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

BACKGROUND: 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. METHODS: 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 24 months. The secondary outcomes were the relapse and safety evaluation. RESULTS: 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 24 months 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 6 months and maintained through to the second year. No significant difference in the occurrence of total side effects between the two groups (p = .160). CONCLUSIONS: 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 2 years. RTX appeared to have benefits in terms of prolonging relapse-free survival.

Observational study of immunosuppressive treatment patterns and outcomes in primary membranous nephropathy: a multicenter retrospective analysis.

BACKGROUND: We evaluated the efficacy of different immunosuppressive regimens in patients with primary membranous nephropathy in a large national cohort. METHODS: In this registry study, 558 patients from 47 centers who were treated with at least one immunosuppressive agent and had adequate follow-up data were included. Primary outcome was defined as complete (CR) or partial remission (PR). Secondary composite outcome was at least a 50% reduction in estimated glomerular filtration (eGFR), initiation of kidney replacement therapies, development of stage 5 chronic kidney disease, or death. RESULTS: Median age at diagnosis was 48 (IQR: 37-57) years, and 358 (64.2%) were male. Patients were followed for a median of 24 (IQR: 12-60) months. Calcineurin inhibitors (CNIs) with or without glucocorticoids were the most commonly used regimen (43.4%), followed by glucocorticoids and cyclophosphamide (GC-CYC) (39.6%), glucocorticoid monotherapy (25.8%), and rituximab (RTX) (9.1%). Overall remission rate was 66.1% (CR 26.7%, PR 39.4%), and 59 (10.6%) patients reached secondary composite outcome. Multivariate logistic regression showed that baseline eGFR (OR 1.011, 95% CI: 1.003-1.019, p = 0.007), serum albumin (OR 1.682, 95% CI: 1.269-2.231, p < 0.001), and use of RTX (OR 0.296, 95% CI: 0.157-0.557, p < 0.001) were associated with remission rates; whereas only lower baseline hemoglobin was significantly associated with secondary composite outcome (OR: 0.843, 95% CI: 0.715-0.993, p = 0.041). CYC use was significantly associated with higher remission (OR 1.534, 95% CI: 1.027-2.290, p = 0.036). CONCLUSIONS: Higher baseline eGFR and serum albumin levels correlated with increased remission rates. Remission rates were lower in patients treated with RTX, while those on GC-CYC showed higher rates of remission. Due to the study's retrospective nature and multiple treatments used, caution is warranted in interpreting these findings.

A noninvasive method of diagnosing membranous nephropathy using exosomes derived from urine.

Background: Membranous nephropathy (MN) is a specific autoimmune disease affecting kidneys. It is characterized by the accumulation of immune complexes in the glomerular basement membrane. Renal biopsy is currently the standard procedure to confirm the diagnosis, although the presence of autoantibodies against the phospholipase A2 receptor (PLA2R) can also help diagnose. In this study, we aimed to investigate the potential of urinary exosomes as noninvasive markers for diagnosing MN. Methods: Exosomes were extracted from urine samples of five patients with MN and four healthy controls. The concentration of PLA2R was measured in both urine and isolated exosomes using enzyme-linked immunosorbent assay techniques. The measurements were adjusted based on the urine creatinine (UCr) level of each participant. Results: The levels of PLA2R/UCr were investigated in urine and urine-derived exosomes from patients and controls. Results of the analysis revealed significantly higher expression of PLA2R/UCr in patients compared to the control group (p < 0.05). Furthermore, the expression level of PLA2R/UCr was higher in urine-derived exosomes than in urine samples. Additionally, a positive correlation was observed between the expression levels of PLA2R/UCr and the urine protein-to-creatinine ratio, with urine-derived exosomes exhibiting a stronger correlation than urine samples. Conclusion: Studies have indicated that measuring exosomal PLA2R/UCr levels in urine could be a noninvasive method for diagnosing MN. Using urine-derived exosomes could also reduce the burden of performing a biopsy on patients and facilitate follow-up treatment, such as monitoring for future recurrence.

Nerve Epidermal Growth Factor-Like 1 Protein (NELL-1) Expression in Mercury-Related Membranous Nephropathy: Is It a True Association or a Chance Occurrence?

