Membranous Nephropathy Research Articles

A multicenter retrospective study on comparing the efficacy and safety of the therapy of intermittent cyclophosphamide and corticosteroids versus rituximab for primary membranous nephropathy.

Few clinical studies compare the long-term remission, relapse, and safety of rituximab (RTX) or a combination of intermittent intravenous infusion of cyclophosphamide (CTX) and oral corticosteroid for primary membranous nephropathy (PMN) patients. We collected multicenter retrospective data on PMN patients with nephrotic syndrome who received RTX or intermittent intravenous CTX with oral corticosteroids between 1 January 2019 and 31 January 2024. Patients were followed up until two years after receiving immunotherapy. The primary outcomes were a composite of complete or partial remission rates at 6, 12, and 24months. The secondary outcomes were the relapse and safety evaluation. Forty patients treated with RTX and 27 with the CTX regime were available for analysis. No significant difference in the remission rate at 6, 12, or 24months was observed between the two groups (p>.05). Kaplan-Meier's survival analysis showed that the relapse-free cumulative survival rate of the RTX group was superior to that of the CTX group (p=.023). Compared with baseline, both the media of urine protein and serum albumin levels in the two groups showed a significant improvement at 6months and maintained through to the second year. No significant difference in the occurrence of total side effects between the two groups (p=.160). There was no difference in remission rates and safety between RTX versus intermittent intravenous CTX combined with oral corticosteroid treatment for patients with PMN within 2years. RTX appeared to have benefits in terms of prolonging relapse-free survival.

Genetic susceptibility to idiopathic membranous nephropathy in high-prevalence Area, Taiwan

Genetic susceptibility to idiopathic membranous nephropathy in high-prevalence Area, Taiwan

Primary glomerular diseases and long-term adverse health outcomes: A nationwide cohort study.

Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes. In patients with chronic kidney disease (CKD) stage 3-5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD). We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29mL/min/1.73m2, uACR 88mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25mL/min/1.73m2, uACR 23mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45-0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15-1.37] and 1.34 [1.15-1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline. Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients.

The association between serum complement 4 and relapse of primary membranous nephropathy: a multicenter retrospective cohort study

BackgroundRelapse after initial remission reduces renal survival in patients with primary membranous nephropathy (PMN). In this study, we aim to identify risk factors of relapse in PMN and construct a model to identify patients at high risk of relapse early.MethodsWe conducted a multi-center retrospective study using the China Renal Data System database, which includes data from 24 urban academic centers across China. A prediction model based on the Cox proportional hazards model was derived in the derivation group and validated in the validation group.Result515 patients with biopsy-proven PMN achieving initial remission were enrolled. 32.62% of patients subsequently relapsed during a median of 6.08 months. Lower serum albumin (Alb) (per 1 g/L decrease, hazard ratio [HR] =1.48, 95% confidence interval [CI] 1.29–1.78, p < 0.001), lower estimated glomerular filtration rate (eGFR) (per 10 mL/min/1.73m2 decrease, HR =1.14, 95% CI 0.97–1.49, p < 0.001), higher serum complement 4 (C4) (per 0.1 g/L increase, HR =1.89, 95% CI 1.32–3.22, p = 0.012), partial remission (PR) (HR =2.28, 95%CI 1.74–4.04, p < 0.001), and treatment with calcineurin inhibitors (CINs) (HR =1.33, 95%CI 1.04–1.64, p < 0.001) at the time of remission were risk factors for relapse. C-statistic, time-dependent areas under the receiver operating characteristic curve, and calibration plots confirmed that the model had excellent discrimination and calibration in predicting PMN relapse. The anti-phospholipase A2 receptor antibody (aPLA2Rab) titers and pathologic features did not substantially improve the model.ConclusionOur study confirms the well-known low Alb and eGFR, PR, and treatment of CNIs at the time of remission as risk factors for PMN relapse, but aPLA2Rab and pathologic features may not predict relapse. In addition, it is the first study to show serum C4 is associated with PMN relapse. We suggest that complement-targeted therapies may be a potential therapy to prevent PMN relapse.

