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.

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.

Membranous nephropathy (MN) is an autoimmune condition that is a common cause of nephrotic syndrome in nondiabetic adults. In this study, we highlight a case of a 22-year-old male with a past medical history of arthrogryposis multiplex congenita (AMC) who initially presented with right flank pain and hematuria. Subsequent workup revealed significant proteinuria with biopsy-proven primary MN. Early detection of the disease is critical to establish treatment promptly and prevent complications such as those resulting from a hypercoagulable state.

Recently, several target antigens of membranous nephropathy (MN), such as phospholipase A2 receptor (PLA2R) and exostosin 1/exostosin 2 (EXT1/2), have been discovered. A 30-year-old woman was referred to our hospital with nephrotic range proteinuria and microscopic hematuria. She was first noted to have proteinuria before pregnancy, and her proteinuria worsened in the postpartum period. A renal biopsy showed MN. Immunofluorescence microscopy showed IgG, IgA, IgM, C3, C4, and C1q depositions in the mesangial area and glomerular capillary walls (GCWs). Regarding the IgG subclass, IgG1 and IgG3 were detected on glomeruli. Electron microscopy showed subepithelial electron-dense deposits (EDDs). EDDs were also detected in paramesangial and subendothelial areas. The diagnosis of membranous lupus nephritis (MLN) was suspected, but she did not fulfill the criteria for systemic lupus erythematosus. Neither anti-nuclear antibody nor hypocomplementemia were detected. We further evaluated glomerular EXT1/2 expressions, which were evident on GCWs. In addition, PLA2R was also detected on GCWs, although serum antibody for PLA2R was negative. She responded to immunosuppressive therapy with decreased proteinuria. In the present case, glomerular PLA2R expression implied the possibility of primary MN. However, pathological findings with a full-house staining pattern and glomerular EXT1/2 expressions were very similar to those of lupus-associated MN. Glomerular PLA2R expression appeared not to reflect immunocomplexes of PLA2R and autoantibody when considering the results for glomerular IgG subclass and the absence of serum anti-PLA2R antibody. Collectively, it is plausible that this was a case of a relatively young postpartum female who developed latent MLN rather than primary MN.

The coexistence of primary membranous nephropathy (PMN), immunoglobulin A nephropathy (IgAN), and diabetic nephropathy (DN) in the same patient has been a subject of clinical and pathological investigation, yielding inconclusive results. The limited availability of cases and resource materials has hindered a comprehensive understanding of this phenomenon. We present the case of a 70-year-old Saudi Arabian man diagnosed with type 2 diabetes mellitus and nephrotic syndrome. A kidney biopsy revealed the coexistence of PMN, IgAN, and DN. The patient presented with an unusual and rare combination of PMN, IgAN, and DN. To address his condition, the patient consented to rituximab therapy and planned follow-up with the kidney transplant team. However, before the first dose of rituximab could be administered, the patient experienced severe septic shock secondary to pneumonia, which tragically led to his demise. The simultaneous occurrence of PMN, IgAN, and DN represents a rare and scarcely documented condition. The purpose of this article is to report this exceptional case, emphasizing the significance of further research to deepen the understanding of the underlying pathology behind these concurrent renal disorders. This report aims to shed light on the complexities of managing such complex cases and advancing therapeutic approaches in the future.

The phospholipase A2 receptor (PLA2R) associated with membranous nephropathy (MN) is an organ-specific autoimmune disease associated with PLA2R and human leukocyte antigen (HLA) genes. Familial PLA2R-related MN is rarely reported. The combination of anti-GBM disease and MN has been well documented, though the mechanism behind it remains unclear.
We describe two siblings diagnosed with pathology-confirmed PLA2R-related MN 1 year apart. And one of the two siblings developed an anti-GBM disease. The high-resolution HLA typing showed identical alleles in both siblings, specifically heterozygotes of DRB1*15:01/*03:01.
We describe a familial case of PLA2R-related MN supporting the role of genetic factors that HLA-DRB1*15:01 and DRB1*03:01 predispose patients in the development of PLA2R-related MN in the Han Chinese population. The combination of MN and anti-GBM disease may also partially be associated with the same susceptible HLA allele DRB1*15:01.

