Exostosin-2 (EXT2)-associated membranous nephropathy (MN) represents a subgroup of immune complex-mediated renal diseases, where transplantation may facilitate clearance of immune deposits. We present a successful kidney transplantation from a 19-year-old deceased donor with previously undiagnosed EXT2-associated MN into a 75-year-old male recipient. Despite significant pretransplant donor proteinuria (> 300 mg/dL) and hypoalbuminemia, renal biopsies at procurement demonstrated well-preserved renal architecture with minimal interstitial fibrosis. Clinical follow-up showed improvement in recipient renal function, with serum creatinine decreasing from 3.56 mg/dL preoperatively to 0.96 mg/dL (reference range: 0.7-1.3 mg/dL) within 2 months posttransplant. Proteinuria, initially nephrotic-range, progressively resolved to subnephrotic by 4 months. At 6 months, the recipient had normalized renal function and sustained resolution of proteinuria. This case demonstrates that removing a kidney from its native pro-inflammatory environment, coupled with immunosuppression, can facilitate resolution of immune complex-mediated glomerulopathy.

We report a rare case of synchronous stage IV mantle cell lymphoma (MCL) and paraneoplastic membranous nephropathy (MN) in a 48-year-old man. The patient presented with a nasopharyngeal mass; biopsy confirmed cyclin D1-positive MCL harboring the CCND1::IGH rearrangement, along with nephrotic syndrome. Kidney biopsy revealed MN with IgG1/IgG3-dominant glomerular deposits but was negative for PLA2R, THSD7A, and NELL-1 antigens in both renal and tumor tissues, with corresponding serum antibodies undetectable. After lymphoma-directed therapy alone (R-CHOP/R-DHAP induction, autologous hematopoietic stem cell transplantation consolidation, and extended rituximab maintenance), both conditions achieved sustained remission. Complete remission was confirmed per the Lugano 2014 criteria, and nephrotic syndrome resolved, with proteinuria decreasing from 7.38 to 0.29 g/24 hours and serum albumin improving from 26.2 to 35.5 g/L with preserved kidney function. Both MCL and MN remained in remission for >2 years. This case highlights MCL-associated MN as a PLA2R/THSD7A/NELL-1 triple-negative entity where antineoplastic therapy alone induces renal remission, demonstrating both the paraneoplastic mechanism and the feasibility of intensive lymphoma treatment, including transplantation without renal compromise.

Immune-mediated glomerulonephritis represents a diverse group of kidney disorders caused by dysregulated immune responses and constitutes a major contributor to chronic kidney disease. Its pathogenesis can be conceptualized as a three-step cascade: aberrant activation of innate immunity through pattern-recognition receptors, inflammasome complexes, and complement pathways; adaptive immune dysregulation characterized by imbalanced B- and T-cell responses and the production of pathogenic autoantibodies; and terminal effector injury involving complement-mediated damage and progressive fibrosis. This narrative review summarizes current advances in anti-inflammatory biologics that intervene at these critical points across a broad spectrum of entities, including IgA nephropathy (IgAN), membranous nephropathy (MN), lupus nephritis (LN), focal segmental glomerulosclerosis (FSGS), minimal change nephropathy (MCN), anti-glomerular basement membrane (anti-GBM) disease, ANCA-associated vasculitis (AAV), and C3 glomerulopathy (C3G). Therapies including cytokine inhibitors targeting TNF-α or IL-6, B-cell-depleting antibodies such as anti-CD20, plasma cell-directed agents, and complement blockers against C5 or Factor B have demonstrated clinical benefits in IgAN, MN, and LN, where evidence from randomized controlled trials supports their efficacy in reducing proteinuria and preserving renal function. For other entities such as FSGS, MCN, anti-GBM disease, and C3G, the evidence remains preliminary, based largely on case reports, preclinical models, or early-phase trials. Despite therapeutic advances, challenges persist regarding efficacy variability, infection risks, and financial burden. Future research aims to achieve precision therapy through multi-omics-based stratification, next-generation biologics such as bispecific antibodies and gene therapies, and optimized drug delivery systems, steering immune-mediated glomerulonephritis management toward truly disease-modifying treatment.

Chimeric antigen receptor (CAR) T-cell therapy is a new type of highly precise and targeted immunotherapy for urological diseases. It has demonstrated significant therapeutic potential in chronic and autoimmune kidney diseases such as renal fibrosis and membranous nephropathy. However, owing to its high cost, low efficiency, and serious side effects, such as cytokine storm syndrome, a new generation of drugs has emerged to solve these problems. In vivo CAR T-cell therapy is a treatment method that directly modifies specific cells within the patient's body through various delivery systems. Nonviral vectors (nanoparticles and exosomes) and viral vectors (adeno-associated viruses and lentiviruses) can be engineered to achieve better therapeutic effects. By taking advantage of different delivery systems and minimizing their drawbacks, in vivo CAR T-cell therapy can improve the stability and targeting ability, reduce immunogenicity, and minimize side effects. This review summarizes the mechanisms of action and clinical applications of various delivery systems used in in vivo CAR T-cell therapy, highlighting their potential in the treatment of urological diseases. Through a deeper understanding of the construction and optimization of well-designed platforms, the development of optimal delivery systems has valuable implications for the establishment of new pharmaceuticals for in vivo CAR T-cell therapy in urological diseases.