A case of PLA2R-positive membranous nephropathy with subsequent development of IgG4-related disease.

Membranous nephropathy (MN) is a common cause of adult-onset nephrotic syndrome. It is also known as a minor but established renal manifestation of Immunoglobulin G4-related disease (IgG4-RD). Previous reports suggest that MN can also be an initial manifestation of IgG4-RD, all of which are phospholipase A2 receptor (PLA2R)-negative MN. We describe a case of PLA2R-positive MN that subsequently developed other manifestations of IgG4-RD. A 60-year-old male with nephrotic syndrome was diagnosed as primary MN with positive staining for PLA2R on the initial renal biopsy, which remained in partial remission with supportive therapy using angiotensin II receptor blocker (ARB) without steroid. About 1year later, a renal mass was detected during an annual checkup, and contrast-enhanced computed tomography revealed low-density masses in bilateral kidneys and the head of the pancreas. The findings of endoscopic biopsy of the pancreatic mass were consistent with autoimmune pancreatitis (AIP) and the second renal biopsy showed the findings of MN with tubulointerstitial nephritis, both of which led to a diagnosis of IgG4-RD. The second renal biopsy also showed positive PLA2R. The patient received oral glucocorticoid therapy for IgG4-RD, which improved IgG4-related AIP and renal masses and also resulted in complete remission of MN. To our knowledge, this is the first reported case of PLA2R-positive MN with subsequent development of IgG4-RD. It is sometimes difficult to determine whether PLA2R-positive MN occurring with IgG4-RD is primary MN or secondary MN associated with IgG4-RD. The possibility of developing IgG4-RD should be considered even when preceding MN is PLA2R-positive, suggesting of primary MN.

The Relationship Between Mercury Exposure and Membranous Nephropathy: Case Reports and Meta-Analysis.

To investigate the clinical characteristics of patients with membranous nephropathy (MN) and the therapeutic efficacy of Sodium Dimercaptosulphonate (DMPS), as well as the relationship between mercury (Hg) exposure and MN, we investigated the clinical manifestations and treatment outcomes of six patients with MN and searched the China National Knowledge Internet (CNKI), PubMed, Web Of Science, and Embase databases for relevant studies on Hg exposure and MN published from the inception of the databases to April 2024. Data analysis was performed using SPSS 26.0 and Stata 16.0. We found that (1) the clinical symptoms of MN patients were mainly characterized by proteinuria, edema, hypoproteinemia, and hyperlipidemia. Comparative analysis before and after DMPS treatment showed a decrease in 24-h urinary Hg, 24-h urinary protein, and total cholesterol levels, as well as an increase in serum albumin levels (p < 0.05). (2) Two MN patients received DMPS for sole Hg detoxification treatment, whereas four patients received Hg detoxification combined with hormone therapy, and all patients showed significant improvement in symptoms after treatment. (3) Among the 564 articles, four met the inclusion criteria. The results showed that Hg exposure increased the incidence of MN by 5.74 times (95% confidence interval [CI] = 2.57, 12.83). The clinical symptoms of MN patients are mostly manifested as proteinuria, edema, hypoproteinemia, and hyperlipidemia. DMPS Hg detoxification treatment is effective for Hg-induced MN. Hg exposure can increase the prevalence of MN, therefore making it necessary to take prudent measures to reduce the risk of Hg exposure.

Prognostic value of serum complement cleavage factor Bb in idiopathic membranous nephropathy and establishment of nomogram model

Complement activation is involved in idiopathic membranous nephropathy (IMN). We aimed to investigate the relationship of serum complement cleavage factor Bb with IMN progression, and to establish a model for early prediction of kidney outcomes. We measured serum factor Bb in a retrospective cohort of 449 IMN patients at the time of kidney biopsy. Cox regression analysis showed that higher levels of serum factor Bb were independently associated with IMN progression event defined as end-stage renal disease or ≥ 40% decline in estimated glomerular filtration rate. Patients in the middle and highest tertiles of serum factor Bb had respectively 2.1-, and 2.6-fold higher risk for disease progression compared with those in the lowest tertile. We developed an optimized prognostic nomogram model incorporating age, log serum anti-PLA2R antibody, log serum Bb, proteinuria and tubular atrophy/interstitial fibrosis. The model demonstrated good predictive ability with a concordance index of 0.77 (bootstrap-corrected of 0.76) for predicting 3-, and 5-year kidney survival. Calibration curves and decision curve analysis confirmed the model’s good calibration and clinical utility. Our findings suggest that serum factor Bb may serve as an essential prognostic indicator of IMN. The novel nomogram model may offer important guidance on the management of this patient population.

