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Membranous nephropathy

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Membranous nephropathy. Core disease mechanisms, molecular and cellular pa...

2026-04-14
Asta MONDO:0005376 Model: Asta Scientific Corpus Retrieval 17 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Membranous nephropathy. Core disease mechanisms, molecular and cellular pa...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 17
  • Snippets retrieved: 20

Relevant Papers

[1] Unraveling Primary Membranous Nephropathy Using Proteogenomic Studies

  • Authors: Omar Ragy, P. Hamilton, D. Kanigicherla
  • Year: 2021
  • Venue: Urinary Tract Infection and Nephropathy - Insights into Potential Relationship [Working Title]
  • URL: https://www.semanticscholar.org/paper/a3540dbb14ce21aa09f82627cc931ddfa6ffa444
  • DOI: 10.5772/intechopen.97622
  • Summary: This chapter focuses on the links identified between primary membranous nephropathy and underlying gene polymorphism, and pathways using both proteomics and transcriptomic analysis.
  • Evidence snippets:
  • Snippet 1 (score: 0.631) > Management of membranous nephropathy remains a continuing challenge in the field of nephrology. Over the last 50 years, we have been classifying and managing membranous nephropathy based on both histological and clinical phenotyping, which is the key feature guiding treatment decisions. However, in recent years other mechanisms have come to shed light on the heterogeneity of membranous nephropathy and clinical outcomes. With the emergence of proteogenomic analysis, the classification of other nephrotic syndromes has advanced immensely [1]. Therefore, the potential value for membranous nephropathy is to be considered. > Varied clinical manifestation may be due to the polymorphic gene expression in the immune system as well as at the glomerular filtration barrier site, which comprises podocytes, endothelial cells, and intervening glomerular basement membrane [2]. In addition to the multiple immune cascade pathways, underlying complex molecular and cellular processes are identified by proteomics and transcriptomics in glomerular disorders like Minimal Change Disease and focal segmental glomerulosclerosis (FSGS) [1]. Early data suggest that gene expression and molecular pathways are both potential emerging therapeutic targets in the era of precision medicine in these disorders. > Primary membranous nephropathy is considered an autoimmune disease, associated with autoantibodies recognizing a target antigen on the podocytes. The connection between the immune system and underlying cellular pathways in the pathophysiology of membranous nephropathy has been an area of extensive research. Even though membranous nephropathy does not follow the mendelian trait, the role of underlying genetic factors was examined in previous studies. > Although clinical and histological apparency of membranous nephropathy are seemingly similar, response to immunosuppressive therapy can be variable with poor response to treatment in some patients whilst about a third of the patients have minimal to no long-term consequence following spontaneous remission.

[2] Network analysis of membranous glomerulonephritis based on metabolomics data

  • Authors: Amir Taherkhani, S. Kalantari, Afsaneh Arefi Oskouie, M. Nafar, M. Taghizadeh et al.
  • Year: 2018
  • Venue: Molecular Medicine Reports
  • URL: https://www.semanticscholar.org/paper/7722ec312f589729d9818ddc9adf2c42a39b383b
  • DOI: 10.3892/mmr.2018.9477
  • PMID: 30221719
  • PMCID: 6172390
  • Citations: 21
  • Summary: The present study aimed to identify diagnostic metabolites that are involved in the development of the disease using topological features in the component-reaction-enzyme-gene (CREG) network for MGN using molecular complex detection and ClueGene Ontology.
  • Evidence snippets:
  • Snippet 1 (score: 0.544) > Membranous glomerulonephritis (MGN) is the most common cause of nephrotic syndrome in adults >60 years old (1,2). Rivera et al (3) suggested that MGN was the pathology in 15.9-32.9% of all nephrotic syndrome cases. Of all cases, 75% are classified as primary or idiopathic MGN; secondary MGN is associated with various conditions, including hepatitis infection, malignancy, systematic lupus erythematosus and drug intoxication (4,5). MGN is histopathologically characterized by the thickening of the glomerular basement membrane (GBM) and the subepithelial deposition of immune complexes (5). Electron microscopy has demonstrated that subepithelial/intramembranous immune deposits (immunoglobulin G and complement) cause podocyte damage, which is usually associated with nephrotic syndrome (4). A deterioration in renal function and the development of end-stage renal disease occur in ~40% of patients with primary MGN (5). Proteinuria (6,7), edema (8,9), hyperlipidemia (10,11) and hypoalbuminemia (12,13) are non-specific clinical symptoms of MGN. However, renal biopsy is the only definitive diagnostic approach, although it is an invasive procedure. Despite research in this field, the exact mechanisms of the development and progression of the disease have not been fully elucidated (14). > Systems biology gives meaning to large amounts of data derived from '-omics-' technologies (15). The '-omics-' technologies refer to high-throughput techniques, which may simultaneously detect a large number of molecules (including genes, transcriptomes, proteins and metabolites) in complex bio-samples (16). This approach may reduce the restrictions in the field of diagnosis and contribute to the understanding of the mechanisms involved in the pathogenesis of disease. > Metabolites are downstream products of gene expression and protein activity; therefore, they may provide an immediate indication of the biological phenotype (17).

