UNASSIGNED: This retrospective study aims to investigate the prevalence and immunopathologic characteristics of seropositive and seronegative hepatitis B virus-associated membranous nephropathy (HBV-MN).
UNASSIGNED: Clinicopathologic and serologic records of 420 patients with histologically confirmed HBV-MN between January 2014 and July 2021 were examined to determine the prevalence of seropositive and seronegative HBV-MN. Serum anti-PLA2R antibody testing was conducted on 280 patients with HBV-associated membranous nephropathy (HBV-MN) from August 2018 to July 2021. Immunopathologic characteristics of HBV-MN patients and anti-PLA2R antibody positivity were analyzed.
UNASSIGNED: Among 420 pathologically confirmed HBV-MN patients, 230 (54.8%) were seropositive for HBV. The seropositive group exhibited higher blood creatinine values and incidence of liver function abnormalities than the seronegative group (p < .05). Serum anti-PLA2R antibody testing on 280 HBV-MN patients revealed a total positive rate of 44.6%, with the seronegative group showing a significantly higher rate (62.6%) compared to the seropositive group (32.1%) (p < .01). The anti-PLA2R antibody-positive group displayed higher levels of urine protein (p < .05), serum cholesterol (p < .01), and IgG4 subtypes (p < .05) compared to the negative group. Additionally, the positive group had significantly lower levels of serum albumin and IgG than the negative group (p < .01).
UNASSIGNED: This comprehensive study reveals a significantly higher prevalence of seronegative HBV-MN than previously thought. The blood creatinine values and incidence of liver function abnormalities was higher in the serology-positive group than in the serology-negative group. Notably, the seronegative group displayed a higher positive rate of anti-PLA2R antibodies compared to the seropositive group, indicating distinctive clinical and immunopathologic features.

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.

UNASSIGNED: MicroFlow imaging (MFI) is a novel noninvasive ultrasound (US) technique that depicts microcirculatory blood vessels in the kidney while filtering out tissue motion and enhancing blood flow signals. We aimed to investigate the value of MFI for the detection of renal microvascular perfusion in chronic kidney disease caused by stage I-II membranous nephropathy (MN).
UNASSIGNED: Seventy-six participants including biopsy-proven MN (n=38) and healthy volunteers (n=38) were prospectively examined using MFI from March 2020 to December 2020. In addition, patients with MN were subdivided into a mild group, a moderate group, and a severe group based on the results of vascular pathology evaluation. All MFI images were analyzed by Image Pro Plus to obtain a cortical vascular index (VI). Basic patient information, relative US parameters and laboratory results were then acquired for each participant. Finally, after the univariate analysis among multiple groups, binary logistic regression (forward LR) and ordered logistic regression were used for multivariate analysis. Significance was set at P<0.05.
UNASSIGNED: VI was significantly lower in MN patients compared with that of healthy controls (0.65±0.09 vs. 0.35±0.18, P<0.001). After multivariate analysis, we found that the exploratory diagnostic performance of VI [area under the curve (AUC): 0.94; 95% confidence interval (CI): 0.89-0.99] outperformed that of serum creatinine (Scr) (AUC: 0.87; 95% CI: 0.79-0.95) in identifying MN. We also observed considerable differences among MN groups in parameters including VI (P=0.006), estimated glomerular filtration rate (eGFR) (P=0.037), shape (P=0.013), and impression (P=0.007). In addition, in the group with mild vascular damage, the exploratory diagnostic performance of VI (AUC: 0.79; 95% CI: 0.64-0.94) was better than other parameters, such as eGFR (AUC: 0.63; 95% CI: 0.43-0.84).
UNASSIGNED: MFI detected abnormal renal microvascular perfusion in patients with MN (particularly in those with early vascular damage or preserved renal function) without the use of a contrast agent. Combining MFI with B-mode US can improve the predictive performance of traditional kidney US.

UNASSIGNED: Primary glomerular disease accounts for one-sixth of all chronic kidney diseases (CKDs) in India. We remain limited in our ability to effectively treat these conditions because of lack of understanding of the disease mechanisms and lack of predictors to identify the clinical course and therapeutic responsiveness. We propose to develop a network of investigators in glomerular diseases, collect information in a systematic fashion to understand the clinical outcomes, answer translational research questions better, and identify and recruit patients for clinical trials.
UNASSIGNED: This is a prospective, observational study. The Indian TrANslational GlomerulonephrItis BioLogy nEtwork (I-TANGIBLE) cohort will enroll patients (>18 years) with biopsy-proven minimal change disease (MCD), focal segmental glomerulonephritis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), or membranoproliferative glomerulonephritis (MPGN) (immune complex- and complement-mediated), with first biopsy taken within 2 years of enrollment. Patients with estimated glomerular filtration (eGFR) rate <15 ml/min/1.73 m2 for >3 months at the time of screening, kidney transplant or bone marrow transplant recipients, patients with active malignancy, and patients with active hepatitis B/C replication or human immunodeficiency virus (HIV)-I/II will be excluded. Clinical details including history, medication history and details, and family history will be obtained. Consenting patient\'s blood and urine samples will be collected and stored, aligned to their clinical follow-up.
UNASSIGNED: The network will allow accurate ascertainment of disease burden of glomerular diseases across study sites, establishment of the treatment pattern of common glomerular diseases, investigation of medium- and long-term outcomes (remission, relapse, rate of eGFR decline), and building a suitable infrastructure to carry out clinical trials in primary glomerular disease.