Membranous nephropathy (MN) is an autoimmune disease resulting in nephrotic syndrome. Neural epidermal growth factor-like 1 protein (NELL-1) has been shown to cause a rare form of MN that is more likely to be associated with malignancy. We present a case of a 73-year-old female who was found to have a NELL-1-associated segmental MN. She presented complaining of generalized weakness, chills, and poor appetite, worsening over a one-week duration. Her kidney functions were noted to be markedly deranged, with a computed tomography scan of the abdomen showing evidence of chronic kidney disease. Further testing confirmed heavy proteinuria, although the etiology was still uncertain. A kidney biopsy revealed granular subepithelial immunoglobulin G deposits with subsequent immunohistochemical staining for NELL-1 antigen being positive. She improved with supportive care over the next few days. Despite an extensive workup, no underlying malignancy was found. NELL-1 is a rare yet recognized antigen target for the development of MN. Up to a third of patients with NELL-1-associated MN have associated cancer, thus requiring evaluation for underlying malignancy in this cohort.

Nephrotic syndrome is a condition characterized by proteinuria, hypoalbuminemia, edema, hyperlipidemia, and a hypercoagulable state. Nephrotic syndrome may lead to several complications, including, but not limited to, increased risk of infection, respiratory distress, and thromboembolism. There are several etiologies of nephrotic syndrome with various predisposing factors ranging from idiopathic, autoimmune diseases, infections (human immunodeficiency virus, hepatitis C virus, hepatitis B virus), drugs, and heavy metal poisoning. Here, we report the case of a 37-year-old male who presented with worsening exertional dyspnea and bilateral lower extremity swelling. He was found to have simultaneous multiple acute thromboses in both the venous and arterial systems in the setting of worsening renal function. Further investigation revealed that the patient had membranous nephropathy. Initiation of anticoagulation and immunosuppression made a significant difference in his survival. Vascular thromboembolic (VTE) complications may be the initial presentation that prompts patients with nephrotic syndrome to seek medical care. As such, clinicians must have a high index of suspicion in patients presenting with concurrent VTE and nephrotic-range proteinuria. In addition, given that treatment modalities for the various etiologies of nephrotic syndrome differ considerably, it is also essential to distinguish the type of nephrotic syndrome in a patient, which dictates the treatment algorithm.

Membranous nephropathy is a common form of glomerulonephritis typically presenting between 30 to 50 years of age with nephrotic range proteinuria, with one third of patients undergoing spontaneous remission, one third experiencing non-progressive CKD (Chronic Kidney Disease) while the remaining third progressing to ESRD (end stage renal disease).
METHODS: A 21-year old pregnant female developed massive proteinuria and hypoalbuminemia during first weeks of pregnancy and required intensive nephrological evaluation and treatment. Renal biopsy was performed, microscopic examination was consistent with Membranous Nephropathy and as anti-PLA2R antibodies tested positive, active disease was confirmed. The patient received an immunosuppressive treatment consisting of prednizone and cyclosporine A, enoxaparine was also implemented. In the follow up proteinuria and hypoalbuminemia decreased significantly, stable eGFR and anti-PLA2R (M-type phospholipaseA2 receptor) depletion were observed. C-section was performed at 31 weeks of gestational age due to premature rupture of membranes. The baby developed correctly, showed no signs of nephrotic syndrome. After delivery the mother\'s immunosuppressive treatment was continued.
CONCLUSIONS: Diagnostic algorithm of adult patients with nephrotic syndrome suggests that in cases positive for anti PLA2R antibodies one can diagnose idiopathic membranous nephritis (IMN) based on serological testing and desist kidney biopsy. An early immunosupressive treatment applied in described case confirms proper procedure.