[3] Membranous nephropathy as a rare renal manifestation of IgG4-related disease

  • Authors: AA Kurien, A. Raychaudhury, P. Walker
  • Year: 2015
  • Venue: Indian Journal of Nephrology
  • URL: https://www.semanticscholar.org/paper/f5bbbb54f2c78e995da4cf15a275ff623ff2a763
  • DOI: 10.4103/0971-4065.143300
  • PMID: 26060366
  • PMCID: 4446921
  • Citations: 6
  • Summary: A patient with IgG4 renal disease who had membranous nephropathy as well as TIN is reported, indicating a newly described immune-mediated disorder with tissue infiltration of IgG 4-positive plasma cells.
  • Evidence snippets:
  • Snippet 1 (score: 0.537) > Membranous nephropathy may be primary or secondary to a variety of causes. One of the major causes of primary membranous nephropathy is the development of antibodies against a podocyte antigen, M-type PLA2R. [5] utoimmune disease, infections, neoplasms and drugs are the main etiologic factors of secondary membranous nephropathy. Recently, a series of published literature suggested that IgG4-RD is another systemic disease, which is an etiological factor for secondary membranous nephropathy. [6] In 2011, the international symposium on IgG4-RD in the nomenclature consensus statement termed membranous nephropathy secondary to IgG4-RD as "IgG4-related membranous nephropathy". [7] Anti-PLA2R antibody staining is a useful marker for differentiating primary from secondary membranous nephropathy in adults. [8] Anti-PLA2R antibody staining was negative in this patient, as is expected in a case of secondary membranous nephropathy. Work up on our patient did not reveal any evidence of underlying autoimmune disease, infection or malignancy. No drug history was elicited. Considering a background of secondary membranous nephropathy, we attribute it to IgG4-RD because the following diagnostic criteria were fulfilled. [9] Clinical criteria of nephrotic syndrome with renal dysfunction • High serum IgG4 level and high IgG4/IgG ratio • Histological picture of membranous nephropathy confirmed by electron microscopy study along with interstitial fibrosis and dense infiltration of IgG4 positive plasma cells. > The etiopathogenesis of membranous nephropathy developing in the setting of IgG4-RD is unclear. > A hypothesis put forward by Fervenza et al. is that the proliferating plasma cells produce IgG4 that is autoreactive against podocyte antigens. [10]

[4] Membranous Nephropathy: Current Understanding in The Light of New Advances

  • Authors: H. Ozer, I. Baloglu, F. Fervenza, K. Turkmen
  • Year: 2023
  • Venue: Turkish Journal of Nephrology
  • URL: https://www.semanticscholar.org/paper/0ce05309e95ca7a35558cb30763ea134592caee3
  • DOI: 10.5152/turkjnephrol.2023.22123421
  • Citations: 1
  • Summary: Treatment in membranous nephropathy has turned to more specific therapies that are more selective in targeting antibody-producing cells, such as rituximab.
  • Evidence snippets:
  • Snippet 1 (score: 0.536) > Membranous nephropathy (MN) is a non-inflammatory autoimmune disease defined by the presence of subepithelial immune deposits localized between the podocyte and the glomerular basement membrane (GBM) on electron microscopy examination. Although terms such as membranous glomerulonephritis or epimembranous glomerulonephritis were used to name the disease in the past, the term membranous nephropathy is often preferred today, especially because of its noninflammatory character. It is the most common cause of primary nephrotic syndrome (NS) in adults, with an annual incidence of 1/100 000 cases. It is most often detected in the 40s and is more common in men than in women. 1,2 About 70%-80% of MN patients are classified as primary MN, while 20%-30% are classified as secondary MN. 3 The most common underlying causes of secondary MN are infections, drugs, malignancies, and autoimmune diseases. The frequency of secondary MN is higher in patients diagnosed with MN in childhood or advanced ages, and detailed research should be done on the underlying causes. factors trigger a loss of tolerance for an autoantigen, resulting in B cell activation and autoantibody production. These autoantibodies damage the podocytes through complement-related and complement-independent mechanisms, resulting in the development of proteinuria. 4,5 rly processes in elucidating the pathogenesis were presented with the Heymann nephritis model in the mouse. It has been shown that immune deposits accumulate in the subepithelial part of the GBM as a result of the binding of circulating immunocomplexes to antigens on the glomerular capillary membrane. Immune complex formations cause local activation of the complement system and result in complement-related cellular damage, GBM, and podocyte damage. 6 The injury process is chronic and ultimately results in severe proteinuria, which is the typical clinical manifestation of MN patients. > However, the podocyte protein targeted in the Heymann nephritis model is megalin, which has been identified in mice but is not expressed in humans.

[5] Identification Exploring the Mechanism and Clinical Validation of Mitochondrial Dynamics-Related Genes in Membranous Nephropathy Based on Mendelian Randomization Study and Bioinformatics Analysis