Background: Neural epidermal-like growth factor-like 1 (NELL-1) is a protein kinase C binding protein expressed in osteoblasts and renal tubules. It is expressed in 5%-25% glomerular cells at the mRNA level. Membranous Nephropathy (MN) is characterized by the presence of antibodies against certain types of antigens on the glomerular basement membrane. The most common one implicated in primary MN is an antibody against PLA2R. Many newer antigens have been discovered in the recent past, which are proven to cause secondary MN, one of which is NELL-1. NELL-1 has been associated with malignancy-associated MN and also recently associated with traditional indigenous medications containing mercury. In this study, we study the expression of NELL-1 in mercury-associated MN. Materials and Methods: Records of ten cases of Mercury -associated MN were retrieved from the Institute medical archives and NELL-1 Immunohistochemistry was performed in all ten cases. Results: NELL-1 was found to be positive in 50% of the cases of Mercury associated MN. In addition, mass spectrometric studies was performed, which revealed the common Mercuric compound associated to be 'Swaskalpa', 'Sudarshana Melugu' and 'Rasagandhi Mezhugu'. Conclusion: This study highlights why it is important to diagnose mercury-associated MN by a pathologist by picking up the finer histopathological clues and by using NELL-1 immunohistochemistry, especially in PLA2R-negative patients. The former is true as most of the time a history of mercuric compound intake is missed out.

Causality between diabetes and membranous nephropathy: Mendelian randomization.

BACKGROUND: Membranous nephropathy (MN) has not yet been fully elucidated regarding its relationship with Type I and II Diabetes. This study aims to evaluate the causal effect of multiple types of diabetes and MN by summarizing the evidence from the Mendelian randomization (MR) study. METHODS: The statistical data for MN was obtained from a GWAS study encompassing 7979 individuals. Regarding diabetes, fasting glucose, fasting insulin, and HbA1C data, we accessed the UK-Biobank, within family GWAS consortium, MAGIC, FinnGen database, MRC-IEU, and Neale Lab, which provided sample sizes ranging from 17,724 to 298,957. As a primary method in this MR analysis, we employed the Inverse Variance Weighted (IVW), Weighted Median, Weighted mode, MR-Egger, Mendelian randomization pleiotropy residual sum, and outlier (MR-PRESSO) and Leave-one-out sensitivity test. Reverse MR analysis was utilized to investigate whether MN affects Diabetes. Meta-analysis was applied to combine study-specific estimates. RESULTS: It has been determined that type 2 diabetes, gestational diabetes, type 1 diabetes with or without complications, maternal diabetes, and insulin use pose a risk to MN. Based on the genetic prediction, fasting insulin, fasting blood glucose, and HbA1c levels were not associated with the risk of MN. No heterogeneity, horizontal pleiotropy, or reverse causal relationships were found. The meta-analysis results further validated the accuracy. CONCLUSIONS: The MR analysis revealed the association between MN and various subtypes of diabetes. This study has provided a deeper understanding of the pathogenic mechanisms connecting MN and diabetes.

Exploring PLA2R and HLA in membranous nephropathy: A narrative review of pathogenic mechanisms and emerging therapeutic potentials.

Membranous Nephropathy (MN), a non-inflammatory autoimmune glomerulopathy, is a prominent cause of nephrotic syndrome, predominantly affecting Caucasian adults. It is characterized by significant thickening of the glomerular basement membrane, a direct result of immune complex deposition. Fundamental to its pathogenesis are the Phospholipase A2 receptor (PLA2R) and Human Leukocyte Antigens (HLA), which play crucial and interconnected roles. Specifically, PLA2R serves as the primary antigen, while HLA molecules facilitate MN-specific immune responses, thereby providing key insights into the disease's etiology. This study critically examines the roles of PLA2R and HLA in MN, with a particular focus on the antigenic epitopes of PLA2R. Given MN's complex nature, personalized therapeutic interventions are essential. Accordingly, targeting immunogenic epitopes has emerged as a transformative approach, aimed at modulating specific immune responses without disrupting overall immune function. Numerous studies and clinical trials have been advancing the application of these epitopes in therapeutic strategies. Nevertheless, challenges such as identifying effective epitopes, enhancing epitope-specific responses, and optimizing therapeutic dosing remain. This narrative review addresses these challenges in depth, offering a comprehensive insight into the pathology and emerging treatment strategies for MN.

Obinutuzumab versus rituximab for the treatment of refractory primary membranous nephropathy.

