Bullous systemic lupus erythematosus (BSLE) is a rare blistering manifestation of systemic lupus erythematosus (SLE), characterized by widespread tense bullae resulting from autoantibodies against type VII collagen. It is predominantly seen in women and is exceptionally rare in pediatric males. We report a case of a 14-year-old South Asian male with recurrent tense blisters over the trunk, face, extremities, palms, and mucosa, alongside systemic features including photosensitivity, arthralgia, oral ulcers, and significant renal involvement. Laboratory findings revealed proteinuria, hypoalbuminemia, low complement levels, and positive antinuclear antibodies. Skin biopsy revealed subepidermal blisters with neutrophilic infiltrates, and direct immunofluorescence (DIF) demonstrated linear IgG, IgA, IgM, and C3 deposition at the basement membrane. Renal biopsy revealed membranous glomerulonephritis along with positive DIF showing IgG and C3 deposition. Treatment with corticosteroids, dapsone, and mycophenolate mofetil led to significant clinical improvement. This case emphasizes the need for a high index of clinical suspicion in young males presenting with blistering dermatoses, as BSLE may serve as an early marker of active systemic disease, particularly lupus nephritis. BSLE is considered an important diagnostic red flag, especially in the pediatric population, because its appearance may signal active underlying systemic disease, as seen in our patient with lupus nephritis. Sudden development of widespread tense blisters may coincide with systemic disease flares. Early recognition and aggressive management with immunosuppressants, along with close renal monitoring and long-term follow-up, are essential to reduce irreversible cutaneous and renal complications.

Rituximab is an established therapy for primary membranous nephropathy, but anti-rituximab antibodies (ARA) have been associated with rituximab treatment failure. We report a 66-year-old woman with PLA2R-positive membranous nephropathy who developed ARA positivity and clinical features consistent with rituximab treatment failure, including B-cell reconstitution, undetectable serum rituximab levels, and worsening proteinuria despite declining anti-PLA2R antibody titers. Kidney biopsy confirmed stage III membranous nephropathy. She was subsequently treated with the humanized type II anti-CD20 antibody obinutuzumab, which induced complete depletion of circulating B cells, achieved therapeutic serum concentration, follow by both immunological and clinical remission within 8.5 months, despite persistent ARA positivity. This case suggests that obinutuzumab may be an effective rescue option after rituximab failure associated with ARA and underscores the importance of integrating therapeutic drug monitoring, ARA detection, and B-cell kinetics assessment in the management of refractory membranous nephropathy.

Membranous nephropathy (MN), an autoimmune glomerulopathy driven by podocyte antigens, is a leading cause of end-stage renal disease (ESRD). However, its pathogenic mechanisms remain incompletely understood. This knowledge gap results in significant physical and psychological burdens for patients worldwide and poses substantial challenges for clinical management. Current conventional treatments for MN are often associated with significant side effects and may not yield satisfactory outcomes. Therefore, the development of more efficacious and better-tolerated therapeutic strategies for MN is imperative. Given these clinical challenges, Traditional Chinese Botanical Medicine (CHMs), with their multi-component and multi-target characteristics, have emerged as a promising alternative or complementary therapeutic approach for MN. This review aims to summarize the evidence on the mechanisms and clinical efficacy of CHMs and their active metabolites in treating MN, drawing from findings reported in animal experiments, clinical trials, systematic reviews, and meta-analyses. It seeks to elucidate the potential advantages of CHMs in MN management and to provide a reference for future research in this field. Study design and methods: For this review, the following major academic research databases were consulted: PubMed, ResearchGate, Science Direct, and Web of Science. "Glomerulonephritis, Membranous [MeSH Terms] OR Extramembranous Glomerulopathy [Text Word] OR Membranous Glomerulonephropathy [Text word] OR Membranous Nephropathy [Text word] OR Idiopathic Membranous Glomerulonephritis [Text word]OR Glomerulonephritides, Idiopathic Membranous. [Text word])," "(Medicine, Chinese Traditional [MeSH Terms] OR Medicine, Chinese Traditional [Text Word] OR Medicine, Chinese Traditional [Text word] OR Tongue Diagnosis, Traditional [Text word] OR Traditional Tongue Assessment [Text word]," "Drugs, Chinese Herbal [MeSH Terms] OR Chinese Drugs, Plant [Text Word] OR Chinese Herbal Drugs [Text word] OR Plant Extracts, Chinese [Text word] OR Chinese Plant Extracts [Text word]," "mechanism," "Meta-analysis," "systematic review," "RCT," "botanical drug" and their combinations were the keywords to search the relevant literature. Data were collected from 2019 to 2025.

