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.

Primary membranous nephropathy (PMN) is the most common cause for adult nephrotic syndrome. Rituximab has demonstrated promising clinical efficacy by random controlled trials and the off-label use is widely adopted in PMN. However, the standard dosage is borrowed from B cell lymphoma treatment with far more antigens and is oversaturated for PMN treatment, accompanied with additional safety risk and unnecessary medical cost. More than 15% serious adverse events were observed under standard dosage and low dose therapies were explored recently. Dose optimization by clinical trials is extremely time- and cost-consuming and can be significantly accelerated with the aid of model-informed drug development. Here, we aim to establish the first population pharmacokinetic and pharmacodynamic (PPK/PD) model for rituximab in PMN to guide its dosage optimization. Rituximab pharmacokinetic and pharmacodynamic data from 41 PMN patients in a retrospective study under a newly proposed monthly mini-dose were used to construct quantitative dose-exposure-response relationship via mechanistic target-mediated drug disposition (TMDD) model followed by regression between the reduction of anti-PLA2R titer and time after the treatment. The final model, validated by goodness-of-fit plots, visual predictive checks and bootstrap, was used to recommend the optimized dosing regimen by simulations. The model was well validated for PK/PD prediction. The systemic clearance and half-life are 0.54 L/h and 14.7 days, respectively. Simulation of a novel regimen (6 monthly doses of 100 mg) indicated the comparable ability and superior duration time of CD20+ B cell depletion compared with standard dosage, while the cumulative dosage and safety risk was significantly decreased. We established the first PPK/PD model and provide evidence to support the dosage optimization based on monthly mini-dose. Our study can also efficiently accelerate dosage optimization of novel anti-CD20 antibodies in PMN and other indications.

There is evidence to suggest that M-type phospholipase A2 (PLA2R) antibodies activate the mannose-binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy-confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow-mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p < .01). MBL levels decreased significantly after immunosuppressive therapy (p = .04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [ρ] = 0.51: p = .01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients.

UNASSIGNED: This study aims to undertake a comprehensive assessment of the effectiveness and safety profile of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in the management of primary membranous nephropathy (PMN), within the context of a prospective clinical investigation.
UNASSIGNED: A multicenter, open-label clinical trial was executed on patients diagnosed with PMN. These individuals were subjected to MFSD therapy for a duration of at least 24 months, with primary outcome of clinical remission rates. The Cox regression analysis was employed to discern the pertinent risk factors exerting influence on the efficacy of MFSD treatment, with scrupulous monitoring of any adverse events.
UNASSIGNED: The study comprised 198 participants in total. Following 24 months of treatment, the remission rate was 58.6% (116/198). Among the subgroup of 130 participants subjected to a 36-month follow-up, the remission rate reached 70% (91/130). Subgroup analysis revealed that neither a history of immunosuppressive therapy (HIST) nor an age threshold of ≥60 years exhibited a statistically significant impact on the remission rate at the 24-month mark (p > .05). Multivariate Cox regression analyses elucidated HIST, nephrotic syndrome, or mass proteinuria, and a high-risk classification as noteworthy risk factors in the context of MFSD treatment. Remarkably, no fatalities resulting from side effects were documented throughout the study\'s duration.
UNASSIGNED: This trial establishes the efficacy of MFSD as a treatment modality for membranous nephropathy. MFSD demonstrates a favorable side effect profile, and remission rates are consistent across patients, irrespective of HIST and age categories.

BACKGROUND: International practice guidelines advocate for the use of anti-phospholipase A2 receptor (PLA2R) antibody testing to diagnose primary membranous nephropathy (pMN). This study aimed to clarify the current status of anti-PLA2R antibody testing in the diagnosis of pMN in Japan and to scrutinize the factors associated with the implementation of this antibody test.
METHODS: Utilizing a web-based questionnaire for nephrologists, responses were collected from 306 facilities and 427 nephrologists between November 2021 and December 2021. Preference for anti-PLA2R antibody testing was also investigated. Factors related to the experience of quantifying anti-PLA2R antibodies were estimated by generalized estimating equations using a robust analysis of variance with clusters of facilities of affiliation.
RESULTS: Of the 427 respondents, 140 (32.8%) had previous measurement experience at their current workplace and 165 (38.6%) had previous measurement experience overall. In pMN-suspected cases without contraindications to renal biopsy, 147 (34.4%) of the respondents opted to request anti-PLA2R antibody testing. The respondents\' experience with anti-PLA2R antibody quantification at their current place of work was generally higher in university hospitals and increased with the annual number of kidney biopsies and the number of years since graduation.
CONCLUSIONS: The results of this study suggest that a significant proportion of nephrologists in Japan have no experience in performing anti-PLA2R antibody assays, and that the assays may be hampered by the limited capabilities of the current workplace and the financial burden on facilities and patients.

