value <0.001] and chronic tubulointerstitial injury [referred to as grade 0, grade 1 (HR), 5.12; 95% CI, 1.33-19.75; P-value=0.02] or grade 2 (HR, 6.43; 95% CI, 1.35-30.59; P-value=0.02) were independent risk factors for a poor renal outcome. Patients with an estimated three-year renal survival rate (ETR) less than 0.87 had a high risk of a poor renal outcome. In addition, patients with an ETR of 0.87 to 0.98 more quickly developed a decreased estimated glomerular filtration rate after two years of follow-up. In the present study a nomogram for the early prediction of renal outcomes in patients with iMN was developed. This nonogram suggested that patients with an ETR of 0.87-0.98 should receive greater attention during follow-up. [ABSTRACT FROM AUTHOR]

Objective: Co-deposition of mannose-binding lectin (MBL) and IgG4 anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies under subepithelial cells has been observed in patients with idiopathic membranous nephropathy (iMN), but the relationships of MBL deposition to iMN severity and progression remain unclear. Methods: Patients diagnosed with iMN who underwent renal puncture were enrolled and followed up for a median of 17 months (interquartile range [IQR], 9–25 months). Serum anti-PLA2R and anti-thrombospondin type-1 domain-containing 7A antibodies and MBL were detected by ELISA. Glomerular MBL and anti-PLA2R antibodies were detected by immunofluorescence. Proteinuria remission, including complete remission (CR), was defined as a clinical event. Clinicopathological characteristics and kidney outcomes were compared between patients with and without MBL deposition. Results: In 67 prevalent patients with biopsy-proven iMN, serum anti-PLA2R antibodies and anti-THSD7A antibodies were present in 37 (55.3%) and 1 (1.4%) patient with iMN. The positivity of glomerular MBL deposition and tissue anti-PLA2R antibody was 53 (79.1%) and 49 (73.1%), respectively. No significant difference was found between the MBL-positive and negative groups in the albumin level (26.5 ± 6.6 and 28.6 ± 6.1 g/L), eGFR (104.8 ± 17.4 and 114.6 ± 16.1 mL/min/1.73 m2), 24-h proteinuria (5.35 and 4.25 g/day), or serum MBL level corrected by serum Cr 4.92 (IQR, 0.86, 8.90) and 2.28 (IQR, 0.4, 5.62). In a Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure, eGFR, immunosuppressive agent use, 24-h proteinuria, and anti-PLA2R antibody concentration, glomerular MBL deposition was independently associated with ICR of proteinuria (HR, 6.31; 95% CI, 1.1–36.1; p = 0.039). Conclusions: The MBL pathway of complement activation is commonly initiated in patients with iMN, and patients with MBL deposition reach ICR faster than patients without MBL deposition. [ABSTRACT FROM AUTHOR]