With the expanding identification of target antigens in primary membranous nephropathy (PMN), treatment is shifting from empirical immunosuppression toward mechanism-based precision immunotherapy. Although rituximab (RTX) has substantially improved the management of PMN, a considerable proportion of patients still experience suboptimal response, relapse, or resistance. Accumulating evidence indicates that RTX resistance is a multifactorial process involving anti-drug antibody formation, reduced bioavailability, incomplete depletion of pathogenic B cells within lymphoid compartments, CD20 internalization and degradation, epitope spreading, persistence of autoantibodies against intracellular antigens, and genetic susceptibility. In response, a broad range of mechanism-guided therapeutic strategies is emerging, including next-generation anti-CD20 monoclonal antibodies, agents targeting distinct stages of B-cell differentiation, and advanced immune-engineering approaches such as CAR-T, CAAR-T, CAAR-NK, CAR-Treg, CAR-macrophage therapies, sweeping antibodies, antibody-drug conjugates, and bispecific autoantigen-T-cell engagers. In parallel, interventions targeting aberrant T-B cell crosstalk and complement activation are providing additional therapeutic opportunities for refractory disease. This review systematically summarizes the major pathogenic mechanisms underlying RTX-resistant PMN and integrates the latest advances in mechanism-based therapeutic strategies, with the aim of informing individualized treatment approaches and future translational research for refractory PMN.

Huaier Granules, an aqueous extract preparation of Trametes robiniophila Murr, has been verified effective in treating various malignant tumors. Many agents used for membranous nephropathy, including cyclophosphamide and rituximab (RTX), were initially developed for cancer therapy. However, no previous studies have explored its application in adult idiopathic membranous nephropathy (IMN). This case series analyzed clinical data of 2 high-risk IMN patients admitted to our hospital from 2023 to 2026. All patients were confirmed by renal biopsy and anti-phospholipase A2 receptor (anti-PLA2R) antibody testing. They received combined therapy of Huaier Granules plus renin-angiotensin system inhibitors (RASi) as the basic treatment. After over 12 months of treatment, laboratory results showed negative anti-PLA2R antibody levels; 24-hour urinary protein, serum albumin and estimated glomerular filtration rate (eGFR) were improved compared with baseline. Case 1 was followed up for 25 months and Case 2 was followed up for 21 months. Case 1 achieved complete clinical remission and Case 2 partial remission. No obvious adverse reactions related to Huaier Granules were observed, with good patient tolerance. This regimen may provide a new adjuvant therapeutic strategy for clinical management of IMN.

Idiopathic membranous nephropathy (IMN) is one of the main causes of adult nephrotic syndrome. A subset of untreated or inadequately treated patients eventually progress to end-stage renal disease (ESRD), posing a significant clinical challenge. Although the discovery of novel podocyte target antigens has deepened our understanding of IMN pathogenesis, the precise molecular mechanisms remain incompletely elucidated, and effective targeted therapies are still lacking. Animal models play an irreplaceable role in uncovering IMN pathogenesis and developing effective therapies. In recent years, with a deeper understanding of IMN, researchers have successfully established various animal models, including Heymann nephritis (HN), cationic bovine serum albumin (C-BSA), Aminopeptidase A (APA), thrombospondin type 1 domain-containing 7A (THSD7A)-related, and phospholipase A2 receptor (PLA2R)-related IMN models. These models have substantially advanced the simulation of pathological human IMN features. Notably, the development of human PLA2R1-related animal models marks a landmark breakthrough in this field, as these models are the first to recapitulate the immunopathological processes driven by a key human autoantigen in experimental animals. However, current animal models have their own limitations and still cannot fully replicate the complex pathological process of human IMN. This review summarizes recent progress in animal IMN models, analyzes their methods, pathological features, strengths, and limitations, and discusses future directions. Future model development should integrate advanced multi-omics and artificial intelligence (AI) to achieve greater accessibility and precision, enabling the construction of multidimensional models encompassing genetics, environment, and immunity, thereby enabling a leap from "disease simulation" to "personalized treatment".

Detection of anti-phospholipase A2 receptor (PLA2R) antibody levels is a non-invasive method for the diagnosis of primary membranous nephropathy (PMN). However, diagnosing PMN becomes challenging when anti-PLA2R antibody levels are less than 20 RU/ml. Therefore, this investigation aimed to assess the diagnostic efficacy of time-resolved fluorescence immunoassay (TRFIA) for the detection of anti-PLA2R antibodies. A total of 201 patients with anti-PLA2R antibody levels between 2 and 20 RU/ml were included. Baseline serum samples were tested via ELISA and both direct and indirect TRFIA. Renal biopsy results indicated that 56% patients were diagnosed as PMN. The direct and indirect TRFIA demonstrated significant improvement in sensitivity and specificity for the detection of anti-PLA2R-IgG/IgG4. Indirect TRFIA showed the best sensitivity and specificity for the detection of anti-PLA2R-IgG4, with an optimal cutoff value of 65.34 ng/ml (sensitivity/specificity: 83.9%/94.4%). Logistic regression analysis indicated that anti-PLA2R-IgG4 detected via indirect TRFIA serves as an independent diagnostic marker for PMN patients with low antibody titers (OR = 62.097, P < 0.001). In conclusion, both direct and indirect TRFIA exhibit significant advantages in the diagnosis of PMN, particularly with anti-PLA2R-IgG4 detected by indirect TRFIA. These methods facilitate more accurate diagnosis of PMN and reduce reliance on invasive renal biopsies.