Updated diagnostic and therapeutic management for membranous nephropathy.

Pioneering contributions in membranous nephropathy over the last decade have greatly enhanced our comprehension of its pathogenesis, diagnosis, and treatments, igniting renewed interest in this entity. This review provides an updated perspective on the diagnosis and therapeutic management of membranous nephropathy. The identification of antiphospholipase A2 receptor (PLA2R) antibodies in 50-80% of membranous nephropathy patients was a key breakthrough. High or increasing PLA2R antibody levels are linked to persistent nephrotic syndrome and the need for targeted treatment. Given the high specificity of PLA2R antibodies, a kidney biopsy may not be required for pure nephrotic syndrome cases with no comorbidities. Over the years, various target antigens and associated conditions have been identified in membranous nephropathy patients, leading to a reclassification of membranous nephropathy. Treatment approaches vary based on baseline characteristics and changes in proteinuria and PLA2R titers. Rituximab has emerged as the first-line therapy for most patients without severe risk factors, with other emerging therapies under development. Advances in the diagnosis and treatment of membranous nephropathy have moved the management towards a more precision-based approach, though further studies and new therapies are needed for a comprehensive management strategy.

Investigating potential drug targets for IgA nephropathy and membranous nephropathy through multi-queue plasma protein analysis: a Mendelian randomization study based on SMR and co-localization analysis

BackgroundMembranous nephropathy (MN) and IgA nephropathy (IgAN) pose challenges in clinical treatment with existing therapies primarily focusing on symptom relief and often yielding unsatisfactory outcomes. The search for novel drug targets remains crucial to address the shortcomings in managing both kidney diseases.MethodsUtilizing GWAS data for MN (ncase = 2150, ncontrol = 5829) and IgAN (ncase = 15587, ncontrol = 462197), instrumental variables for plasma proteins were derived from recent GWAS. Sensitivity analysis involved bidirectional Mendelian randomization analysis, MR Steiger, Bayesian co-localization, and Phenotype scanning. The SMR analysis using eQTL data from the eQTLGen Consortium was conducted to assess the availability of selected protein targets. The PPI network was constructed to reveal potential associations with existing drug treatment targets.ResultsThe study, subjected to the stringent Bonferroni correction, revealed significant associations: four proteins with MN and three proteins with IgAN. In plasma protein cis-pQTL data from two cohorts, an increase in one standard deviation in PLA2R1 (OR = 2.01, 95%CI = 1.83–2.21), AIF1 (OR = 9.04, 95%CI = 4.69–17.41), MLN (OR = 3.79, 95%CI = 2.12–6.78), and NFKB1 (OR = 29.43, 95%CI = 7.73–112.0) was associated with an increased risk of MN. Additionally, in plasma protein cis-pQTL data, a standard deviation increase in FCGR3B (OR = 1.15, 95%CI = 1.09–1.22) and BTN3A1 (OR = 4.05, 95%CI = 2.65–6.19) correlated with elevated IgAN risk, while AIF1 (OR = 0.58, 95%CI = 0.46–0.73) exhibited IgAN protection. Bayesian co-localization indicated that PLA2R1 (coloc.abf-PPH4 = 0.695), NFKB1 (coloc.abf-PPH4 = 0.949), FCGR3B (coloc.abf-PPH4 = 0.909), and BTN3A1 (coloc.abf-PPH4 = 0.685) share the same variants associated with MN and IgAN. The SMR analysis indicated a causal link between NFKB1 and BTN3A1 plasma protein eQTL in both conditions, and BTN3A1 was validated externally.ConclusionGenetically influenced plasma levels of PLA2R1 and NFKB1 impact MN risk, while FCGR3B and BTN3A1 levels are causally linked to IgAN risk, suggesting potential drug targets for further clinical exploration, notably BTN3A1 for IgAN.

