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The American Journal of the Medical... Feb 2021Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is a leading cause of chronic kidney disease and progresses to end-stage... (Review)
Review
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is a leading cause of chronic kidney disease and progresses to end-stage kidney disease in up to 40% of patients about 20 years after diagnosis. Additionally, IgAN is associated with significant mortality. The diagnosis currently necessitates a kidney biopsy, as no biomarker sufficiently specific and sensitive is available to supplant the procedure. Patients display significant heterogeneity in the epidemiology, clinical manifestations, renal progression, and long-term outcomes across diverse racial and ethnic populations. Recent advances in understanding the underlying pathophysiology of the disease have led to the proposal of a four-hit hypothesis supporting an autoimmune process. To date, there is no disease-specific treatment but, with a better understanding of the disease pathogenesis, new therapeutic approaches are currently being tested in clinical trials. In this review, we examine the multiple facets and most recent advances of this interesting disease.
Topics: Animals; Glomerulonephritis, IGA; Humans; Vasculitis
PubMed: 33309134
DOI: 10.1016/j.amjms.2020.10.003 -
Nature Reviews. Immunology Jul 2023'Glomerulonephritis' (GN) is a term used to describe a group of heterogeneous immune-mediated disorders characterized by inflammation of the filtration units of the... (Review)
Review
'Glomerulonephritis' (GN) is a term used to describe a group of heterogeneous immune-mediated disorders characterized by inflammation of the filtration units of the kidney (the glomeruli). These disorders are currently classified largely on the basis of histopathological lesion patterns, but these patterns do not align well with their diverse pathological mechanisms and hence do not inform optimal therapy. Instead, we propose grouping GN disorders into five categories according to their immunopathogenesis: infection-related GN, autoimmune GN, alloimmune GN, autoinflammatory GN and monoclonal gammopathy-related GN. This categorization can inform the appropriate treatment; for example, infection control for infection-related GN, suppression of adaptive immunity for autoimmune GN and alloimmune GN, inhibition of single cytokines or complement factors for autoinflammatory GN arising from inborn errors in innate immunity, and plasma cell clone-directed or B cell clone-directed therapy for monoclonal gammopathies. Here we present the immunopathogenesis of GN and immunotherapies in use and in development and discuss how an immunopathogenesis-based GN classification can focus research, and improve patient management and teaching.
Topics: Humans; Glomerulonephritis; Adaptive Immunity; Immunity, Innate; Cytokines; Immunotherapy
PubMed: 36635359
DOI: 10.1038/s41577-022-00816-y -
Kidney International Oct 2021The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The...
The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The aim is to assist clinicians caring for individuals with glomerulonephritis (GN), both adults and children. The scope includes various glomerular diseases, including IgA nephropathy and IgA vasculitis, membranous nephropathy, nephrotic syndrome, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infection-related GN, antineutrophil cytoplasmic antibody (ANCA) vasculitis, lupus nephritis, and anti-glomerular basement membrane antibody GN. In addition, this guideline will be the first to address the subtype of complement-mediated diseases. Each chapter follows the same format providing guidance related to diagnosis, prognosis, treatment, and special situations. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on evidence syntheses, with useful infographics incorporating views from experts in the field. Another aim is to propose research recommendations for areas where there are gaps in knowledge. The guideline targets a broad global audience of clinicians treating GN while being mindful of implications for policy and cost. Development of this guideline update followed an explicit process whereby treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, with areas of future research also presented.
Topics: Adult; Child; Glomerulonephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Humans; Kidney; Nephrosis, Lipoid
PubMed: 34556300
DOI: 10.1016/j.kint.2021.05.015 -
Journal of Veterinary Internal Medicine 2013Standard therapy forms the basic foundation for care of dogs with glomerular disease, as it is herein recommended for use in all affected animals regardless of causation...
Standard therapy forms the basic foundation for care of dogs with glomerular disease, as it is herein recommended for use in all affected animals regardless of causation of the disease. Consensus recommendations target the evaluation and management of proteinuria, inhibition of the renin-angiotensin-aldosterone system, modification in dietary intake with special consideration for those nutrients with renal effects, diagnosis and treatment of systemic hypertension, and evaluation and management of body fluid volume status in dogs with glomerular disease.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Consensus; Dog Diseases; Dogs; Glomerulonephritis; Mineralocorticoid Receptor Antagonists; Renin-Angiotensin System
PubMed: 24635378
DOI: 10.1111/jvim.12230 -
Seminars in Immunology Oct 2019Glomerulonephritis (GN) refers to a group of renal diseases affecting the glomeruli due to the damage mediated by immunological mechanisms. A large proportion of the... (Review)
Review
Glomerulonephritis (GN) refers to a group of renal diseases affecting the glomeruli due to the damage mediated by immunological mechanisms. A large proportion of the disease manifestations are caused by disturbances in the complement system. They can be due to genetic errors, autoimmunity, microbes or abnormal immunoglobulins, like modified IgA or paraproteins. The common denominator in most of the problems is an overactive or misdirected alternative pathway complement activation. An assessment of kidney function, amount of proteinuria and hematuria are crucial elements to evaluate, when glomerulonephritis is suspected. However, the cornerstones of the diagnoses are renal biopsy and careful examination of the complement abnormality. Differential diagnostics between the various forms of GN is not possible based on clinical features, as they may vary greatly. This review describes the known mechanisms of complement dysfunction leading to different forms of primary GN (like IgA glomerulonephritis, dense deposit disease, C3 glomerulonephritis, post-infectious GN, membranous GN) and differences to atypical hemolytic uremic syndrome. It also covers the basic elements of etiology-directed therapy and prognosis of the most common forms of GN. Common principles in the management of GN include treatment of hypertension and reduction of proteinuria, some require immunomodulating treatment. Complement inhibition is an emerging treatment option. A thorough understanding of the basic disease mechanism and a careful follow-up are needed for optimal therapy.