BACKGROUND: Since primary membranous nephropathy is a heterogeneous disease with variable outcomes and multiple possible therapeutic approaches, all 13 Nephrology Units of the Italian region Emilia Romagna decided to analyze their experience in the management of this challenging glomerular disease.
METHODS: We retrospectively studied 205 consecutive adult patients affected by biopsy-proven primary membranous nephropathy, recruited from January 2010 through December 2017. The primary outcome was patient and renal survival. The secondary outcome was the rate of complete remission and partial remission of proteinuria. Relapse incidence, treatment patterns and adverse events were also assessed.
RESULTS: Median (IQR) follow-up was 36 (24-60) months. Overall patient and renal survival were 87.4% after 5 years. At the end of follow-up, 83 patients (40%) had complete remission and 72 patients (35%) had partial remission. Among responders, less than a quarter (23%) relapsed. Most patients (83%) underwent immunosuppressive therapy within 6 months of biopsy. A cyclic regimen of corticosteroid and cytotoxic agents was the most commonly used treatment schedule (63%), followed by rituximab (28%). Multivariable analysis showed that the cyclic regimen significantly correlates with complete remission (odds ratio 0.26; 95% CI 0.08-0.79) when compared to rituximab (p < 0.05).
CONCLUSIONS: In our large study, both short- and long-term outcomes were positive and consistent with those published in the literature. Our data suggest that the use of immunosuppressive therapy within the first 6 months after biopsy appears to be a winning strategy, and that the cyclic regimen also warrants a prominent role in primary membranous nephropathy treatment, since definitive proof of rituximab superiority is lacking.

Rituximab (RTX) is gaining increasing clinical acceptance in the treatment of primary membranous nephropathy (PMN), with demonstrated efficacy and safety. However, there are few clinical studies on RTX for PMN in Asian populations, especially in China.
To observe and analyse the efficacy and safety of RTX treatment, 81 patients with PMN suffering from nephrotic syndrome (NS) were enrolled and divided into an initial therapy group, a conventional immunosuppressive therapy relapse group, and a conventional immunosuppressive therapy ineffective group according to their pre-RTX treatment background. Patients in each group were followed up for 12 months. The primary outcome was clinical remission at 12 months, and the secondary outcomes were safety and the occurrence of adverse events.
At 12 months, 65 of 81 (80.2%) patients achieved complete (n=21, 25.9%) or partial (n=44, 54.3%) remission after rituximab treatment. Thirty-two of 36 (88.9%) patients in the initial therapy group, 11 of 12 (91.7%) patients in the relapse group and 22 of 33 (66.7%) patients in the ineffective group achieved clinical remission. All 59 patients with positive anti-PLA2R antibodies showed a decreasing trend in antibody levels after RTX treatment, and 55 (93.2%) of them achieved antibody clearance (<20 U/mL). Logistic regression analysis showed that a high anti-PLA2R antibody titer (OR=0.993, P=0.032) was an independent risk factor for nonremission. Adverse events occurred in 18 (22.2%) patients, of which 5 (6.2%) were serious adverse events, and none were malignant or otherwise fatal.
RTX alone can effectively induce remission PMN and maintain stable renal function. It is recommended as the first choice of treatment and is also effective in patients who relapse and have poor responses to conventional immunosuppressive therapy. Anti-PLA2R antibodies can be used as a marker for RTX treatment monitoring, and antibody clearance is necessary to achieve and improve the rates of clinical remission.