Establishment of a high-sensitivity time-resolved fluorescence immunoassay with PLA2R-IgG1 antibody and its clinical application in idiopathic membranous nephropathy prognosis

IntroductionThe objective of this study was to develop a highly sensitive time-resolved fluorescence immunoassay (TRFIA) method to detect phospholipase A2 receptor (PLA2R)-IgG1 antibodies and evaluate its clinical relevance in predicting the prognosis of individuals with idiopathic membranous nephropathy (IMN). Materials and methodsA three-step indirect TRFIA method was established using a PLA2R antigen-coated microtiter plate to capture PLA2R-IgG antibodies, followed by detection using mouse anti-human IgG1 and Eu3+-labeled goat anti-mouse IgG antibodies. This method was applied to the initial serum of 56 patients with PLA2R-IMN to investigate the clinical value of PLA2R-IgG1 antibody levels in predicting IMN prognosis. ResultsThe detection range of PLA2R-IgG1-TRFIA was 0.85–300RU/mL, with intra-assay precision of 3.54–5.93 % and inter-assay precision of 4.39–9.36 %. Recoveries were 101.77–108.04 %. A PLA2R-IgG1 level above 2.21RU/mL indicated PLA2R-IMN. At initial diagnosis, the median PLA2R-IgG level was 51.24RU/mL in the remission group and 93.27RU/mL in the non-remission group. The median PLA2R-IgG1 level was 603.32RU/mL in the non-remission group, which was 4.29 times higher than that in the remission group (140.67RU/mL). PLA2R-IgG1 levels (P = 0.001) more effectively distinguished between remission and non-remission groups compared with PLA2R-IgG levels (P = 0.094). ConclusionsThe first quantitative TRFIA for PLA2R-IgG1 was established, showing greater clinical value in predicting IMN prognosis, compared to that for PLA2R-IgG levels.

Single-dose telitacicept therapy for refractory idiopathic membranous nephropathy: A case series.

We report three cases of IMN from our center, where patients received a single dose of telitacicept after showing no response to conventional treatments. Although one case did not respond, the other two cases achieved complete or partial remission of proteinuria. These cases illustrates the telitacicept may offer new hope for the treatment of IMN. Despite the variety of treatment options available, effective therapies for refractory membranous nephropathy remain lacking. Recently, some reports have suggested that telitacicept is a new therapeutic option. However, only a few published studies have documented the use of telitacicept for treating idiopathic membranous nephropathy (IMN). We present three cases of IMN from our center, where patients received a single dose of telitacicept after showing no response to conventional treatments, including glucocorticoids, tacrolimus, mycophenolate mofetil, cyclophosphamide, cyclosporine, and rituximab. Although one case did not respond, the other two cases achieved complete or partial remission of proteinuria. Thus, telitacicept may offer new hope for the treatment of refractory membranous nephropathy.

Evaluating the risk of cardiovascular events associated with different immunosuppression treatments for glomerular diseases.

Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association between exposure to specific immunosuppressive medications and a composite outcome including coronary artery, cerebrovascular and peripheral arterial events. Survival models were adjusted for baseline cardiovascular risk factors, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. During a median follow-up of 6.8 years, 212 patients (11.1%) experienced the primary outcome. Corticosteroid exposure was not significantly associated with the primary outcome after adjusting for cardiovascular risk factors. In fully adjusted models, cumulative calcineurin inhibitor exposure at modest (150-300 defined daily doses [DDD]) and higher (300 or more DDD) doses were associated with a 2-fold higher risk of cardiovascular events (hazard ratio 2.98, 95% confidence interval 1.27-6.95) and (2.78, 1.32-5.84), respectively. A peak daily dose of antimetabolite (azathioprine, mycophenolate mofetil and mycophenolate sodium) of 0.5 or more DDD was associated with higher risk of cardiovascular events after adjustment for baseline risk factors and type of glomerular disease, but not after adjusting for time-varying eGFR and proteinuria (1.70, 0.91-3.20). Each 10 grams of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events in a fully adjusted model (1.46, 1.22-1.75) Thus, our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials.

