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Objective High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear.Methods Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression.Results Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6–72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405–0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202–0.648; p

Background Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN.Methods A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed.Results Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value.Conclusion Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.

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]

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]

AbstractObjectives 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.Methods 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.Results 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.Conclusions 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.

AbstractBackground 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.Methods 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.Results 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

AbstractBackground To investigate the clinical and kidney pathological features and prognosis of idiopathic membranous nephropathy (IMN) with kidney tubulointerstitial damage (TID).Methods 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.Results 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).Conclusion 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.

AbstractAim 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.Methods 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.Results During follow-up, 46 (24.6%) patients developed AKI. The incidence of AKI was greater in males than females (p

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.

Background 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. Methods 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. Results 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. Conclusion 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.

Objectives 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.Methods 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.Results 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.Conclusions 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.

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]

Background: Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN., Methods: A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed., Results: Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value., Conclusion: Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.

Objective: High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear., Methods: Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression., Results: Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6-72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405-0.927; p  = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202-0.648; p  < 0.001)., Conclusions: A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.

Background The therapeutic effects of tacrolimus (TAC) versus cyclophosphamide (CTX) were not fully illustrated for patients with idiopathic membranous nephropathy (IMN). Methods 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. Results 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

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: This investigation was managed to explore whether miR-193a in combination with two podocytes, namely, Wilms tumor type 1 (WT1) and podocalyxin (PODXL), were feasible in estimating onset and prognosis of idiopathic membranous nephropathy (IMN). Methods: We recruited a total of 189 healthy controls and 364 IMN patients, whose urine samples were prepared to measure the expression of miR-193a and PODXL. Meanwhile, renal tissues collected from above-mentioned IMN patients (n = 364) and renal cell carcinoma patients (n = 189) were arranged to determine the expression of WT1. Ultimately, receiver operating characteristic curves were constructed to appraise the performance of miR-193a, WT1, and PODXL in predicting renal survival of IMN patients. Results: The IMN patients were measured with up-regulated miR-193a expression and down-regulated WT1/PODXL expression, when compared with healthy controls (p 3.79 g/24 h)/serum creatinine (>174.63 μmol/L), and declined GFR (≤68.13 mL/min/1.73 m2) were implicated as prominent biomarkers for the poor renal survival of IMN patients (all p

Objectives: This study aimed to investigate the unique prognostic, clinical, and renal histopathological characteristics of patients with idiopathic membranous nephropathy (IMN) with different levels of proteinuria. Methods: This retrospective observational study included 190 IMN patients with low levels of proteinuria (low group), 193 IMN patients with medium levels of proteinuria (medium group), and 123 IMN patients with high levels of proteinuria (high group) treated between September 2006 and November 2015. Prognostic and baseline clinical and histopathological data were compared among the three groups. Poor prognostic events included the occurrence of a persistent 50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or all-cause mortality. Results: The severity of clinical symptoms and laboratory indices, such as blood pressure; extent of edema and hematuria; levels of fibrinogen, immunoglobulin (Ig)-G, complement (C)-4, total protein, albumin (ALB), and serum creatinine (SCr); and eGFR increased with increasing proteinuria (all p

Background: Guidelines recommend combined therapy of glucocorticoid and cyclophosphamide (CYC) for patients with idiopathic membranous nephropathy (IMN), while it is associated with severe adverse effects. We conducted a retrospective study to evaluate the effectiveness and safety of glucocorticoid plus tacrolimus (TAC) for IMN. Methods: Two hundred and three kidney-biopsy-proven IMN patients were enrolled in this study. One group (n = 142) received glucocorticoid combined with intravenous CYC (750 mg/m2 body surface) and the other group (n = 61) received glucocorticoid combined with oral TAC (target blood concentration of 4–8 ng/mL). The primary outcomes were achievement of remission and incidence of adverse events. The secondary end points included 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% versus 54.9%, p

Background: Several studies have revealed a relationship between proteinuria and renal prognosis in idiopathic membranous nephropathy (IMN). The benefit of achieving subnephrotic proteinuria (