  • Authors: Qiuyuan Shao, Nan Li, Huimin Qiu, Min Zhao, Chunming Jiang et al.
  • Year: 2025
  • Venue: Biomedicines
  • URL: https://www.semanticscholar.org/paper/dae27fc292080b60dbd3afb20a41bc95678b8048
  • DOI: 10.3390/biomedicines13061489
  • PMID: 40564208
  • PMCID: 12191289
  • Summary: These findings elucidate the molecular underpinnings of MDG-mediated mechanisms in MN, revealing novel diagnostic biomarkers and therapeutic targets and underscore the interplay between mitochondrial dynamics and immune dysregulation in MN progression, providing a foundation for precision medicine strategies.
  • Evidence snippets:
  • Snippet 1 (score: 0.514) > Membranous nephropathy (MN) is a prominent glomerular pathology characterized by the deposition of subepithelial immune complexes along the glomerular basement membrane, leading to the clinical manifestation of nephrotic syndrome [1]. Epidemiological studies indicate that the global incidence of membranous nephropathy (MN) is approximately 8-10 cases per million population. The incidence is marginally higher in the United States, reaching 12 cases per million population [2]. In China, MN accounts for over 20% of primary glomerular diseases, with primary MN constituting approximately 80% of all MN cases [2,3]. Among White adults, MN represents the most common etiology of primary nephrotic syndrome [3]. The clinical trajectory of MN exhibits considerable heterogeneity: while spontaneous remission occurs in roughly one-third of cases, another third maintain stable renal function despite persistent proteinuria. The remaining third face a substantial risk of progression to end-stage renal disease in the absence of timely diagnosis and intervention. Existing therapeutic regimens-centered on immunosuppressive therapy and supportive management-often fail to prevent relapse, highlighting a critical need for novel and more effective treatment strategies [4,5]. Elucidating the molecular mechanisms underlying MN is therefore imperative for the discovery of reliable diagnostic biomarkers and the development of targeted therapeutic interventions to improve clinical outcomes. > Mitochondrial dynamics (MD), encompassing mitochondrial fusion, fission, and turnover processes, are essential for maintaining organellar integrity and bioenergetic function. These dynamic processes are integral to ATP generation and exert regulatory influence over key cellular activities, including apoptosis and intracellular signaling pathways [6,7]. Disruptions in MD have been implicated in the pathophysiology of MN, where impaired mitochondrial function may amplify oxidative stress and inflammatory responses, thereby exacerbating renal injury [8,9].
  • Snippet 2 (score: 0.474) > Membranous nephropathy (MN) constitutes a leading etiology of adult-onset nephrotic syndrome, where current therapeutic approaches, including immunosuppressive regimens, frequently fail to address either the underlying molecular pathogenesis or the persistent risk of disease recurrence [45]. Notably, dysregulation of mitochondrial dynamics (MD) disrupts cellular bioenergetic homeostasis, driving aberrant cellular fate determination through compromised mitochondrial quality control. In the renal tubular compartment, MD abnormalities may induce tubular epithelial atrophy, inflammatory cascades, and programmed cell death-pathobiological processes that collectively propagate renal disease progression [46]. Nevertheless, the precise mechanistic involvement of MD in MN pathogenesis remains incompletely characterized. To elucidate the molecular mechanisms underpinning MN, this study investigated the involvement of MD in disease pathogenesis. Transcriptomic datasets from public repositories were integrated with MR and machine-learning methodologies to identify MD-associated genes implicated in MN. Four candidate genes-MYO9A, NFKBIZ, RTTN, and USP40-were suggested to be involved in the pathological process of MN. Additionally, scRNA-seq analysis identified mesenchymal-epithelial transitioning cells as pivotal in the disease microenvironment. This comprehensive molecular characterization advances our current understanding of MN pathophysiology and lays a foundation for the development of targeted therapeutic interventions aimed at improving clinical outcomes. > Myosin IXA (MYO9A), a member of the myosin superfamily ubiquitously expressed in eukaryotic cells, exhibits low-level constitutive expression in renal tubular epithelial cells (particularly within proximal tubules and collecting ducts), while demonstrating significantly higher expression in renal interstitial fibroblasts [46]. This motor protein primarily modulates intracellular cytoskeletal architecture and dynamic remodeling, facilitating cellular migration and proliferative responses that contribute to progressive renal fibrogenesis [47].

[6] Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy

  • Authors: Hua Miao, Ya-mei Zhang, Xiaoyong Yu, Liang Zou, Ying-yong Zhao
  • Year: 2022
  • Venue: Frontiers in Pharmacology
  • URL: https://www.semanticscholar.org/paper/3fa43ea5478f6dc7da789c08449dd33e7900f1c6
  • DOI: 10.3389/fphar.2022.969930
  • PMID: 36176440
  • PMCID: 9513429
  • Citations: 43
  • Influential citations: 2
  • Summary: The identification of nephritogenic autoantibodies against neutral endopeptidase, phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) antigens provide more specific concept-driven intervention strategies for treatments by specific B cell-targeting monoclonal antibodies to inhibit antibody production and antibody-antigen immune complex deposition.
  • Evidence snippets:
  • Snippet 1 (score: 0.498) > Membranous nephropathy (MN) is a major cause of antibody-associated nephrotic syndrome among adults (Gianassi et al., 2019;Ronco et al., 2021). The development of disease is triggered by accumulation of immune complex deposition in the subepithelial region with local complement activation and injury to podocytes and glomerular basement membrane (GBM) thickening (Feng et al., 2020). While 70%-80% of MN is classified as idiopathic or primary MN, the rest of MN is triggered by secondary causes, such as infections, malignancies or autoimmune diseases (Ronco et al., 2021). The two distinct types require different management approaches. In primary MN, approximately 30% of patients can improve by spontaneous remission, while the remainder show persistent proteinuria or progression to end-stage renal disease (Ronco et al., 2021). In the most severe cases, immunosuppressant treatment is required. Secondary MN requires treatment of the underlying diseases. In most patients, MN is an autoimmune disease mediated by autoantibodies directed against phospholipase A 2 receptor (PLA 2 R) or, more unusually, thrombospondin type-1 domaincontaining 7A (THSD7A) (Deng et al., 2021). However, THSD7A is not specific for primary MN. When secondary causes are excluded, the disease is called primary MN. To date, the diagnosis of MN can only be determined by renal biopsy. In recent years, MN pathogenesis was investigated by using both patients and animal models to help understand the underlying molecular mechanisms for development of immune complex deposition in GBM (Sinico et al., 2016). > This review considers the underlying molecular pathomechanisms of MN, with a particularly focus on novel pathomechanisms such as dysbiosis of gut microbiota, dysregulation of Non-coding RNAs (long non-coding RNAs, microRNAs), aberrant expression of identified proteins by using proteomics and the disorder of endogenous metabolites by metabolomics, as well as altered DNA methylation.

