Aim To study the clinical profile and course and to assess the outcome of patients with biopsy-proven primary membranous nephropathy (MN). Methods This study was carried out in a tertiary care hospital between December 2017 and December 2021 on four-year retrospective biopsy-proven patients with membranous nephropathy (MN). Urinary proteins, serum albumin, and serum creatinine were the baseline investigations that were performed. Special tests were done whenever necessary. Patients were treated with a modified Ponticelli (MP) regimen whenever needed. Patients were followed up after treatment administration for a minimum of a year. Results The study was done in 48 biopsy-proven MN patients. Thirty-six patients had primary MN with a mean age of 47+/-11.7 years. The male-female ratio was 2.6:1. Hypertension was present in 39% (14 patients), microscopic hematuria in 28% (10 patients), and acute kidney injury in 22% (8 patients). The mean 24-hour urinary protein was 11.2+/-2.9 g/day. PLA2R was positive in 78% (28 patients) of primary MN patients. Spontaneous remission was noted in 13.8% (5 patients) who were treated conservatively. Spontaneous remission was associated with lower baseline proteinuria (p<0.001), higher baseline serum albumin (p<0.001), and PLA2R negativity (p=0.04). Complete or partial treatment response was noted in 74.2% (23 patients). Treatment remission was associated with lower baseline proteinuria (p=0.018). Secondary membranous nephropathy (secondary MN) was diagnosed in 12 patients. Eleven were class V lupus nephritis, all women, and one male person living with HIV/AIDS (PLHA). Conclusions The majority of our primary MN patients were PLA2R positive on renal biopsy. Statistically significant factors associated with spontaneous remission were lower proteinuria, higher serum albumin at baseline, and PLA2R negativity. Treatment response was associated with lower proteinuria at presentation. The most common cause of secondary MN was lupus nephritis.

Membranous nephropathy (MN) is a significant cause of nephrotic syndrome in non-diabetic adults. It can be primary, attributed to autoantibodies targeting podocyte antigens, or secondary to various disorders. Although rare, nerve epidermal growth factor-like 1 (NELL-1)-associated MN presents diagnostic and management challenges. Thrombotic complications such as renal vein thrombosis (RVT) are recognized but less reported, especially in NELL-1-positive MN. We report a 43-year-old male with NELL-1-positive MN complicated by acute kidney injury (AKI) due to bilateral RVT, treated successfully with thrombolysis. Histopathological analysis confirmed MN with specific immunohistochemical staining for NELL-1. Treatment included immunosuppressive therapy and tailored anticoagulation. This case emphasizes recognizing thrombotic complications in MN, particularly in NELL-1-positive cases. Further research is needed to explore serum anti-NELL-1 antibodies as biomarkers and optimal anticoagulation strategies in MN patients at risk of thrombotic events to improve outcomes and guide personalized management.

Previous studies showed tacrolimus monotherapy and dual therapy with tacrolimus and prednisone as effective treatment modalities in managing membranous nephropathy. However, few studies have compared these therapeutic regimens. The patients were divided into two groups based on the treatment regimen: (1) tacrolimus and prednisone dual therapy (T + P group, n = 67) treatment group; and (2) tacrolimus monotherapy (T group, n = 65) or the control group. Propensity matching method and subgroup analysis to eliminate the bias in the relationship between the treatment regimen and the outcomes. The mean remission times were 20.33 ± 2.75 weeks at T group and 9.50 ± 1.81 weeks at T + P group. The T group had a remission rates of 73.33, 76.66 and 66.66% at 12weeks, 24weeks and 48weeks, while the T + P group had a remission rate of 81.66, 86.66, 91.66%; At the follow-up of 48 weeks, the relapse rate for the T group was 21.66%, and that for the T + P group was 5%. The anti-PLA2R ab is positive and therapy may be the independent risk factors for predicting remission. Tacrolimus and low-dose prednisone dual therapy is efficacious in managing MN and lowers the recurrence rate in clinical practice.