Membranous nephropathy (MN) is a major pattern of nephrotic syndrome (NS) in adults. Some MN have secondary causes and some may be accompanied with other glomerular diseases. MN patients coexisting with amyloidosis are very rare, and mostly was polytypic MN. Herein, we describe the first report which identifying monotype PLA2R-MN (κ light chain) concurrent with leukocyte chemotactic factor 2 amyloidosis (ALECT2). This rare case highlights the importance of renal pathology for diagnosis.
We describe a case of a 60-year-old male patient with persistent proteinuria and low serum albumin for nine months. No monoclonal component was revealed by serum and urine immunofixation electrophoresis but serum PLA2R antibody was positive. The patient was empirically treated with Leflunomide and Losartan, but edema was not improved. The diagnosis of renal pathology is PLA2R-related monotypic (IgG-κ positive) MN concurrent with ALECT2. Methylprednisolone, cyclosporine A and anticoagulant (rivaroxaban) were prescribed resulting in a complete remission of NS.
MN patients concurrent with ALECT2 presented massive proteinuria or NS. When nephrotic range proteinuria is present in ALECT2, it is important to consider that it may be due to a concomitant underlying nephropathy especially MN and treated according to MN will get good therapeutic effect.

BACKGROUND: Membranous nephropathy is a glomerular disease characterized by the presence of immune-complexes deposited in the subepithelial space of the glomerular basement membrane. It is the main cause of nephrotic syndrome in adults, while in children it is very infrequent. Anti-CD20 monoclonal antibodies, mainly rituximab, represent a specific treatment for this disease.
METHODS: We report the case of a child presenting at 2 years of age with steroid-resistant nephrotic syndrome diagnosed upon kidney biopsy as semaphorin 3B (SEMA3B)-associated primary membranous nephropathy. The patient responded to treatment with cyclosporine, but invariably relapsed upon tapering of this agent. Therefore, at age 9, he was successfully treated with rituximab to overcome cyclosporine dependence. However, after the second rituximab infusion, a rapid reconstitution of CD19 + B cells and a relapse of proteinuria occurred, requiring reintroduction of cyclosporine. Obinutuzumab, a type II anti-CD20 monoclonal antibody, was then infused inducing prolonged CD19 + B cell depletion and remission of proteinuria despite discontinuation of cyclosporine. A greater reduction in circulating anti-SEMA3B antibodies assessed by Western blot was observed after obinutuzumab compared with rituximab infusion.
CONCLUSIONS: Obinutuzumab was safe and well-tolerated, and may therefore represent an effective therapeutic alternative in children with primary MN and rituximab resistance.

BACKGROUND: Chylothorax is a state in which pleurisy is induced by chylomicron leakage due to lymphatic injury. Membranous nephropathy (MN) is one of the relatively common glomerular diseases that cause nephrotic syndrome in adults. Chylothorax at the onset of nephrotic syndrome is very rare in adult patients.
METHODS: We report a case of chylothorax associated with primary MN. A 64-year-old man visited the hospital complaining of lower extremity edema and dyspnea for 4 weeks. Laboratory findings showed no azotemia but hypercholesterolemia, hypoalbuminemia, nephrotic-range proteinuria, and microscopic hematuria. Chest and abdominal computed tomography (CT) revealed no ascites, venous thrombosis, or malignancy with the presence of right-side pleurisy. Biochemical analysis of the pleural fluid was consistent with chylothorax. The patient was confirmed to have MN by percutaneous kidney biopsy. An angiotensin receptor blocker, diuretics, and a hypolipidemic agent were prescribed; non-per os, total parenteral nutrition (TPN), and subcutaneous injection of octreotide were added for management of chylothorax. As serum anti-phospholipase receptor 2 antibody (Ab) concentration increased again, immunosuppressive therapy (IST) consisting of alternating monthly cycles of glucocorticoids and oral cyclophosphamide was instituted. With no improvement in chylothorax and deteriorating nutritional status despite 3 weeks of medical therapy, lymphangiography was performed, followed by thoracic duct embolization (TDE). The patient was discharged from the hospital on day 53 with clinical improvement. At 9 months after discharge, clinical remission of primary MN was achieved without recurrence of chylothorax.
CONCLUSIONS: Patients with nephrotic syndrome may rarely exhibit refractory chylothorax without chylous ascites, increasing the risk of serious metabolic complications such as severe malnutrition. Therefore, upon confirming chylothorax associated with primary nephrotic syndrome, prompt radiologic intervention for lymphatic leakage must be considered in addition to specific IST.