Objectives: To explore the efficacy and safety of mycophenolate mofetil (MMF) combined with prednisone (Pre) in the treatment of adult idiopathic membranous nephropathy (IMN). Methods: A total of 102 patients with IMN admitted to our hospital from June 2015 to June 2017 were enrolled as the study subjects. The patients were divided into control group and observation group according to the random number table method, with 51 cases in each group. Control group was given Pre while observation group was treated with MMF+Pre, and they were treated for 12 months. The efficacy after 12 months of treatment, and renal function-related indicators [24 h urine protein quantitation (24 h UP), serum cystatin C (CysC), serum urea nitrogen ( BUN), serum creatinine (Scr), serum albumin (Alb)] and lipid metabolism indexes [total cholesterol (TC), triglyceride (TG)] before treatment and at 6 months and 12 months after treatment were compared between the two groups, and the adverse drug reactions during medicine were recorded. Results: After 12 months of treatment, the total effective rate in study group was significantly higher than that in control group (90.20% vs 74.51%) (P<0.05). After 6 months and 12 months of treatment, the levels of 24 h UP, CysC, TC and TG in the two groups were decreased significantly in turn compared with those before treatment while the level of Alb was increased significantly (P<0.05), and the above indicators in observation group were significantly different from those in control group at the same time point (P<0.05). The levels of BUN and Scr in the two groups were not significantly different from those before treatment(P>0.05), and there were no significant differences between the two groups (P>0.05). During treatment, the adverse drug reaction rate in observation group was significantly lower than that in control group (11.76% vs 27.45%)(P<0.05). Conclusions: MMF combined with prednisone has better efficacy in the treatment of adult IMN, and it can significantly improve the renal function and promote the lipid metabolism of patients, and the drug regimen has high safety and high application value. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of losartan potassium on serum phospholipase A2 receptor (PLA2R) antibody in patients with idiopathic membranous nephropathy. Methods: From August 2014 to August 2018, 78 patients with idiopathic membranous nephropathy who were diagnosed and treated in the Department of Nephrology, Hanzhong 3201 Hospital of Xi'an Jiaotong University School of Medicine were equally divided into the observation group and control group accorded to the random number table. The control group was given conventional peritoneum dialysis treatment, and the observation group was treated with losartan potassium on the basis of the control group, and the two groups were treated for 3 months, and the serum anti-PLA2R antibody expression was recorded. Results: The total effective rates of the observation group was 100.0%, which was significantly higher than that of the control group (87.2%)(P<0.05). The BUN, CREA and UA values of the two groups after treatment were lower than those before treatment, and the observation group was also significantly lower than the control group (P<0.05). The levels of serum GSH-PX and SOD values of the two groups after treatment were higher than those before treatment, and the MDA values were lower than before treatment, and the changes in the observation group were more significant (P<0.05). The serum anti-PLA2R antibody expression levels in the two groups after treatment were significantly lower than that before treatment, and the observation group were also significantly lower than the control group (P<0.05). Conclusion: Losartan potassium treatment of idiopathic membranous nephropathy can inhibit the expression of anti-PLA2R antibody and regulate oxidative stress, there by promote the improvement of renal function and improving the therapeutic effect of patients. [ABSTRACT FROM AUTHOR]

Idiopathic membranous nephropathy (IMN) is one of the main types of chronic kidney disease in adults and one of the most common causes of end-stage renal disease. In recent years, the morbidity of IMN among primary glomerular diseases has markedly increased, while the pathogenesis of the disease remains unclear. To address this, a number of experimental models, including Heymann nephritis, anti-thrombospondin type-1 domain-containing 7A antibody-induced IMN, cationic bovine serum albumin, anti-human podocyte antibodies and zymosan-activated serum-induced C5b-9, have been established. This review comprehensively summarized the available animal and cell models for IMN. The limitations and advantages of the current models were discussed and two improved models were introduced to facilitate the selection of an appropriate model for further studies on IMN. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend classical combined therapy of steroid and cyclophosphamide (CYC) for patients with idiopathic membranous nephropathy (IMN), while it is associated with severe adverse effects. Aims: We conducted an observational and retrospective study to evaluate the effectiveness and safety of steroids plus tacrolimus (TAC) versus steroids plus CYC for IMN. Methods: A total of 203 kidney‐biopsy‐proven IMN patients was enrolled in this study. One group (n = 142) received steroid combined with intravenous CYC (750 mg/m2 body surface) and the other group (n = 61) received steroid combined with oral TAC (target blood concentration of 4–8 ng/mL). The primary outcomes were achievement of remission. The secondary end‐points included incidence of adverse events, relapse rates, 24 h urinary protein (UP), serum albumin, serum creatinine and estimated glomerular filtration rate. Results: Over the 18‐month observation period, the study suggested that the remission rates at the first 3 months were significantly higher in TAC group than in CYC group (72.1% vs 54.9%, P < 0.05). Although the cumulative incidence of serious and non‐serious adverse events was not different significantly between the two groups, the incidence after first 3 months was lower in TAC group. Levels of 24‐h UP and serum albumin improved in the TAC group more than in the CYC group (P < 0.05) over the observed period. Conclusions: Because of its short‐term effectiveness and long‐term safety profile, steroid plus TAC might be a better option for IMN. [ABSTRACT FROM AUTHOR]