Locality Cross-domain Discriminant Analysis for Membranous Nephropathy Recognition Using Microscopic Hyperspectral Imaging.

Cross-domain methods have been proposed to learn the domain invariant knowledge that can be transferred from the source domain to the target domain. Existing cross-domain methods attempt to minimize the distribution discrepancy of the domains. However, these methods fail to explore the domain invariant subspace due to the samples of different classes between two domains may overlap in the new subspace. They consider the features in the original space data that may be unnecessary or irrelevant to the final classification, and neglect to preserve the local manifold structure between two domains. To solve these problems, a novel feature extraction method called Locality Cross-domain Discriminant Analysis (LCDA) is proposed. LCDA first aligns the distributions and avoids overlap between two domains. Then, LCDA exploits the local manifold structure to maintain the discriminative capability of the low-dimensional projection matrices. Finally, a robust constraint is utilized to preserve the robustness of the projection matrices. The proposed LCDA not only avoids overlap between different classes but also explores the local manifold information. Experiment results on the medical membranous nephropathy hyperspectral dataset demonstrate that the proposed LCDA has better performance than other relevant feature extraction methods.

What is the spectrum of kidney pathology associated with COVID-19?

Kidney involvement occurs in almost one third of patients hospitalised with coronavirus disease 2019 (COVID-19) and is associated with increased disease severity. This review aims to outline the spectrum of kidney pathology involved in COVID-19. Literature was reviewed systematically on the databases Medline OVID and Scopus in search of case reports, case series, cohort studies and autopsy studies of patients with COVID-19 who underwent kidney biopsies. Studies were published between August 2020 and November 2021. Fourteen studies consisting of 159 patients were included in this review. Acute tubular necrosis is the most common pathology followed by collapsing glomerulopathy, occurring in 40.1% and 28.9% of patients respectively. Of the 46 patients with collapsing glomerulopathy, 44 were of African descent with high-risk apolipoprotein L1 genotypes. Less common glomerular diseases include membranous nephropathy, secondary focal segmental glomerulosclerosis, minimal change disease and primary focal segmental glomerulosclerosis occurring in 5%, 4.4%, 3.1% and 2.5% of patients respectively. Glomerulonephritis occurred in a minority of patients. Direct viral infection has not been found as a definitive aetiology. Acute kidney injury occurs frequently in hospitalised COVID-19 patients and is associated with increased morbidity and mortality. The mechanisms underpinning acute kidney injury are multifactorial. Acute tubular necrosis is the most common. Collapsing glomerulopathy is the most common glomerular injury and is strongly linked to apolipoprotein L1 genotypes. Improved understanding of COVID-19-related kidney pathologies can guide treatment to improve patient outcomes and reduce progression of chronic kidney disease. The longitudinal impact of COVID-19-related kidney disease requires further research.

Efficacy and safety of Chinese herbal medicines combined with biomedicine in the treatment of idiopathic membranous nephropathy: a systematic review and network meta-analysis.