[7] Analysis of gene expression and use of connectivity mapping to identify drugs for treatment of human glomerulopathies

  • Authors: Chen-Fang Chung, J. Papillon, José R. Navarro-Betancourt, Julie Guillemette, Ameya Bhope et al.
  • Year: 2023
  • Venue: Frontiers in Medicine
  • URL: https://www.semanticscholar.org/paper/7b53c0748f67b7956b93e7db636b343c4d2c520d
  • DOI: 10.3389/fmed.2023.1122328
  • PMID: 36993805
  • PMCID: 10042326
  • Citations: 8
  • Summary: The possibility for modulating the UPR or autophagy pharmacologically as therapy for GN is opened, and one of these drugs attenuated injury of glomerular cells is shown to be cytoprotective.
  • Evidence snippets:
  • Snippet 1 (score: 0.480) > Human glomerular diseases, including primary glomerulonephritis (GN)-membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN), as well as diabetic nephropathy (DN) are leading causes of chronic kidney disease, and have a major impact on health (1). Current therapies of GN and DN are only partially effective, significantly toxic and lack specificity. Thus, mechanism-based therapies are desirable. > Glomerular visceral epithelial cells (GECs, podocytes), mesangial and endothelial cells may all be involved in the pathogenesis of GN and DN. Among these cells, podocytes are vital in maintaining glomerular capillary wall permselectivity (2,3) and podocyte injury is believed to be key to the pathogenesis of GN and DN. Injury may be initiated by autoantibodies to glomerular components or circulating immune complexes that deposit in glomeruli and lead to the activation of complement (MN and IgAN) (4). Alternatively, a circulating factor toxic to podocytes induces injury (FSGS) (5). In DN, hyperglycemia and oxidative stress lead to podocyte and mesangial injury (6). These distinct stimuli may activate or disturb various metabolic pathways in glomerular cells; e.g. in podocytes this results in disruption of the cytoskeleton, membrane composition and structure, adhesion to the glomerular basement membrane, or the function of organelles (due to ATP depletion). Conversely, other pathways may be activated in parallel in the glomerulus to attenuate cell injury or promote repair. These pathways may include protein kinases, cytokines, endoplasmic reticulum (ER) stress/unfolded protein response (UPR), ubiquitinproteasome system and autophagy (7).

[8] Targeting necroptosis in fibrosis

  • Authors: Emad H. M. Hassanein, Islam M. Ibrahim, Mostafa S Abd El-Maksoud, Mostafa K Abd El-Aziz, Esraa K. Abd-alhameed et al.
  • Year: 2023
  • Venue: Molecular Biology Reports
  • URL: https://www.semanticscholar.org/paper/d1916874c90b07113252310014a74ec21f0f6020
  • DOI: 10.1007/s11033-023-08857-9
  • PMID: 37910384
  • PMCID: 10676318
  • Citations: 7
  • Summary: This review helps to clarify the role of necroptosis in fibrosis and will encourage clinical efforts to target this pathway of programmed cell death.
  • Evidence snippets:
  • Snippet 1 (score: 0.478) > Chronic kidney disease (CKD) is a significant epidemiological clinical problem with a high prevalence Fig. 1 The main mechanism of fibrosis and mortality rate. End-stage renal disease can be developed from CKD and result in serious complications [27]. Diabetic nephropathy, hypertension, and chronic interstitial glomerulonephritis are the most common causes of CKD. These diseases can cause structural and functional changes in the kidney. Chronic inflammation can cause renal fibrosis and is a major predisposing factor in CKD [28]. In addition, various cells, like macrophages, participate in renal fibrosis [29][30][31]. Renal fibrosis frequently leads to renal interstitial fibrosis with tubular atrophy and abnormal ECM deposition as the main pathological causes [32]. Renal fibrosis characterized by inflammatory cell infiltration, fibroblast activation, ECM component deposition, and microvascular thinning [33]. Many molecules and cells, such as angiotensin II (Ang II), are linked to the progression of renal fibrosis [34]. Animal models such as surgical, chemical, physical, genetic, and in vitro models are essential for understanding renal fibrosis biopathology and evaluating new therapies [35]. However, there are no available drugs for renal fibrosis. As a result, improving our understanding of renal fibrosis's cellular and molecular mechanisms is critical to eliminating renal fibrosis [36]. Alleviation of fibrosis alone is not sufficient to repair kidney function without restoring lost nephron tissue after damage. It is worth noting that encouraging endogenous tissue regeneration could be a promising treatment option for kidney disease [37].