Primary membranous nephropathy (PMN) is the most frequent cause of nephrotic syndrome in adults. Rituximab monotherapy has emerged as a front-line treatment for patients with PMN, but potential markers for predicting the response to rituximab are unknown.
In this single-arm retrospective pilot study, 48 patients with PMN without previous immunosuppressive therapy were enrolled. All patients were treated with rituximab and were followed up for at least 6 months. The primary end point was the achievement of complete or partial remission at 6 months. The subsets of lymphocytes were collected at baseline, 1 month, 3 months and 6 months to identify prognostic factors for achieving remission of PMN with rituximab therapy.
A total of 58.3% of patients (28/48) achieved remission. Lower serum creatinine, greater serum albumin, and greater phospholipase A2 receptor antigen detected in kidney biopsy at baseline were found in the remission group. After multiple adjustments, a high percentage of natural killer (NK) cells at baseline, especially ≥15.7%, was strongly associated with remission (relative risk = 1.62; 95% CI, 1.00-2.62; P = 0.049), and patients with a response to rituximab had a greater mean percentage of NK cells during the follow-up period compared with nonresponders. Analysis using a receiver operating characteristic curve indicated prognostic value of the NK-cell percentage at baseline, with an area under the curve of 0.716 (95% CI, 0.556-0.876; P = 0.021).
The findings from this retrospective pilot study suggest that a high percentage, especially ≥15.7%, of NK cells at baseline might predict a response to rituximab treatment. These findings provide a basis for designing larger-scale studies to test the predictive value of NK cells in patients with PMN undergoing rituximab treatment.

BACKGROUND: We aimed to initially explore the efficiency and safety of mizoribine (MZR) combined with steroids and dietary sodium restriction on the treatment of primary membranous nephropathy (MN) compared with cyclophosphamide (CPM)-based steroids.
METHODS: Patients with primary MN were enrolled. According to the therapy, they were divided into the MZR combined with steroids and dietary sodium restriction group (N = 30) and CPM-based steroids group (N = 30). Both groups were followed up for 1 year to monitor safety and efficacy.
RESULTS: Compared with the CPM-based steroids group, the MZR combined with steroids and dietary sodium restriction group had significantly lower daily sodium intake, serum sodium, blood pressure (BP), and 24 h urine protein (all P < 0.05). Conversely, plasma albumin and complete remission rate in the MZR group were higher at the 12th follow-up (40.39 ± 5.14 g/L vs. 37.63 ± 5.40 g/L; 86.67% vs. 66.67%; all P < 0.05). These two groups showed similar adverse events rates (20.00% vs. 26.67%, P = 0.54).
CONCLUSIONS: This study demonstrates that MZR combined with steroids and dietary sodium restriction is superior to CPM-based steroids in terms of complete remission and 24 h urine protein in patients with primary MN.

BACKGROUND: Serious infections are an important concern for patients with autoimmune conditions. We sought to estimate serious infection rates among patients with select autoimmune conditions relative to the general population in Taiwan and the USA.
METHODS: This retrospective cohort study estimated setting-specific standardized serious infection incidence rates and ratios among patients with systemic lupus erythematosus, including extra-renal lupus and lupus nephritis, rheumatoid arthritis and primary membranous nephropathy, compared with the general population using insurance claims for hospitalizations between 2000 and 2013. Multivariable Cox proportional hazard models were used to estimate adjusted hazard ratios for serious infections, adjusting for age, sex, index year, prior serious infection, comorbidities and medications.
RESULTS: In Taiwan, serious infection rates were 22.7, 28.7, 70.6, 43.4 and 215.3 per 1000 person-years among the general population and among cohorts of patients with primary membranous nephropathy, rheumatoid arthritis, extra-renal lupus and lupus nephritis, respectively. In the USA, serious infection rates were 2.6, 9.0, 15.6, 21.0 and 63.3 per 1000 person-years among the general population and among cohorts of patients with primary membranous nephropathy, rheumatoid arthritis, extra-renal lupus and lupus nephritis, respectively. Patients had significantly higher serious infection rates than the general population in both settings, largely driven by bacterial, respiratory, urinary tract and opportunistic infections. Patients with lupus nephritis had the highest burden of serious infections relative to the general population, with 7- to 25-fold higher adjusted hazard ratios in Taiwan and the USA, respectively.
CONCLUSIONS: This study identified a significant excess serious infection burden among patients with targeted autoimmune conditions compared with the general populations in Taiwan and the USA.