BACKGROUND: Rituximab has been shown effective in patients with primary membranous nephropathy refractory to glucocorticoids plus cyclophosphamide (GC+CTX) or calcineurin inhibitors (CNIs), but the response rates remain limited. Compared with rituximab, obinutuzumab is a humanized anti-CD20 monoclonal antibody with greater B-cell depletion capacity. This study was performed to investigate the effectiveness of obinutuzumab compared to rituximab in treating patients with refractory primary membranous nephropathy. METHODS: A retrospective study was conducted at Huashan Hospital, Fudan University between January 1, 2015 and July 31, 2024, and included adult patients with primary membranous nephropathy who met the following criteria, 1) resistance to GC+CTX and/or calcineurin inhibitor (CNI) regimens, 2) dependence on CNIs, or 3) relapse within 1 year after CTX discontinuation. The patients subsequently received either obinutuzumab or rituximab. The primary endpoint was treatment response, which was defined as overall remission of nephrotic syndrome with no need for rescue therapy after obinutuzumab versus rituximab treatment. The secondary measures included immunological remission and safety profiles. RESULTS: Among the 51 participants, 20 received obinutuzumab and 31 received rituximab. The response rate was significantly greater in patients receiving obinutuzumab than in those receiving patients (90.0% vs. 38.7%, p<0.001) during a follow-up period of 24 (IQR, 10-34) months. Cox proportional hazards survival regression analysis also revealed the superior effectiveness of obinutuzumab (p<0.001). Immunological remission rates were higher in patients receiving obinutuzumab at both 3 months (75.0% vs. 20.0%, p<0.001) and 6 months (87.5% vs. 21.4%, p<0.001). The safety profiles of the two treatments were comparable. Among the 19 nonresponders treated with rituximab, 10 subsequently received obinutuzumab, and 8 achieved remission during a follow-up period of 20.0 (IQR, 18.5-22.3) months. CONCLUSION: This retrospective study suggests that obinutuzumab is an effective treatment option for patients with primary membranous nephropathy refractory to GC+CTX, CNI, and rituximab regimens.

NELL-1 membranous nephropathy due to mercury exposure from fairness cream: Report of two cases.

Mercury contained in beauty-enhancing cosmetics can cause chronic poisoning and membranous nephropathy (MN). We report two cases of nephrotic syndrome caused by MN with evidence of mercury poisoning due to the application of fairness cream in a short duration of a few months. The individuals were positive for neural epidermal growth factor-like 1 [NELL-1]. Discontinuation of the use of cosmetic products and modified Ponticelli regimen improved the nephrotic state in these individuals. We suggest that mercury poisoning should be considered in NELL-1-positive individuals with a history of application of beauty products.

The outcomes of primary membranous nephropathy treated with cyclophosphamide are superior to calcineurin inhibitors in patients with renal vascular lesions: A multi-center retrospective cohort study.

BACKGROUND: The difference of the outcomes of primary membranous nephropathy (PMN) with renal vascular lesions treated with cyclophosphamide (CTX) compared to calcineurin inhibitors (CNIs) remains undetermined. METHODS: 872 patients with PMN finished CNIs or CTX-based therapy between 2003 and 2018 from three centers in China were followed up at most to 120 months. A propensity-score matched (PSM) method was used to analyze the difference of outcomes between those receiving CTX- and CNIs-based therapy. Primary endpoints were defined as a composite of a 50 % decline in eGFR, progression to end-stage renal disease, or all-cause mortality. Dual immunohistochemical staining of CD31 and α-smooth muscle action were applied to detect pathological vascular lesions. RESULTS: A total of 761 patients were included in the study. After PSM, no significant difference of proteinuria complete remission rate was found between 126 paired patients (HR, 1.32; 95 % CI, 0.95 to 1.83; p = 0.10). However, CTX-based therapy was associated with significantly better renal survival compared to CNI-based therapy. (median, 156 months vs. 108 months; hazard ratio [HR], 0.31; 95 % confidence interval [CI]0.16 to 0.61; p = 0.001). Subgroup analyses showed that CTX-based therapy was superior to CNIs-based therapy among patients with hyalinosis damage (HR, 0.16; 95 % CI 0.05 to 0.50; p = 0.002;), arteriosclerosis (HR, 0.31; 95 % CI 0.15 to 0.62; p = 0.001), or hypertension (HR, 0.21; 95 % CI 0.08 to 0.53; p = 0.001). CONCLUSIONS: CTX-based therapy exhibited a significantly improved composite endpoint of PMN patients with vascular lesions compared to CNIs-based regime.