Chinese herbal medicines have been extensively used to treat idiopathic membranous nephropathy (IMN). However, their efficacy and safety remain uncertain. Therefore, this study employed a network meta-analysis to evaluate the efficacy and safety of various Chinese herbal medicines in combination with biomedicines for treating IMN. A comprehensive literature search was performed across several databases, including PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Data, VIP Database, and Chinese Biomedical Literature Database (CBM), to identify randomized controlled trials (RCTs) concerning the treatment of IMN using a combination of Chinese herbal medicines and biomedicine, up to 31 May 2024. Two researchers independently conducted the literature screening and data extraction. The quality of the included studies was assessed using the Cochrane quality review manual, and Stata 14.2 software was employed for network meta-analysis. A total of 31 RCTs involving 2195 IMN patients and 15 different Chinese herbal medicines were analyzed. The network meta-analysis revealed that QQC + BM (84.7%) was the most effective in reducing 24-hour urinary protein. For improving serum albumin, HZC + BM (86%) was the most effective. LGT + BM (77.2%) was the best for enhancing serum creatinine levels. MXC + BM demonstrated the highest effectiveness in lowering total cholesterol (89%) and triglycerides (97%). Lastly, WZC + BM (90.8%) was the most effective in reducing the incidence of adverse reactions. BM. The current evidence suggests that integrating Chinese herbal medicines with biomedicine may provide significant benefits in treating IMN. Specifically, QQC + BM appears to be the most effective in reducing 24-hour urinary protein, HZC + BM seems to excel in improving serum albumin levels, MXC + BM is noted for its effectiveness in lowering triglycerides and total cholesterol, LGT + BM is optimal for reducing serum creatinine, and WZC + BM shows the lowest rate of adverse reactions. Nevertheless, due to limitations in the quantity and quality of the included studies, further validation of these conclusions is necessary. [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024561028], identifier [CRD42024561028].

Clinicopathological Features of Membranous Nephropathy Complicated by IgA Nephropathy: A Retrospective Analysis of Seven Cases.

Aims/Background Both membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) are immune complex-mediated glomerular diseases, but the concurrent occurrence of these two conditions in the same patient is not common, a phenomenon that is currently not supported by clinical data in terms of treatment and prognosis. This study explores the clinical and pathological characteristics, as well as the treatment outcomes, of patients affected by MN and IgAN simultaneously. Methods The clinical data, pathological features, and diagnostic and therapeutic information of seven cases of MN complicated by IgAN, treated between December 2015 and December 2022, were retrospectively analyzed. Results Among the seven cases, there were two male and five female patients, with an average age of 57.3 ± 9.2 years. All patients presented with clinical manifestations of proteinuria and edema upon admission, with an average 24-hour urine protein of 3716.6 ± 1519.4 mg/24 h. Phospholipase A2 receptor (PLA2R) expression was detected in all seven cases, and nephrotic syndrome was clinically diagnosed in five cases. Additionally, all seven cases showed microscopic hematuria, with intermittent gross hematuria in two cases. All seven patients included in this study underwent renal biopsy. After disease staging, the patients had MN stages I-III and IgAN stages II-III. Pathological findings revealed abnormal glomerular basement membrane (GBM) and diffuse immunoglobulin G (IgG) deposition in the subepithelial space, predominantly of the IgG4 subtype. Simultaneously, there was diffuse mesangial zone deposition of immunoglobulin A (IgA) to varying degrees, co-localization of complement component C3 and IgA, and mesangial cell proliferation. Treatment strategies included angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in combination with steroids or immunosuppressive therapies such as tacrolimus, cyclophosphamide, and rituximab. After 2-6 months of treatment, all patients achieved complete remission with a favourable prognosis. Conclusion MN accompanied by IgAN tends to occur more frequently in middle-aged and elderly individuals, with a relatively low incidence. The latent feature of the comorbidities manifests as a form of IgAN superimposed on the background of MN. Utilizing ACEI or ARB in combination with steroids or various immunosuppressive therapies represents a potentially effective treatment strategy.

Kidney injury: An overlooked manifestation in autoimmune encephalitis

AimTo investigate the prevalence and clinical features of kidney injury in patients with autoimmune encephalitis (AE). MethodsKidney injury was suspected in kidney-involving group due to persistent abnormal in urinary protein and serum albumin. Data on demographics and clinical features were compared between kidney-involving group and kidney-sparing group (patients without kidney injury) using Wilcoxon rank-sum test or chi-square test. Renal biopsy was conducted to identify the type of kidney injury. ResultsApproximate 30 % (32 of 108) patients with AE were suspicious of kidney injury. Nine patients further tested 24 h urine total protein, and seven of them had an elevated urine protein higher than 150 mg. The predominantly patterns of kidney injury were elevated urine protein, decreased serum albumin and normal kidney function. Compared to kidney-sparing group, the spectrum of AE antibodies in kidney-involving group was different, manifested as less anti-N-methyl-d-aspartate receptor antibodies (50 % vs. 72.4 %, p = 0.025) and more anti-contactin-associated protein like 2 antibodies (18.8 % vs. 1.3 %, p = 0.003). Definite pathological changes indicative of IgA nephropathy and membranous nephropathy in renal biopsy of two cases provided evidence of autoimmune attacks. DiscussionKidney injury occurred in considerable proportion of patients with AE. An in-depth screening for nephropathy could be essential for AE.