The complement system, an important part of the innate system, is known to play a central role in many immune mediated kidney diseases. All parts of the complement system including the classical, alternative, and mannose-binding lectin pathways have been implicated in complement-mediated kidney injury. Although complement components are thought to be mainly synthesized in the liver and activated in the circulation, emerging data suggest that complement is synthesized and activated inside the kidney leading to direct injury. Urinary complement biomarkers are likely a better reflection of inflammation within the kidneys as compared to traditional serum complement biomarkers which may be influenced by systemic inflammation. In addition, urinary complement biomarkers have the advantage of being non-invasive and easily accessible. With the rise of therapies targeting the complement pathways, there is a critical need to better understand the role of complement in kidney diseases and to develop reliable and non-invasive biomarkers to assess disease activity, predict treatment response and guide therapeutic interventions. In this review, we summarized the current knowledge on urinary complement biomarkers of kidney diseases due to immune complex deposition (lupus nephritis, primary membranous nephropathy, IgA nephropathy) and due to activation of the alternative pathway (C3 glomerulopathy, thrombotic microangiography, ANCA-associated vasculitis). We also address the limitations of current research and propose future directions for the discovery of urinary complement biomarkers.

OBJECTIVE: This prospective single-arm trial with historic controls evaluated the efficacy and safety of treatment based on a combination of rituximab, intravenous cyclophosphamide, and corticosteroids (RCP) administered at lower cumulative doses for the induction of early remission in primary membranous nephropathy (PMN).
METHODS: We prospectively enrolled 30 high-risk PMN patients with persistent nephrotic syndrome (NS) and elevated antibodies to the phospholipase A2 receptor who underwent RCP therapy. We compared the effectiveness of RCP with that of historic controls who received rituximab-based therapy (RTX, n = 15) or cyclosporine + corticosteroids (CSA, n = 42). The primary outcomes were complete remission (CR) and overall remission (OR) by month 12 and the time to remission.
RESULTS: In the RCP group, the OR and CR rates by 12 months (97% and 60%) were higher than those in the RTX group (60% and 7%, P ≤ 0.009) and the CSA group (50% and 24%, P ≤ 0.003). The median time to OR (2.8 (1.6-3.9) months) was shorter compared to RTX (7.1 (3.4-17.5) months, P = 0.008) and CSA (7.3 (6.0-13.6) months, P < 0.001). In adjusted Cox regression, hazard ratios for OR and CR attainment for RCP versus other treatments were 5.2 (95% CI: 2.8-9.6) and 4.8 (95% CI: 2.2-10.3), respectively. Propensity score-matched group analyses confirmed these results. One serious adverse event occurred in the RCP group in the follow-up of 56 patient-years.
CONCLUSIONS: RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.

UNASSIGNED: The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC).
UNASSIGNED: This was tested in a prospective monocentric observational trial of 70 patients with PMN, of whom 34 received TAC (0.05-0.075 mg/kg/day) or 36 received TAC (0.05-0.075 mg/kg/day) and GC (0.3-0.5 mg/kg/day of prednisone).
UNASSIGNED: At 3, 6, 9, and 12 months of treatment, the effective rates in the TAC group and the TAC + GC group were similar (P > 0.05). The urinary protein quantification was reduced in patients under both therapeutic protocols, and the differences in the proteinuria quantification at 3, 6, 9, and 12 months of treatment were not statistically significant between the two groups (P > 0.05). The overall incidence of adverse reactions in the TAC group was lower than that in the TAC + GC group (23.5% < 36.1%), and the difference was statistically significant (P < 0.05).
UNASSIGNED: TAC monotherapy for PMN could effectively reduce urinary protein quantification and increase serum albumin levels. Compared with TAC + GC, TAC monotherapy for PMN had no difference in efficacy and fewer incidences of adverse reactions.

UNASSIGNED: The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN.
UNASSIGNED: 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman\'s correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission.
UNASSIGNED: In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766.
UNASSIGNED: FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.