Idiopathic membranous nephropathy is the main cause of chronic kidney disease (CKD). Studies have shown sodium-glucose co-transporter 2 (SGLT2) inhibitors significantly delay renal outcomes in patients with CKD, but the exact mechanism remains unknown. In this study, we investigated the mechanism by which the SGLT2 inhibitor canagliflozin attenuates podocyte injury by reversing the imbalance in Helper T cell 1 (Th1)/Helper T cell 2 (Th2) in peripheral blood of rats with membranous nephropathy (MN). MN rats were gavaged with canagliflozin (10 mg/kg/d) and losartan (10 mg/kg/d), respectively, for eight weeks. Compared with the MN group, the urinary ratio of total protein and the creatinine levels of the canagliflozin group decreased significantly. Canagliflozin improved the glomerulus pathological damage, increased the expression levels of podocyte marker proteins. The protective effect of canagliflozin on kidneys was more obvious than that of losartan. Treatment with canagliflozin increased the proportion of Th1 cells by 2.3 times, decreased the proportion of Th2 cells by 68.5%, and significantly restrained the synthesis of immunoglobulin G1 in B-cells and glomerulus subepithelial immune complex deposition. Co-culture of B-cells derived from MN rats with podocytes triggered the activation of phosphorylation of mTOR and ULK1 of podocytes, inhibited podocyte autophagy and resulted in podocyte injury. B-cells derived from canagliflozin treatment rats reversed these effects above. In conclusion, canagliflozin exerts a protective effect on kidneys by reversing the imbalance in Th1/Th2 cells in MN rats and restoring the autophagy of podocytes inhibited by the abnormal immunoglobulin G secretion from B-cells.

UNASSIGNED: Membranous nephropathy (MN) is the pathology type with the highest incidence of thrombotic events in nephrotic syndrome (NS). While patients with MN are prone to developing thromboembolic complications, the specific mechanism remains unclear. Many studies have shown a high titer of PLA2R antibody aggravates proteinuria and hypoalbuminemia and predicts a lower likelihood of clinical remission in patients with PLA2R-associated MN. Proteinuria and hypoalbuminemia also increase the risk of thrombotic events. In our previous review, we found secretory phospholipase A2 (sPLA2) may act as a ligand for PLA2R, and binding of sPLA2 to PLA2R results in damage to podocytes. sPLA2 can promote the release of AA from membrane phospholipids, and AA is closely related to blood lipid levels and coagulation cascades. The objective of this study is to explain the relationship between phospholipase A2 receptor (PLA2R) and blood hypercoagulability in MN patients and the new theory that secretory phospholipase A2 (sPLA2) and arachidonic acid (AA) may play a role in regulating blood lipid levels and the coagulation cascade in patients with PLA2R-positive MN.
UNASSIGNED: Literature retrieval was conducted through China National Knowledge Infrastructure (CNKI) and PubMed. Abstract and Introduction information was then retrieved and the results from the literature searched, classified, and important information summarized. A conclusion was then reached, and a new standpoint put forward.
UNASSIGNED: We discussed the role of PLA2R antibody and sPLA2 in hypercoagulability in patients with MN and analyzed the following four possible mechanisms: sPLA2 can combine with PLA2R and induce podocyte apoptosis; sPLA2 may promote the production of anti-PLA2R antibodies; sPLA2 may promote the release of AA from membrane phospholipids; and AA induces platelet aggregation.
UNASSIGNED: PLA2R may exacerbate hypercoagulability in patients with PLA2R-related MN, and sPLA2 plays an important role in the process.

Diagnosing immune checkpoint inhibitor (ICI)-associated nephritis can be challenging since it is a rare complication of therapy, associated with a spectrum of immune-mediated pathologies, and can present months after ICI therapy discontinuation (i.e., late-onset). ICIs are increasingly administered in combination with other cancer therapies with associated nephrotoxicity, further obfuscating the diagnosis of ICI-associated nephritis. In this report, we describe the first suspected case of late-onset ICI-associated membranous nephropathy (MN) in a patient with metastatic clear cell renal cell carcinoma (RCC) who had discontinued ICI therapy 6 months prior to presentation. Prompt recognition of the suspected late-onset immune-related adverse event (irAE) resulted in the successful treatment of MN and continuation of RCC therapy.
A 57-year-old man with metastatic clear cell RCC was responsive to third-line RCC therapy with lenvatinib (oral TKI) and everolimus (oral mTOR inhibitor) when he presented with nephrotic range proteinuria and acute kidney injury (AKI). His kidney biopsy revealed probable secondary MN with subendothelial and mesangial immune complex deposits and negative staining for both phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A). While a diagnosis of paraneoplastic MN could not be excluded, the patient was responding to cancer therapy and had tumor regression. However, 6 months prior to presentation, the patient had received pembrolizumab, an ICI, with his first-line RCC treatment. Due to concern that the patient may be presenting with late-onset ICI-associated MN, he was effectively treated with rituximab, which allowed for his continued RCC therapy.
This report highlights the first case of suspected late-onset ICI-associated MN and the increasing complexity of recognizing renal irAEs. With the growing indications for the use of ICIs in combination with other cancer therapies, recognizing the various presentations of ICI-immune nephritis can help guide patient management and treatment.