Association between immune cells and membranous nephropathy: a two-sample Mendelian randomization study

IntroductionMultiple studies have indicated that immune cells play a significant role in the occurrence and development of membranous nephropathy (MN). However, the causal relationship between the two has not been fully established. To further investigate this, we employed a Mendelian randomization (MR) study design.Material and methodsGenetic instrumental variables for immune cells were sourced from an extensive genome-wide association study (GWAS). MN summary statistics, involving 2,150 cases and 5,829 controls, were obtained from a separate GWAS. The primary analysis employed the inverse-variance weighted (IVW) method. To explore reverse causation, a reverse MR analysis was undertaken. Rigorous sensitivity analyses were conducted to ensure the resilience and reliability of the study's findings.ResultsWe identified eight immunophenotypes associated with a reduced risk of MN and all of them were the protective factors for MN. The sensitivity analyses consistently yielded similar results for these immune traits. In the reverse MR analysis, we did not observe any statistically significant associations between MN and these eight immunophenotypes.ConclusionsOur study, utilizing genetic approaches, provides evidence for a causal relationship between immune cells and MN, which has implications for clinical diagnosis and treatment. Further comprehensive investigations are needed to explore the detailed mechanisms underlying the impact of immune cells on MN.

Overview of Immunological Response in Urological Membranous Nephropathy: Focus on Cytokine and Treatment Options.

Membranous nephropathy (MN) is an autoimmune disease that is caused by the production of autoantibody against glomerular podocyte antigens by immune cells due to the lack of self-tolerance mechanisms. Similar to many autoimmune diseases, the pathogenesis of MN is still vague and many experiments are being conducted to detect the antigens and genetic reasons for MN illness. Recently, new antigens, such as exotosin 1/exotosin 2, neural EGF-like-1, semaphorin 3B, and protocadherin 7 have been identified in MN patients who did not have presence of antiphospholipase A2 receptor antigen. What is more, cytokines, which are molecules that regulate immune responses, have been found to have harmful effects in various autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and MN. The role of cytokines and treatment strategies in MN patients is discussed in this article. As the understanding of the disease improves, targeted therapies that focus on specific antigens or cytokines may be developed to effectively manage MN.

Effects of immunosuppressive therapy on renal prognosis in primary membranous nephropathy

BackgroundImmunosuppressive therapy plays a crucial role in treating membranous nephropathy, with previous studies highlighting its benefits for patients with primary membranous nephropathy (PMN). Guidelines suggest that the management of membranous nephropathy should be tailored to individual risk levels. However, there is a lack of real-world studies examining the effects of immunosuppressive therapy on renal outcomes in PMN patients. This study aimed to investigate the relationship between immunosuppressive therapy and renal prognosis in PMN patients.MethodsThis was a real-world retrospective study including patients diagnosed with PMN in Shenzhen Second People’s Hospital and Hechi People’s Hospital. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival analysis were used.ResultsAfter propensity score-matching, 464 PMN patients were included and they were assigned to conservative and immunosuppressive group in a 1:1 ratio. Immunosuppressive therapy was the protective factor of renal composite outcome (HR = 0.65, p < 0.01). Separately, the effect was significant in moderate- and high-risk but not in low-risk patients. Key influencing factors including age, blood pressure, albumin and total cholesterol levels, with slight differences among patients at different risk.ConclusionsThis study demonstrates the efficacy of immunosuppressive therapy in non-low-risk PMN patients. The key factors affecting renal prognosis in patients with different risk levels are emphasized to help provide individualized treatment.