Villous Adenoma: A Rare Cause of Neural Epidermal Growth Factor-Like 1-Positive Membranous Nephropathy.

We report the case of a 70-year-old woman diagnosed with neural epidermal growth factor-like 1 antigen-positive membranous nephropathy and nephrotic syndrome. Following thorough exclusion of autoimmune diseases, medications, or infections as potential causes, colonoscopy was performed as part of malignancy evaluation, revealing an 18 mm villous adenoma in the sigmoid colon and a 7 mm tubulovillous adenoma in the cecum. Despite the absence of gastrointestinal symptoms initially and the absence of high-grade dysplasia in the pathology report, the patient experienced a remarkable improvement in symptoms and a reduction in nephrotic-range proteinuria following polypectomy, observed within a few months.

Phospholipase A2 receptor-negative membranous nephropathy presenting as a rare renal manifestation of IgG4-related disease.

IgG4-related disease is a fibroinflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells affecting multiple organs. Though the most common renal manifestation of IgG4-related disease is tubulointerstitial nephritis, it can rarely present as secondary membranous nephropathy. We present a case of a 75-year-old male with phospholipase A2 receptor-negative membranous nephropathy as an atypical manifestation of IgG4-related disease. The patient presented with nephrotic syndrome and was found to have elevated serum IgG4 levels and IgG4-positive plasma cells in the kidney biopsy. He was successfully treated with corticosteroids and rituximab, resulting in significant improvement in proteinuria and normalization of IgG4 levels. This case highlights the importance of considering IgG4-related disease in patients with phospholipase A2 receptor-negative membranous nephropathy, especially in those with a history of other organ involvement. Early recognition and treatment of IgG4-related disease are crucial to prevent progressive kidney damage and improve patient outcomes.

A Case of Tiopronin-induced Membranous Nephropathy Presenting with IgG4-predominant Staining Pattern.

Tiopronin is a key drug used to treat cystinuria. A 41-year-old Japanese woman with cystinuria presented with eyelid edema and weight gain after the administration of tiopronin. Her serum albumin was 1.8 g/dL and her urinary protein level was 5.5 g/gCre. After cessation of tiopronin, she achieved remission of nephrotic syndrome (NS). Secondary NS due to tiopronin was evident based on the clinical course and laboratory values. A kidney biopsy showed membranous nephropathy (MN), and an immunofluorescence analysis revealed strong deposition of immunoglobulin G4 (IgG4). However, a previous case report of tiopronin-induced MN showed staining for IgG1 and IgG3. This case report suggests a novel etiology for tiopronin-induced MN.

How Stem and Progenitor Cells Can Affect Renal Diseases.

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

From Diagnosis to Dialysis: Managing Primary Membranous Nephropathy in a Patient Living With Human Immunodeficiency Virus (HIV).

Membranous nephropathy (MN) is a significant cause of nephrotic syndrome in adults, with both primary and secondary etiologies contributing to its pathogenesis. This case report explores the clinical course of a 69-year-old African American man with human immunodeficiency virus (HIV) who developed primary MN, progressing to end-stage renal disease (ESRD) despite treatment efforts. Initially diagnosed with IgA nephropathy and HIV-associated immune complex kidney disease (HIVICK), the patient later developed anti-phospholipase A2 receptor (anti-PLA2R) antibody-positive MN. Despite immunosuppressive therapy and partial remission with rituximab, non-adherence to treatment led to disease exacerbation and eventual hospitalization for acute heart failure and worsening renal function. A subsequent renal biopsy revealed severe interstitial fibrosis and tubular atrophy, limiting further therapeutic options. This case underscores the challenges in managing MN, particularly in high-risk patients with comorbidities such as HIV, and highlights the importance of adherence to treatment and tailored management strategies to optimize outcomes in this complex condition.

Bibliometric and visual analysis of membranous nephropathy literature from 2010 to 2023.