Background: THSD7A is a new target antigen of idiopathic membranous nephropathy (IMN). Moreover, malignancies are also found in patients with THSD7A-positive membranous nephropathy. We aimed to systematically evaluate the prevalence of THSD7A in IMN patients and malignancies in THSD7A-positive patients. Methods: We searched English and Chinese database to 31 December 2017 with the term ‘THSD7A’ or ‘thrombospondin type 1 domain-containing 7A’. Meta-analysis was used to explore the positive rate of THSD7A in the IMN patients. Subgroup analysis was performed according to the race, sample size, and detecting method of THSD7A. Results: Ten studies involving 4121 participants were eventually included. The prevalence of THSD7A was 3% (95% CI, 3%–4%) in all patients and 10% (95% CI, 6%–15%) in PLA2R-negative patients. 77 patients had positive circulating antibodies, and the prevalence of THSD7A was also low at 3% (95% CI, 2%–4%). Overall, 72 patients had positive THSD7A staining on renal biopsy, and the prevalence was 3% (95% CI 2%–4%). Subgroup analysis showed significant differences in the prevalence of THSD7A based on the study sample sizes, however, no significant differences were seen in different ethnic groups. Furthermore, among THSD7A-positive patients, 3/10 studies reported malignancies with the incidence varied from 6% to 25%. Conclusions: The prevalence of THSD7A is more common in the PLA2R-negative patients than the IMN patients. Screening for malignancies in THSD7A-positive MN patients is recommended.

Background: This investigation was managed to explore whether miR-193a in combination with two podocytes, namely, Wilms tumor type 1 (WT1) and podocalyxin (PODXL), were feasible in estimating onset and prognosis of idiopathic membranous nephropathy (IMN). Methods: We recruited a total of 189 healthy controls and 364 IMN patients, whose urine samples were prepared to measure the expression of miR-193a and PODXL. Meanwhile, renal tissues collected from above-mentioned IMN patients (n = 364) and renal cell carcinoma patients (n = 189) were arranged to determine the expression of WT1. Ultimately, receiver operating characteristic curves were constructed to appraise the performance of miR-193a, WT1, and PODXL in predicting renal survival of IMN patients. Results: The IMN patients were measured with up-regulated miR-193a expression and down-regulated WT1/PODXL expression, when compared with healthy controls (p < 0.05). Moreover, highly expressed miR-193a, lowly expressed WT1/PODXL, elevated amounts of proteinuria (>3.79 g/24 h)/serum creatinine (>174.63 μmol/L), and declined GFR (≤68.13 mL/min/1.73 m2) were implicated as prominent biomarkers for the poor renal survival of IMN patients (all p < 0.05). Notably, miR-193a combined with PODXL and WT1 generated optimal effects in differentiating IMN patients from healthy controls (AUC = 0.994) and also in anticipating the renal survival state of IMN patients (AUC = 0.824), when compared with strategies that merely employed ≤2 of the biomarkers. Conclusion: The combination of miR-193a, WT1, and PODXL might serve as a favorable strategy for expecting IMN prognosis. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend combined therapy of glucocorticoid and cyclophosphamide (CYC) for patients with idiopathic membranous nephropathy (IMN), while it is associated with severe adverse effects. We conducted a retrospective study to evaluate the effectiveness and safety of glucocorticoid plus tacrolimus (TAC) for IMN. Methods: Two hundred and three kidney-biopsy-proven IMN patients were enrolled in this study. One group (n = 142) received glucocorticoid combined with intravenous CYC (750 mg/m2 body surface) and the other group (n = 61) received glucocorticoid combined with oral TAC (target blood concentration of 4–8 ng/mL). The primary outcomes were achievement of remission and incidence of adverse events. The secondary end points included 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% versus 54.9%, p <.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. 24hUP and serum albumin improved in TAC group more than the CYC group (p <.05) over the observed period. Conclusion: Because of its short-term effectiveness and long-term safety profile, glucocorticoid plus TAC might be a better option for IMN. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the unique prognostic, clinical, and renal histopathological characteristics of patients with idiopathic membranous nephropathy (IMN) with different levels of proteinuria. Methods: This retrospective observational study included 190 IMN patients with low levels of proteinuria (low group), 193 IMN patients with medium levels of proteinuria (medium group), and 123 IMN patients with high levels of proteinuria (high group) treated between September 2006 and November 2015. Prognostic and baseline clinical and histopathological data were compared among the three groups. Poor prognostic events included the occurrence of a persistent 50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or all-cause mortality. Results: The severity of clinical symptoms and laboratory indices, such as blood pressure; extent of edema and hematuria; levels of fibrinogen, immunoglobulin (Ig)-G, complement (C)-4, total protein, albumin (ALB), and serum creatinine (SCr); and eGFR increased with increasing proteinuria (all p<.001). Based on renal histopathology, the extent of segmental sclerosis and balloon adhesion and renal interstitial lesion stage also increased in severity with increasing proteinuria (all p<.001). The Kaplan–Meier analysis showed that compared with patients with low and medium levels of proteinuria, patients with high levels of proteinuria had significantly lower cumulative poor event-free renal survival rates (p=.0039). Conclusions: Baseline proteinuria level is indicative of prognosis in IMN patients; the greater the extent of proteinuria is, the worse the prognosis. [ABSTRACT FROM AUTHOR]