[9] Chronic kidney disease enhances alternative pathway activity: a new paradigm

  • Authors: Diana I. Jalal, Joshua M. Thurman, Richard J. H. Smith
  • Year: 2025
  • Venue: The Journal of Clinical Investigation
  • URL: https://www.semanticscholar.org/paper/edd1c33a4f3bdefe1d963d95d22ca44188abaa1c
  • DOI: 10.1172/JCI188353
  • PMID: 40309771
  • PMCID: 12043098
  • Citations: 3
  • Summary: The need for ongoing research efforts that may lead to opportunities to target the alternative pathway of complement with the goal of improving kidney and cardiovascular outcomes in persons with reduced kidney function is highlighted.
  • Evidence snippets:
  • Snippet 1 (score: 0.478) > Alternative pathway activation contributes to several kidney diseases (51). In some diseases (e.g., C3 glomerulopathy [C3G] and complement-mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome [aHUS]), uncontrolled complement activation is the primary driver of kidney injury (52). In other kidney diseases, secondary activation of the alternative pathway occurs and contributes to disease progression. For example, there is strong preclinical and clinical evidence for a role of the alternative pathway in immune-complex membranoproliferative glomerulonephritis (53), lupus nephritis (54,55), membranous nephropathy (56), IgA nephropathy (57), antineutrophil cytoplasmic antibody associated vasculitis (58), and acute tubular injury (59,60). Although the underlying mechanisms of complement activation vary across these conditions, shared involvement of the complement system suggests that there are anatomic or physiologic features of the kidney that render it particularly susceptible to alternative pathway-mediated injury. > Many of the mechanisms of complement dysregulation first identified in C3G and aHUS have subsequently been observed in the other, more prevalent, kidney diseases. A good example is autoantibodies against factor H (FHAA), which were first appreciated as a cause of aHUS but have recently been detected in patients with C3G, recurrent membranous nephropathy, and monoclonal gammopathy of renal significance (61,62). Similarly, the role of factor H-related proteins (FHRs) in complement control has been elucidated by studying C3G and then translated to other diseases. For example, elevated levels of FHR1 and FHR5 have been shown to promote alternative pathway activation and to correlate with faster disease progression in IgA nephropathy (63,64). In diabetic kidney disease, alternative pathway activation and reduced expression of factor H have been reported (65,66) and urinary levels of FHR2 have been shown to predict CKD progression (67).

[10] SPP1 as a biomarker for idiopathic membranous nephropathy progression and its regulatory role in inflammation and fibrosis

  • Authors: Shuting Pang, Rongbin Zhou, Zige Liu, Boji Xie, Fugang Liu et al.
  • Year: 2025
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/41b35d9a14d8bb8d16ff1f49a9c8462c12ba2dbf
  • DOI: 10.3389/fimmu.2025.1671891
  • PMID: 41080598
  • PMCID: 12510867
  • Citations: 2
  • Summary: SPP1 was identified as a promising biomarker for IMN, demonstrating a critical role in promoting fibrosis and inflammatory responses associated with the disease, and its potential as a novel therapeutic target for IMN intervention is suggested.
  • Evidence snippets:
  • Snippet 1 (score: 0.474) > Idiopathic Membranous Nephropathy (IMN) accounts for approximately 30% of adult nephrotic syndrome cases (1), with nearly 40% of patients progressing to end-stage renal disease (2,3). Early detection and timely intervention can significantly improve outcomes while reducing the socioeconomic burden. Pathologically, IMN is characterized by immune complex deposition, complementmediated proteinuria, and progressive renal impairment (4). Current clinical staging relies on histopathological features including the degree of glomerular basement membrane thickening, presence of spike formations, and immunoglobulin deposition patterns (5). These pathological classifications facilitate disease progression monitoring and prognosis prediction. The disease pathogenesis involves inflammatory cell infiltration and subsequent release of vasoactive mediators, leading to vascular hyperpermeability, leukocyte recruitment, and other inflammatory injuries (6). These processes represent critical pathological hallmarks that drive IMN progression to chronic kidney disease. Ultimately, renal fibrosis progression and sustained immune activation form the core pathological mechanisms in IMN development, suggesting that modulation of inflammatory responses may serve as a promising therapeutic strategy. > Genetic alterations are closely associated with disease pathogenesis. Accumulating evidence indicates that differentially expressed genes may serve as both reliable disease biomarkers and promising therapeutic targets (7). In recent years, RNA sequencing (RNA-seq), particularly single-cell RNA sequencing (scRNA-seq), has revolutionized our understanding of cellular heterogeneity and intercellular communication networks owing to its unparalleled capacity for comprehensive and precise gene expression profiling (8). This cutting-edge technology has substantially advanced research in renal pathophysiology, facilitating the identification of diagnostic biomarkers and discovery of novel therapeutic targets. > Urine contains various exfoliated renal cells with significant research value. Studies have demonstrated that urine from both healthy and diseased kidneys contains sufficient exfoliated proximal tubular cells (PTCs) that can reflect renal functional changes (9).

[11] CKD therapy to improve outcomes of immune-mediated glomerular diseases.

  • Authors: Hans-Joachim Anders, G. Fernández-Juárez, A. Vaglio, P. Romagnani, J. Floege
  • Year: 2023
  • Venue: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • URL: https://www.semanticscholar.org/paper/47e9fb8b19765676d2dc40010ab473813eb996a1
  • DOI: 10.1093/ndt/gfad069
  • PMID: 37218706
  • Citations: 16
  • Summary: Non-pharmacological interventions include reducing salt intake, normalizing body weight, avoiding superimposed kidney injuries, smoking cessation, and regular physical activity, and drug interventions to attenuate CKD progression in immune-mediated kidney disorders are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.468) > The management of IgA nephropathy, membranous nephropathy, lupus nephritis, ANCA-associated vasculitis, C3 glomerulonephritis, autoimmune podocytopathies and other immune-mediated glomerular disorders is focused on two major treatment goals, namely preventing overall mortality and the loss of kidney function. As minimizing irreversible kidney damage best serves both goals, the management of immune-mediated kidney disorders must focus on the two central pathomechanisms of kidney function decline, i.e. controlling the underlying immune disease process, e.g. with immunotherapies, and controlling the non-immune mechanisms of chronic kidney disease (CKD) progression. Here we review the pathophysiology of these non-immune mechanisms of CKD progression and discuss non-drug and drug interventions to attenuate CKD progression in immune-mediated kidney disorders. Non-pharmacological interventions include reducing salt intake, normalizing body weight, avoiding superimposed kidney injuries, smoking cessation, and regular physical activity. Approved drug interventions include inhibitors of the renin-angiotensin-aldosterone system and of the sodium-glucose-transporter-2. Numerous additional drugs to improve CKD care are currently being tested in clinical trials. Here we discuss about how and when to use these drugs in the different clinical scenarios of immune-mediated kidney diseases.