Background: Membranous glomerulonephritis, also known as membranous nephropathy (MN), is a common cause of nephrotic syndrome in adults. Despite extensive research on MN, bibliometric studies on the subject are scarce. Therefore, this study aimed to provide a visual analysis of global trends in membranous nephropathy research over the past 13 years. Methods: This study conducted a bibliometric and visual analysis of global trends in MN research from 2010 to 2023. Articles related to MN were retrieved from the Web of Science Core Collection (WoSCC) database. Tools such as CiteSpace and VOSviewer were utilized to analyze publications, countries, institutions, authors, publishing journals, co-cited references, and keywords to identify the current state and future trends in MN research. Results: The analysis encompassed 1,624 publications, showing an annual increase from 2010 to 2023. The People's Republic of China emerged as the most active country in this field, while France's Sorbonne Universite and Institut National de la Sante et de la Recherche Medicale (Inserm) led in publication volume among academic institutions. Debiec Hanna stood out as the most prolific author. BMC Nephrology had the highest number of publications, making it the most favored journal in the field. The article with the greatest co-citation intensity was "Primary Membranous Nephropathy," a review published in 2017. Conclusion: This study shows that there has been increasing interest in membranous nephropathy over the past 13 years. The most frequently encountered keywords were "membranous nephropathy" "nephrotic syndrome," and "glomerulonephritis." Analysis of emerging terms indicated that "a2 receptor antibody," "domain containing 7a," and "t cell" may remain prominent subjects of research in the forthcoming years. The findings highlight key research trends and areas of interest that can inform researchers, clinicians, and policymakers about the current state of MN research and help guide future research directions and clinical practice.

Characteristics of anti-contactin1 antibody positive autoimmune nodopathies combined with membranous nephropathy.

BACKGROUND: Autoimmune nodopathy (AN) is a very rare new disease entity, especially when combined with membranous nephropathy (MN). METHODS: Antibodies against nodal-paranodal cell adhesion molecules in the serum were detected using cell-based assays. Antibody subtypes against contactin-1 (CNTN1) were confirmed. Cases of anti-CNTN1 antibody-positive AN with and without MN were retrieved through a literature search to compare clinical and electrophysiological characteristics. RESULTS: A 65-year-old male patient with MN developed limb numbness and weakness, along with walking instability. Serum CNTN1 antibodies were positive, primarily those of the IgG4 subtype. Electromyography showed prominent demyelination patterns in both the proximal and distal segments of the nerves compared to the middle nerve trunk. Magnetic resonance imaging revealed enlargement of the bilateral brachial and lumbosacral plexuses and local hyperintensity of the right C5-C6 nerve roots. Thirty-five cases with anti-CNTN1 antibody-positive AN with MN and 51 cases with anti-CNTN1 antibody-positive AN without MN were compared. Furthermore, the proportion of patients with MN combined with AN presenting with acute or subacute onset was higher than that observed in the MN without AN group. Nevertheless, no substantial differences were noted between the two groups concerning the clinical and electrophysiological characteristics, which were mainly elderly men, manifested as sensory ataxia, IgG4 antibody subtype, electrophysiological demyelination, and a certain effect on immunotherapy. CONCLUSION: In cases of electrophysiological manifestation of demyelinating peripheral neuropathy, especially in distal and poximal segments of nerves, AN should be considered, and further screening for renal function should be performed. Concomitant MN does not aggravate or alleviate peripheral nerve symptoms.

Therapeutic targets in membranous nephropathy: plasma cells and complement.

Membranous nephropathy (MN) is an antibody-mediated autoimmune disease and the most common cause of nephrotic syndrome in adults. The discovery of phospholipase A2 receptor 1 (PLA2R1) as the first target antigen in patients with MN 15 years ago has led to a paradigm shift in the pathobiological understanding of this disease. Autoantibodies against PLA2R1 as well as thrombospondin type-1 domain-containing 7A, the second identified antigen in adults, were shown to be disease-causing and act through local activation of the complement system, primarily via the classical and lectin pathways. These findings indicate that both plasma cells, the main source of antibodies and autoantibodies, as well as the complement system, the main pathogenic effector mechanism in MN, are rational and pathogenesis-based treatment targets in MN. This review summarizes pathomechanistic and clinical evidence for and against plasma cell- and complement-targeted treatments in MN.

Complement Receptor 1 Enhancement in Recurrent Membranous Nephropathy Following Kidney Transplantation: A Case Report.