The present study analyzed the clinicopathological features and prognosis in patients with idiopathic membranous nephropathy (IMN) with hypertension. In the hypertension group, significant differences were found in the age, hypertension history, systolic blood pressure, diastolic blood pressure (DBP), mean arterial pressure, albumin, serum creatinine, low-density lipoprotein, 24 h urine protein levels, calculated estimated glomerular filtration rate (e-GFR), glomerular sclerosis, segmental sclerosis, ischemic sclerosis, interstitial fibrosis, tubular atrophy and vascular lesion compared with the non-hypertension group (P<0.05). The average follow-up time was 35.70 months (5.10-103.77 months). In total, 54 patients reported a 50% decline in e-GFR, eight patients reported progression of disease to end-stage renal disease (ESRD) and nine cases of mortality were reported. Survival analysis results suggested that patients with hypertension had a lower cumulative renal survival rate than those without hypertension (P=0.034). Multivariate Cox hazards regression analysis results suggested that DBP [hazard ratio (H), 5.160; CI, 0.865-0.989; P=0.023], age (H, 4.839; CI, 1.008-1.142; P=0.028), sex (H, 5.680; CI, 0.031-0.714; P=0.017), serum creatinine (H, 20.920; CI, 1.035-1.089; P<0.001), uric acid (H, 4.783; CI, 0.982-0.0.999; P=0.029), 24 h urine protein (H, 6.318; CI, 1.079-1.850; P=0.012), e-GFR (H, 4.008; CI, 1.001-1.062; P=0.045) and glomerular sclerosis (H, 8.722; CI, 1.860-21.559; P=0.003), segmental sclerosis (H, 7.737; CI, 7.770-13.219; P=0.005), percentage of ischemic sclerosis (H, 4.729; CI, 1.444-11.945; P=0.030), crescents (H, 5.938; CI, 0.003-0.526; P=0.015), interstitial fibrosis and tubular atrophy (H, 8.128; CI, 0.005-1.052; P=0.043), and vascular lesion (H, 4.049; CI, 1.030-9.766; P=0.044) were risk factors for the development of IMN into ESRD. The results suggested that DBP may be an independent risk factor for the development of IMN with hypertension. [ABSTRACT FROM AUTHOR]

Membranous nephropathy is one of the most common causes of nephrotic syndrome in the adult population. According to the underlying etiology, membranous nephropathy is classified as either primary or secondary. Systemic lupus erythematosus is an autoimmune disease that can affect the kidneys in 50% of patients in the course of the disease. Renal disease may be the first manifestation of systemic lupus erythematosus and the development of systemic findings may be delayed for about 1–5 years following the diagnosis of lupus nephritis. We present a 59-year-old male patient who had a diagnosis of idiopathic membranous nephropathy since 2007 and developed membranous lupus nephritis during the 12-year follow-up without any extrarenal systemic lupus erythematosus findings. [ABSTRACT FROM AUTHOR]

• Anti-PLA2R antibodies had a good diagnostic performance for IMN in the population with DKD. • A cut-off-value of 2.71 for anti-PLA2R antibodies is more reliable for diagnosing IMN in DKD in China. Serum anti-phospholipase A2 receptor (anti-PLA2R) antibodies are highly accurate in diagnosing idiopathic membranous nephropathy (IMN) in populations with kidney disease. However, the diagnostic value of anti-PLA2R antibodies for IMN in diabetic kidney disease (DKD) is unclear. The objective of this study is to determine the diagnostic efficacy and the optimal cut-off value of this marker in populations with DKD. This study included 227 patients with type 2 diabetes who were admitted to the Department of Nephrology of the Chinese People's Liberation Army General Hospital from May 2016 to January 2018 and underwent pathological diagnosis by renal biopsy. Anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay in this population. According to the pathological results, the participants were divided into an IMN group and non-membranous nephropathy (non-MN) group. The clinical characteristics were analyzed, the diagnostic ability of anti-PLA2R antibodies was evaluated, and the receiver operating characteristic (ROC) curve was constructed to obtain the optimal cut-off value. There were 45 patients in the IMN group, accounting for 19.8% of the study sample. The patients in this group were older at the time of renal biopsy than the non-MN group and presented a shorter duration of diabetes, better glycemic control, lower blood pressure and uric acid, and better renal function; in addition, their clinical symptoms indicated nephrotic syndrome. The optimal cut-off value for anti-PLA2R antibodies for the diagnosis of IMN in DKD was 2.71 Ru/ml, sensitivity was 0.800, specificity was 0.951, positive predictive value was 0.800, negative predictive value was 0.951, accuracy was 0.921, and the Yoden index was 0.750. The area under the ROC curve was 0.87 (95% CI, 0.788–0.952) (p < 0.001). Patients in the IMN group were older, had better renal function and general condition, and the clinical symptoms indicated nephrotic syndrome. Anti-PLA2R antibodies had a good diagnostic performance for IMN in the population with DKD, and the optimal cut-off value was 2.71. [ABSTRACT FROM AUTHOR]