BACKGROUND: As an initial treatment for primary membranous nephropathy (PMN), there remains a significant proportion of patients for whom rituximab is not fully effective. Here, we aimed to assess the effectiveness and safety of obinutuzumab as initial treatment in patients with PMN.
METHODS: In this observational case series, patients diagnosed with PMN and treated with obinutuzumab as initial treatment were included. Treatment response was assessed by 24-h urine total protein (24 h UTP) and serum albumin, and immunologic remission was assessed by phospholipase A2 receptor (PLA2R) antibodies.
RESULTS: Twelve patients with PMN receiving obinutuzumab as initial treatment were included. Over 6 months, a statistically significant reduction in 24 h UTP levels (p = 0.003) and an increase in serum albumin levels were observed (p < 0.001). By the 6-month follow-up, two patients (16.7%) achieved complete remission, eight (66.6%) reached partial remission, and two (16.7%) showed no remission. Immunological remission was observed in 44.4% of evaluable patients (n = 9) after 3 months, increasing to 100% (6/6) at 6 months. Except for cases 1, 2, and 3, the total B cell counts in the remaining patients fell to less than 5 cells/μL before the administration of the second dose of obinutuzumab, including seven patients with counts as low as 0 cells/μL. Mild to moderate treatment-related adverse events (TRAEs) were reported in 58.3% (7/12) of the patients. No serious TRAEs were reported.
CONCLUSIONS: Obinutuzumab demonstrates promising potential as an initial treatment for PMN, with good effectiveness and a manageable safety profile. Further large-scale prospective studies are needed to confirm these findings.

BACKGROUND: Primary membranous nephropathy (PMN) patients may experience retinal microvascular changes. However, current diagnostic methods for PMN are not accurate in analyzing these modifications. In the present study, optical coherence tomography angiography (OCTA) was used for quantitative measurement of microvascular changes in the eyes of PMN patients.
METHODS: A total of 26 patients with PMN and 26 healthy control (HC) were evaluated in this cross-sectional study. Optical coherence tomography (OCT) and OCTA were used to collect retinal thickness (RT) and microvascular parameters in the macula and optic disk in the superficial capillary plexus (SCP) of all subjects. Clinical data were collected from the PMN group. The OCT and OCTA data for PMN and HC group were compared, and the correlation between the OCTA and clinical data in the PMN group was determined.
RESULTS: Vascular density (VD) and perfusion density (PD) in the macular area of the PMN group were significantly lower than those of the HC group, especially in the temporal quadrant. No significant difference in the foveal avascular zone (FAZ), optic disc microvascular parameters, RT, and retinal nerve fiber layer (RNFL) thickness was observed between the two groups. Correlation was noted between VD and PD in the macular area and clinical indicators, such as serum creatinine, serum urea nitrogen, 24 h urine volume and urinary protein concentration.
CONCLUSIONS: Microvascular alterations in PMN patients occurred before ocular symptoms. The present quantitative study proposed a measurement method for detecting early retinal vascular injury in PMN patients.

Objective: This study aimed to build and validate a practical web-based dynamic prediction model for predicting renal progression in patients with primary membranous nephropathy (PMN). Method: A total of 359 PMN patients from The First Affiliated Hospital of Fujian Medical University and 102 patients with PMN from The Second Hospital of Longyan between January 2018 to December 2023 were included in the derivation and validation cohorts, respectively. Renal progression was delineated as a decrease in eGFR of 30% or more from the baseline measurement at biopsy or the onset of End-Stage Renal Disease (ESRD). Multivariable Cox regression analysis was employed to identify independent prognostic factors. A web-based dynamic prediction model for renal progression was built and validated, and the performance was assessed using. An analysis of the receiver operating characteristic and the decision curve analysis. Results: In the derivation cohort, 66 (18.3%) patients experienced renal progression during the follow-up period (37.60 ± 7.95 months). The final prediction rule for renal progression included hyperuricemia (HR=2.20, 95%CI 1.26 to 3.86), proteinuria (HR=2.16, 95%CI 1.47 to 3.18), significantly lower serum albumin (HR=2.34, 95%CI 1.51 to 3.68) and eGFR (HR=1.96, 95%CI 1.47 to 2.61), older age (HR=1.85, 95%CI 1.28 to 2.61), and higher sPLA2R-ab levels (HR=2.08, 95%CI 1.43 to 3.18). Scores for each variable were calculated using the regression coefficients in the Cox model. The developed web-based dynamic prediction model, available online at http://imnpredictmodel1.shinyapps.io/dynnomapp, showed good discrimination (C-statistic = 0.72) and calibration (Brier score, P = 0.155) in the validation cohort. Conclusion: We developed a web-based dynamic prediction model that can predict renal progression in patients with PMN. It may serve as a helpful tool for clinicians to identify high-risk PMN patients and tailor appropriate treatment and surveillance strategies.