Background: Several studies have revealed a relationship between proteinuria and renal prognosis in idiopathic membranous nephropathy (IMN). The benefit of achieving subnephrotic proteinuria (<3.5 g/day), however, has not been well described. Methods: This multicenter, retrospective cohort study included 171 patients with IMN from 10 nephrology centers in Japan. The relationship between urinary protein over time and a decrease of 30% in estimated glomerular filtration rate (eGFR) was assessed using time-dependent multivariate Cox regression models adjusted for clinically relevant factors. Results: During the observation period (median, 37 months; interquartile range, 16-71 months), 37 (21.6%) patients developed a 30% decline in eGFR, and 2 (1.2%) progressed to end-stage renal disease. Time-dependent multivariate Cox regression models revealed that lower proteinuria over time were significantly associated with a lower risk for a decrease of 30% in eGFR (primary outcome), adjusted for clinically relevant factors. Complete remission (adjusted hazard ratio [HR], 0.005 [95%CI, 0.0-0.09], p < .001), incomplete remission with <1.0 g/day of urine protein (ICR I) (adjusted HR, 0.01 [95%CI, 0.001-0.20], p = .002), and 1.0 to 3.5 g/day (ICR II) (adjusted HR, 0.12 [95%CI, 0.02-0.64], p = .013) were significantly associated with avoiding a 30% decrease in eGFR, compared to that at no remission. Conclusions: Attaining lower proteinuria predicts good renal survival in Japanese patients with IMN. This study quantifies the impact of proteinuria reduction in IMN and the clinical relevance of achieving subnephrotic proteinuria in IMN as a valuable prognostic indicator for both the clinician and patient. [ABSTRACT FROM AUTHOR]

Background: THSD7A is a new target antigen of idiopathic membranous nephropathy (IMN). Moreover, malignancies are also found in patients with THSD7A-positive membranous nephropathy. We aimed to systematically evaluate the prevalence of THSD7A in IMN patients and malignancies in THSD7A-positive patients. Methods: We searched English and Chinese database to 31 December 2017 with the term 'THSD7A' or 'thrombospondin type 1 domain-containing 7A'. Meta-analysis was used to explore the positive rate of THSD7A in the IMN patients. Subgroup analysis was performed according to the race, sample size, and detecting method of THSD7A. Results: Ten studies involving 4121 participants were eventually included. The prevalence of THSD7A was 3% (95% CI, 3%-4%) in all patients and 10% (95% CI, 6%-15%) in PLA2R-negative patients. 77 patients had positive circulating antibodies, and the prevalence of THSD7A was also low at 3% (95% CI, 2%-4%). Overall, 72 patients had positive THSD7A staining on renal biopsy, and the prevalence was 3% (95% CI 2%-4%). Subgroup analysis showed significant differences in the prevalence of THSD7A based on the study sample sizes, however, no significant differences were seen in different ethnic groups. Furthermore, among THSD7A-positive patients, 3/10 studies reported malignancies with the incidence varied from 6% to 25%. Conclusions: The prevalence of THSD7A is more common in the PLA2R-negative patients than the IMN patients. Screening for malignancies in THSD7A-positive MN patients is recommended. [ABSTRACT FROM AUTHOR]