Membranous nephropathy (MN) recurs in some kidney allograft patients, and recurrence increases graft failure rates. We present a unique case of recurrent MN in first and second allografts showing glomerular capillary wall-positivity for complement receptor 1 (CR1) consistent with immunoglobulin G (IgG). A man in his late 20s developed MN and started hemodialysis. MN recurred and caused graft loss after the first transplantation and recurred again soon after the second transplantation. The IgG subclass staining was almost consistently negative for IgG4 and phospholipase A2 receptor (PLA2R)-staining was negative. Recurrent MN of unknown etiology was considered. Mass spectrometry demonstrated that CR1 had increased in the transplanted kidney biopsies. Immunohistochemistry and immunofluorescence studies demonstrated CR1 colocalized with IgG along glomerular capillaries in this case, whereas CR1 was localized in podocytes with no colocalization of IgG in a control case of PLA2R-associated MN. Correlative light and immunoelectron microscopy showed localization of CR1 at the interface between electron-dense deposits and podocytes. Collectively, this case demonstrated a unique enhancement and localization of CR1. MN with enhancement of CR1 has not been reported to date. CR1 may be a candidate causative antigen in this case of recurrent MN, although further study is needed to investigate the pathogenesis of CR1.

Efficacy and safety of rituximab in patients with PLA2R associated membranous nephropathy and resolved HCV infection.

Rituximab occasionally induces reactivation of hepatitis C virus (HCV) in patients with resolved HCV infection, sometimes with fatal consequences. As rituximab has become one of the first-line therapies for the treatment of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) and is more widely used, there is a lack of studies reporting the effectiveness and safety of rituximab in patients with PLA2R-associated MN and resolved HCV infection. A single-center retrospective study was conducted on PLA2R-associated membranous nephropathy (MN) patients who were HCVAb positive but HCV-RNA negative and treated with rituximab. A total of 598 adult patients with PLA2R-associated MN who underwent rituximab therapy were screened. General clinical information, including gender, age, pathological data, and previous treatment plans, was collected from medical records. Routine blood tests, liver and kidney function assessments, blood lipid profiles, 24-h urine protein levels, anti-PLA2R antibody titers, circulating B-cell counts, and HCV viral loads were measured at the time of rituximab infusion and repeated at intervals of 1-3 months post-rituximab administration. A total of 8 patients were enrolled, with a median follow-up period of 19.00 (range: 16.00-25.25) months. Among the 8 patients, 5 were male, and the mean age was 50.13 ± 4.29 years. Histological findings indicated that tubuloreticular inclusions, mesangial deposits, intramembranous deposits, and subendothelial deposits were not observed in any of the 8 patients. The overall 1-year remission rate for these patients was 75%, accompanied by a significant reduction in proteinuria. Additionally, blood albumin levels increased significantly, and renal function remained stable. No increase in HCV viral load and stable liver function tests were observed throughout the entire follow-up period. This study suggested that on the basis of successful eradication of HCV virus with antiviral drugs, rituximab can effectively induce clinical remission of patients with PLA2R associated MN and resolved HCV infection, and does not lead to a significant increase in HCV virus load. However, this finding is based on a very small sample size and should be confirmed in larger clinical trials.

De novo and recurrent post-transplant membranous nephropathy cases show similar rates of concurrent antibody-mediated rejection.

Background: Membranous nephropathy (MN) can develop post-kidney transplant and is classified as a recurrent disease in patients with a history of MN in the native kidneys or as de novo disease in patients without such history. The mechanism of recurrent MN is thought to be like that of primary MN, but the mechanism of de novo MN is not well delineated. An association between de novo MN and antibody-mediated rejection (AMR) has been suggested. Methods: A search of the pathology database from our medical center identified 11 cases of recurrent and 15 cases of de novo MN, in which clinical and histologic findings were compared. No significant differences were identified in the demographic characteristics, serum creatinine and proteinuria trends, or rates of allograft failure between the recurrent and de novo MN groups. Results: Rates of concurrent AMR were high in both groups (36% and 40%, respectively) but not statistically different from each other. PLA2R immunofluorescence (IF) positivity was seen in 64% of recurrent MN cases compared to 33% of de novo MN cases, suggesting a higher incidence of PLA2R-positive de novo MN than previously reported. No significant histologic differences were identified in the initial biopsies from the two groups, except mean IgG intensity by IF was higher in the recurrent group, suggesting a higher load of immune complex deposits at diagnosis in this group. Conclusion: The findings do not provide support for a specific association between AMR and de novo MN, but whether there is a possible link between both forms of post-transplant MN and AMR remains an unanswered question.