[12] Bioinformatics Analysis Reveals a Shared Pathway for Common Forms of Adult Nephrotic Syndrome

  • Authors: Dengfeng Li, Liang Liu, M. Murea, B. Freedman, Lijun Ma
  • Year: 2023
  • Venue: Kidney360
  • URL: https://www.semanticscholar.org/paper/e63be82d34013bce442e57bb003357e86ed12bb6
  • DOI: 10.34067/KID.0000000000000074
  • PMID: 36763793
  • PMCID: 10278839
  • Citations: 3
  • Summary: Key Points Dysregulation of the focal adhesion pathway is present in the three most common forms of glomerular disease, that is, Focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease. Zyxin is seen to be upregulated in the glomerular compartment of patients with the three most common forms of glomerular disease. Background Focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease are common causes of nephrotic syndrome. Although tr...
  • Evidence snippets:
  • Snippet 1 (score: 0.461) > Key Points Dysregulation of the focal adhesion pathway is present in the three most common forms of glomerular disease, that is, Focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease. Zyxin is seen to be upregulated in the glomerular compartment of patients with the three most common forms of glomerular disease. Background Focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease are common causes of nephrotic syndrome. Although triggers for these diseases differ, disease progression may share common molecular mechanisms. The aim of this study was to investigate the presence of molecular pathways that are dysregulated across these glomerular diseases. Methods The gene expression dataset GSE200828 from the Nephrotic Syndrome Study Network study was obtained from the Gene Expression Omnibus database. R and Python packages, Cytoscape software, and online tools (DAVID and STRING) were used to identify core genes and topologically relevant nodes and molecular pathways. Single-cell RNA sequencing analysis was applied to identify the expression patterns of core genes across kidney cell types in glomerular compartments. Results A total of 1087 differentially expressed genes were identified, including 691 upregulated genes and 396 downregulated genes, which are common in all three forms of nephrotic syndrome compared with kidney donor controls (FDR P<0.01). A multiapproach bioinformatics analysis narrowed down to 28 similarly dysregulated genes across the three proteinuric glomerulopathies. The most topologically relevant nodes belonged to the adherens junction, focal adhesion, and cytoskeleton pathways, where zyxin covers all of those gene ontology terms. Conclusions We report that dysregulation of cell adhesion complexes was present in the three most common forms of glomerular disease. Zyxin could be a biomarker in all three common forms of nephrotic syndrome. If further functional studies confirm its role in their development, zyxin could be a potential therapeutic target.

[13] Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment

  • Authors: E. Chung, Yuanmin Wang, Karen Keung, M. Hu, H. McCarthy et al.
  • Year: 2022
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/7b40cada96927dcd51cc90ac2b900cd8de74fa74
  • DOI: 10.3389/fimmu.2022.1036249
  • PMID: 36405681
  • PMCID: 9667740
  • Citations: 21
  • Summary: Current understanding of the immune mechanisms driving PMN from animal models and clinical studies are summarized, and the implications on the development of future targeted therapeutic strategies are summarized.
  • Evidence snippets:
  • Snippet 1 (score: 0.456) > Primary membranous nephropathy (PMN) is one of the common causes of adult-onset nephrotic syndrome and is characterized by autoantibodies against podocyte antigens causing in situ immune complex deposition. Much of our understanding of the disease mechanisms underpinning this kidneylimited autoimmune disease originally came from studies of Heymann nephritis, a rat model of PMN, where autoantibodies against megalin produced a similar disease phenotype though megalin is not implicated in human disease. In PMN, the major target antigen was identified to be M-type phospholipase A2 receptor 1 (PLA2R) in 2009. Further utilization of mass spectrometry on immunoprecipitated glomerular extracts and laser micro dissected glomeruli has allowed the rapid discovery of other antigens (thrombospondin type-1 domain-containing protein 7A, neural epidermal growth factor-like 1 protein, semaphorin 3B, protocadherin 7, high temperature requirement A serine peptidase 1, netrin G1) targeted by autoantibodies in PMN. Despite these major advances in our understanding of the pathophysiology of PMN, treatments remain non-specific, often ineffective, or toxic. In this review, we summarize our current understanding of the immune mechanisms driving PMN from animal models and clinical studies, and the implications on the development of future targeted therapeutic strategies.
  • Snippet 2 (score: 0.456) > Primary membranous nephropathy (PMN) is one of the common causes of adult-onset nephrotic syndrome and is characterized by autoantibodies against podocyte antigens causing in situ immune complex deposition. Much of our understanding of the disease mechanisms underpinning this kidney-limited autoimmune disease originally came from studies of Heymann nephritis, a rat model of PMN, where autoantibodies against megalin produced a similar disease phenotype though megalin is not implicated in human disease. In PMN, the major target antigen was identified to be M-type phospholipase A2 receptor 1 (PLA2R) in 2009. Further utilization of mass spectrometry on immunoprecipitated glomerular extracts and laser micro dissected glomeruli has allowed the rapid discovery of other antigens (thrombospondin type-1 domain-containing protein 7A, neural epidermal growth factor-like 1 protein, semaphorin 3B, protocadherin 7, high temperature requirement A serine peptidase 1, netrin G1) targeted by autoantibodies in PMN. Despite these major advances in our understanding of the pathophysiology of PMN, treatments remain non-specific, often ineffective, or toxic. In this review, we summarize our current understanding of the immune mechanisms driving PMN from animal models and clinical studies, and the implications on the development of future targeted therapeutic strategies.