Introduction:The purpose of the study is to evaluate the efficiency and safety of tacrolimus (TAC) monotherapy in the treatment of nephrotic idiopathic membranous nephropathy (IMN) compared with the protocol of cyclophosphamide (CTX) combined with corticosteroids. Methods:In total, 58 patients with nephrotic syndrome and biopsy-proven IMN were included in this study. 30 patients received TAC monotherapy with an initial dose of 0.05–0.1 mg/kg/day. 28 patients received transvenous CTX at a dose of 0.5–0.75 g/m2once in every month initially for 6 months and once in every 2 or 3 months for the later period, and the regimen was combined with corticosteroids (prednisone 1 mg/kg/d). All patients were observed for the treatment effects, recurrence and side effects. Results:Twelve months after the initial treatment, a total of 24 (80%) patients in the TAC group and 23 (82.1%) patients in the CTX group achieved remission (either partial or complete remission). The survival curve of the probability of remission and complete remission were similar between the two groups (p > .05). Proteinuria (based on 24 h urinary protein excretion) was significantly decreased, and serum albumin was significantly increased after immunosuppressive treatment in both the groups. Estimated glomerular filtration rate (eGFR) was comparable between before and after treatment. The main adverse effects in TAC treatment were glucose intolerance, diabetes and abnormal aminotransferase. Conclusions:TAC monotherapy is an alternative therapeutic regimen for patients with nephrotic IMN. Its short-term efficiency and patient tolerance are both acceptable. [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.

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), β2-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.

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. Trial registration: retrospectively registered.

The studies of idiopathic membranous nephropathy (IMN) require sufficiently long duration of follow-up to understand the effect of treatment on the development of end-stage renal disease (ESRD) in IMN. The aim was to assess the remission rates with steroids and cyclophosphamide regimen for IMN at the end of 10 years of follow-up. A prospective, open-label study performed in Nephrology department of a state run tertiary care centre in a southern state of India. Adult (age >18 years) patients with biopsy-proven IMN of at least 6-month duration were included in the study. Patients received a 6-month course of alternate months of steroid and cyclophosphamide. The patients were followed for 10 years. Study end points were doubling of serum creatinine, development of ESRD, or death. A total of 58 IMN patients were recruited from 1997 to 2001. Out of 58 patients included, only 48 patients could complete the treatment schedule in six months. The remission rate at the end of 10 years was 58.6% (34 in 58 patients). The probability of dialysis-free survival in our study was 89.6% at the end of 10 years follow-up. The regimen of steroids and cyclophosphamide in IMN had a remission rates not as high as reported before. It was associated with high relapse rates and more infections. [ABSTRACT FROM AUTHOR]

In this prospective randomized trial, we compared the effects of cyclosporine- and cyclophosphamide-based treatment regimens in patients with idiopathic membranous nephropathy. Twenty-eight patients were randomized to receive treatment with one of the three therapeutic regimens: cyclosporine with methylprednisolone, cyclophosphamide with methylprednisolone or lisinopril (control). Renal function and nephrotic syndrome parameters were determined at baseline and during a 9-month treatment period. At the end of the study period, renal function improved significantly in the cyclophosphamide and deteriorated significantly in the cyclosporine group. Serum albumin levels increased significantly in the cyclosporine and cyclophosphamide group. Total cholesterol levels and proteinuria were significantly reduced in all groups. In the comparison between the groups, serum albumin levels were significantly lower in the control group and there were no differences in the rest of the studied parameters at the end of the study. Six patients from the cyclosporine group (1/10 complete and 5/10 partial), all cyclophosphamide-treated (4/8 complete and 4/8 partial) and all 10 lisinopril-treated patients (10/10 partial) were on remission at the end of the study. In conclusion, cyclosporine-based regimens are not inferior to cyclophosphamide-based regimens. Cyclophosphamide is associated with more complete remissions after 9 months of treatment. Lisinopril is associated with a significant proteinuria reduction and without inducing any complete remissions. [ABSTRACT FROM AUTHOR]