mRNA-based COVID-19 vaccines have been associated with rare renal complications, including podocytopathies. We report a 72-year-old Japanese man with a 32-year history of type 2 diabetes and an 11-year history of stable membranous nephropathy (MN) who developed nephrotic syndrome (NS) after receiving his third dose of the BNT162b2 mRNA vaccine. His proteinuria, which had been stable at approximately 0.5 g/gCr for years, acutely increased to 14.3 g/gCr. A kidney biopsy revealed diffuse thickening of the glomerular basement membrane with subepithelial spike formation, and phospholipid A2 receptor (PLA2R)-positive deposits embedded in the membrane (Churg stage 2-4), consistent with his chronic, inactive MN. However, several clinical features were atypical for an MN relapse: serum anti-PLA2R antibodies were undetectable, the protein selectivity index was low (indicating highly selective proteinuria), and a transient spontaneous reduction in proteinuria occurred during hospitalisation. Although early-stage gastric cancer was concurrently detected and curatively resected via endoscopic submucosal dissection, NS recurred shortly thereafter. Proteinuria rapidly decreased to baseline levels following steroid pulse therapy-a therapeutic response characteristic of minimal change disease (MCD). Based on these findings, we diagnosed the patient with vaccine-associated MCD superimposed on stable MN. This case suggests that when an existing glomerular disease follows an unusually acute course after vaccination, clinicians should consider the possibility of a superimposed podocytopathy. Accurate differentiation is essential, as the management of MCD differs significantly from that of MN.

The detection of serum anti-phospholipase A2 receptor (PLA2R) antibodies (SAbs), a method to diagnose membranous nephropathy (MN) that replaces renal biopsy, is becoming increasingly accepted. However, whether SAb detection provides the same clinical value as renal biopsy is uncertain.

The incidence of membranous nephropathy (MN) is gradually increasing; however, safe and effective targeted therapies are still lacking. Ferroptosis may be involved in the disease progression of MN; however, the specific pathways involved remain unknown. This study investigated whether the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway mediates MN progression via ferroptosis. A passive Heymann nephritis rat model was established by tail vein injection of anti-Fx1A. The rats were treated with ferrostatin-1 (Fer-1), the ferroptosis inhibitor, and the Nrf2 inhibitor ML385 for 2 weeks. After treatment, 24-h urine protein samples were collected along with blood and renal tissue samples. Renal tissue pathological damage, lipid peroxidation, iron deposition, ferroptosis-related proteins, and expression of the Nrf2/HO-1 pathway were assessed. The passive Heymann nephritis rat model exhibited massive proteinuria, hypoalbuminemia, and hyperlipidemia. Fer-1 reduced proteinuria, alleviated pathological damage to renal tissues, inhibited lipid peroxidation and iron deposition, suppressed ferroptosis in renal tissues, and restored the expression of Nrf2 and HO-1. Furthermore, when the Nrf2 inhibitor ML385 was combined with Fer-1, the inhibition of Nrf2 exacerbated proteinuria, worsened renal tissue pathological damage, increased lipid peroxidation and iron deposition, and aggravated ferroptosis. These findings demonstrated that ferroptosis inhibition alleviates renal injury in MN by activating the Nrf2/HO-1 pathway, suggesting a potential therapeutic target for this disease.

Acute kidney injury (AKI) occurs in the patients undergoing anti-programmed cell death protein 1-ligand 1 (PD-L1) therapy, indicating that PD-L1 may play a critical role in maintaining renal homeostasis. However, the precise role and mechanism of PD-L1 in AKI remains largely elusive. In this study, we found that PD-L1 was primarily expressed in proximal tubules and significantly upregulated in both murine models of AKI and renal biopsy samples from AKI patients. Genetic specific deletion of PD-L1 in mouse tubular epithelial cells (TECs) exacerbated renal injury in ischemia-reperfusion injury-induced AKI. Mechanistically, PD-L1 was found to interact with BRCA1 and increase BRCA1 expression to safeguard TECs against DNA damage, thereby promoting cellular proliferation and suppressing apoptosis. To translate these findings into a potential therapeutic strategy, we developed a CGA-functionalized extracellular vesicle delivery system for targeted delivery of PD-L1 to injured TECs. This system efficiently restored PD-L1 expression and alleviated DNA damage of TECs in both TEC-specific PD-L1 knockdown and T-cell knockout AKI mouse models. Collectively, these findings uncover a novel function of PD-L1 in promoting adaptive TEC repair through BRCA1 interaction, independent of its canonical immunomodulatory function of T cells, and suggest that PD-L1 supplementation may represent a promising therapeutic strategy for AKI.