[14] Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation

  • Authors: Hao Xiong, Jinsheng Guo
  • Year: 2025
  • Venue: Pharmaceuticals
  • URL: https://www.semanticscholar.org/paper/76e92127053136900f7e3f10e2c9278251ced5d2
  • DOI: 10.3390/ph18040507
  • PMID: 40283943
  • PMCID: 12030350
  • Citations: 8
  • Summary: HSC-targeted approaches using specific surface markers and receptors may enable the selective delivery of drugs, oligonucleotides, and therapeutic peptides that exert optimized anti-fibrotic and anti-HCC effects.
  • Evidence snippets:
  • Snippet 1 (score: 0.456) > Significant progress has been made in elucidating the cellular and molecular mechanisms of liver fibrosis; however, only a few findings have been successfully translated into clinical applications. Firstly, the high cost of drug development and target validation necessitates prolonged timelines and substantial financial investment. Secondly, as regulatory requirements become more stringent, there is an increasing demand for drugs with well-defined clinical efficacy and safety profiles. Moreover, the efficacy observed in animal models often fails to fully translate to clinical settings due to differences in pharmacokinetics, extracellular matrix (ECM) cross-linking, and disease pathophysiology. Despite advancements in anti-fibrotic drug development, accurately identifying ideal noninvasive biomarkers for fibrotic activity and establishing consensus on optimal clinical endpoints remain significant challenges [113,114]. > Currently, addressing the underlying cause remains the only proven strategy to halt or reverse liver fibrosis progression, while the development of effective anti-fibrotic therapies continues to pose a major challenge in liver disease management. Over the past few decades, substantial progress has been made in elucidating the cellular and molecular mechanisms underlying liver fibrosis. Liver fibrosis is a complex pathological change involving multiple cells, factors, and pathways, and the study of the cellular and molecular mechanisms of its occurrence and development provides an important theoretical basis and therapeutic target for clinical drug development. It is anticipated that improved animal models and well-designed clinical trials will facilitate the successful translation of anti-fibrotic research into effective clinical treatments in the near future.

[15] From molecular signatures to predictive biomarkers: modeling disease pathophysiology and drug mechanism of action

  • Authors: A. Heinzel, P. Perco, G. Mayer, R. Oberbauer, A. Lukas et al.
  • Year: 2014
  • Venue: Frontiers in Cell and Developmental Biology
  • URL: https://www.semanticscholar.org/paper/36d6c03a528c1358c0ae5b667cca5ce73b2fbee5
  • DOI: 10.3389/fcell.2014.00037
  • PMID: 25364744
  • PMCID: 4207010
  • Citations: 23
  • Summary: This work exemplifies a computational workflow for expanding from statistics-based association analysis toward deriving molecular pathway and process models for characterizing phenotypes and drug mechanism of action, in turn providing precision medicine hypotheses utilizing predictive biomarkers.
  • Evidence snippets:
  • Snippet 1 (score: 0.455) > In such scenario a biomarker needs to serve as proxy of key mechanistic factors characterizing and driving a disease on a patient-specific level, combined with educating on the specific interference of disease mechanism with drug mechanism of action. For capturing these constraints a detailed molecular map of a clinical phenotype and its interference with a drug mechanism of action is needed, and here integration of Omics profiling adds to identifying such mechanisms (Fechete et al., 2011;Mühlberger et al., 2012). > An a priori stratification of patients based on an appropriately chosen biomarker panel reflecting the pathophysiology of a given patient (group) allowing to determine a match with a specific drug's mechanism of action appears as promising approach. As recently discussed by Himmelfarb et al. fresh approaches are critical in finding therapies to kidney disease benefiting patients, outlining the importance of improving the translational aspect in clinical research (Himmelfarb and Tuttle, 2013). Here, omics technologies have added significantly to the data landscape characterizing chronic kidney disease, however, in a first instance mainly expanding the candidate set of apparently relevant processes and pathways, going in hand with a large number of biomarker candidates, which individually hamper clinically relevant assessment on disease progression (Fechete et al., 2011;Hellemons et al., 2012). > Integrative approaches in the realm of Systems Biology have been proposed for reaching a consensus description of chronic kidney disease pathophysiology, including molecular models of DN as well as of the reno-cardial axis (He et al., 2012;Komorowsky et al., 2012;Mayer et al., 2012;Heinzel et al., 2013). Still, a translation process needs to be followed, joining disease pathophysiology, stratification markers allowing enrichment strategies, combined with on a molecular mechanistic level matching drugs for allowing precision medicine (Mirnezami et al., 2012). In this work we exemplify such procedure on DN being the major clinical presentation leading to end stage renal disease.
  • Snippet 2 (score: 0.444) > Omics profiling significantly expanded the molecular landscape describing clinical phenotypes. Association analysis resulted in first diagnostic and prognostic biomarker signatures entering clinical utility. However, utilizing Omics for deepening our understanding of disease pathophysiology, and further including specific interference with drug mechanism of action on a molecular process level still sees limited added value in the clinical setting. We exemplify a computational workflow for expanding from statistics-based association analysis toward deriving molecular pathway and process models for characterizing phenotypes and drug mechanism of action. Interference analysis on the molecular model level allows identification of predictive biomarker candidates for testing drug response. We discuss this strategy on diabetic nephropathy (DN), a complex clinical phenotype triggered by diabetes and presenting with renal as well as cardiovascular endpoints. A molecular pathway map indicates involvement of multiple molecular mechanisms, and selected biomarker candidates reported as associated with disease progression are identified for specific molecular processes. Selective interference of drug mechanism of action and disease-associated processes is identified for drug classes in clinical use, in turn providing precision medicine hypotheses utilizing predictive biomarkers.

[16] Screening and Analysis of Key Genes in miRNA-mRNA Regulatory Network of Membranous Nephropathy

  • Authors: Yawei Hou, Yameng Li, Yichuan Wang, Wenpu Li, Zhenwei Xiao
  • Year: 2021
  • Venue: Journal of Healthcare Engineering
  • URL: https://www.semanticscholar.org/paper/5b503266a2d3bf122032014fb94e36f17b57080e
  • DOI: 10.1155/2021/5331948
  • PMID: 34824764
  • PMCID: 8610666
  • Citations: 5
  • Summary: The miRNA regulatory network genes may participate in the regulation of podocyte autophagy, lipid metabolism, and renal fibrosis through mTOR, PDGFR-β, LKB1, and VEGF/VEGFR signaling pathways, thereby affecting the occurrence and development of membranous nephropathy.
  • Evidence snippets:
  • Snippet 1 (score: 0.452) > biopsy cannot be performed in some patients due to various reasons, there are certain limitations in clinical applications. erefore, exploring the potential regulatory mechanism of MN and identifying new potential biomarkers and drug target genes have important guiding significance for subsequent clinical diagnosis and treatment. > MicroRNA is a type of endogenous noncoding smallmolecule single-stranded RNA widely found in eukaryotes. It usually consists of 21-25 nucleotides and is highly conserved. It does not have an open reading frame itself. It participates in post-transcriptional gene regulation, affects the pathophysiological process of the body, and is related to cell development, differentiation, proliferation, apoptosis, immune regulation, tumorigenesis, etc. [9]. e study [10] found that, compared with the healthy group, the expression of miRNA-186 in the kidney tissue of patients with membranous nephropathy was significantly downregulated, and in vitro experiments proved that miRNA-186 via Toll-like receptor 4 (TLR4), P2X7, and caspase-3 participates in podocyte apoptosis, leading to increased basement membrane permeability, which in turn leads to membranous nephropathy. e study [9] found that, compared with healthy persons, increased levels of miRNA-193a were found in the urine of membranous nephropathy patients and are associated with an increase in urinary protein levels, thus increasing the severity of the disease. In addition, overexpression of miRNA-193a often indicates poor prognosis. However, there are few reports about the miRNA-miRNA regulatory network and the deep molecular mechanism of MN, especially the miRNA-mediated regulatory mechanism and the molecular network involved in the prevention and treatment of MN are still unclear. Hence, the experiment intends to use the MN-related miRNA and mRNA expression data sets in the GEO database to construct a miRNA-mRNA regulatory network using bioinformatics methods, screen key miRNA-mRNA regulatory relationship pairs, and analyze target functions and related signal pathways to explore their mechanism of action and provide important theoretical references and scientific basis for early diagnosis and targeted therapy of MN.

[17] Gene Expression as a Guide to the Development of Novel Therapies in Primary Glomerular Diseases

  • Authors: P. Garantziotis, S. Doumas, Ioannis Boletis, E. Frangou
  • Year: 2021
  • Venue: Journal of Clinical Medicine
  • URL: https://www.semanticscholar.org/paper/773b7048c3ca5e4e2c851f6bfcc5c03c68946ec9
  • DOI: 10.3390/jcm10112262
  • PMID: 34073694
  • PMCID: 8197155
  • Citations: 1
  • Summary: Novel drugs and small-molecule compounds that may reverse each glomerulonephritis phenotype are identified, suggesting they should be further tested as precise therapy in primary glomerular diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.448) > Primary glomerulonephritides encompass a heterogeneous group of glomerular diseases characterized by abnormal activation of innate and/or adaptive immune responses due to kidney-intrinsic factors [1]. Although relatively rare, they represent the most common cause of end-stage renal disease in young adults and are associated with increased morbidity, mortality and healthcare costs [2]. Current clinicopathological classification includes minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), immunoglobulin and complement-mediated glomerular diseases with a membranoproliferative glomerular pattern (MPGN), immunoglobulin A nephropathy (IgAN) and thin basement membrane nephropathy (TBMN) [1]. Despite improvements in understanding the underlying pathogenic mechanism of each glomerular disease, therapy still remains nonspecific and includes general supportive measures coupled with immunosuppression [3,4]. Disease-specific therapy targeting kidney-intrinsic injury still remains a major challenge in nephrology. > Recent advances in omics technologies have provided insights into the molecular mechanisms underlying complex traits, such as glomerular diseases. Gene expression represents the intermediate phenotype between genetic variation and disease phenotypic variation and thus may inform about genetic and environmental effects on cells and tissues. Specifically, the comparison of gene expression variation between distinct conditions can delineate transcriptional differences and specific molecular pathways [5]. To this end, highthroughput genome-wide gene expression studies have described the transcriptome of the peripheral blood and kidneys of animal models and patients with glomerular diseases and uncovered molecular pathways implicated in their pathogenesis [6]. However, gene expression patterns unique to each primary glomerular disease remain to be defined. > Computational systems biology combines knowledge-driven experimental data with simulation-based analyses and tests hypotheses with in silico experiments. This provides a powerful tool to understand complex biological processes and identify novel drugs or drugs to be repurposed [7].

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.