Topics: Animals; Bacterial Infections; Biomarkers; Complement Activation; Complement System Proteins; Disease Susceptibility; Glomerulonephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Hemolytic-Uremic Syndrome; Humans
PubMed: 31711769
DOI: 10.1016/j.smim.2019.101331 -
Kidney International May 2013In the past, most cases of bacterial infection-related glomerulonephritis (IRGN) occurred in children following streptococcal upper respiratory tract or skin infections... (Review)
Review
In the past, most cases of bacterial infection-related glomerulonephritis (IRGN) occurred in children following streptococcal upper respiratory tract or skin infections and were called postinfectious GN. Over the past 3 decades, there has been an important shift in epidemiology, bacteriology, and outcome of IRGN. A significant percentage of cases now target adults, particularly the elderly or immunocompromised. Because adult infections are often ongoing at the time of diagnosis, the term IRGN appears more appropriate. The sites of infection in adult IRGN are more heterogeneous than in children, and include the upper respiratory tract, skin, lung, heart, urinary tract, teeth/oral mucosa, and bone. In adults, the disease is more likely to be secondary to non-streptococcal infections, particularly staphylococcal infection. In contrast to the favorable course in children, a significant proportion of adults with IRGN, especially the elderly and diabetics, do not recover renal function. Whereas the pathogenesis of post-streptococcal glomerulonephritis has been studied extensively, leading to the identification of two candidate nephritogenic streptococcal antigens, glyceraldehyde-3-phosphate dehydrogenase and pyrogenic exotoxin B, few investigations have focused on IRGN caused by other bacteria. This review will address the current status of sporadic bacterial IRGN in adults.
Topics: Adult; Age Factors; Aged; Bacterial Infections; Female; Glomerulonephritis; Humans; Male; Middle Aged; Prognosis; Risk Factors
PubMed: 23302723
DOI: 10.1038/ki.2012.407 -
Missouri Medicine 2011Because the differential diagnosis for glomerulonephritis (GN) is broad, using a classification schema is helpful to narrow the causes of GN in a systematic manner. The... (Review)
Review
Because the differential diagnosis for glomerulonephritis (GN) is broad, using a classification schema is helpful to narrow the causes of GN in a systematic manner. The etiology of glomerulonephritis can be classified by their clinical presentation (nephrotic, nephritic, rapidly progressive GN, chronic GN) or by histopathology. GN may be restricted to the kidney (primary glomerulonephritis) or be a secondary to a systemic disease (secondary glomerulonephritis). The nephrotic syndrome is defined by the presence of heavy proteinuria (protein excretion greater than 3.0 g/24 hours), hypoalbuminemia (less than 3.0 g/dL), and peripheral edema. Hyperlipidemia and thrombotic disease may be present. The nephritic syndrome is associated with hematuria and proteinuria and abnormal kidney function and carries poorer prognosis and is typically associated with hypertension. The predominant cause of the nephrotic syndrome in children is minimal change disease. The most common causes of nephritic syndrome are post infectious GN, IgA nephropathy and lupus nephritis. Chronic GN is slowly progressive and is associated with hypertension and gradual loss of kidney function. Treatment includes non-specific measure aimed at controlling hypertension, edema, proteinuria and disease modifying immunosuppression.
Topics: Glomerulonephritis; Hematuria; Humans; Kidney Diseases; Nephrology; Nephrotic Syndrome
PubMed: 21462608
DOI: No ID Found -
Kidney International Dec 2013C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty...
C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition. This meeting report represents the current consensus view of the group.
Topics: Biomedical Research; Biopsy; Complement C3; Cooperative Behavior; Glomerulonephritis; Humans; International Cooperation; Kidney Glomerulus; Predictive Value of Tests; Prognosis
PubMed: 24172683
DOI: 10.1038/ki.2013.377 -
BMC Nephrology May 2020Glomerulonephritides (GN) are relatively rare kidney diseases with substantial morbidity and mortality. They are often difficult to treat, sometimes with no cure, and...
BACKGROUND
Glomerulonephritides (GN) are relatively rare kidney diseases with substantial morbidity and mortality. They are often difficult to treat, sometimes with no cure, and can lead to chronic kidney disease (CKD) and end stage kidney disease (ESKD). Kidney biopsy is the diagnostic procedure of choice with variable indications from center to center. It helps in identifying the exact specific diagnosis, assessing the level of disease activity and severity, and hence aids in proper therapy and helps predicting prognosis. There is a global change of pattern of glomerular disease over the last five decades.
METHODS
Retrospective analysis of all kidney biopsies (545 cases) that were done in patients over 12 year-old over last six years in four major hospitals in Kuwait. The indications for kidney biopsy were categorized into six clinical syndromes: nephrotic syndrome, sub-nephrotic proteinuria, nephrotic syndrome plus acute kidney injury (AKI), sub-nephrotic proteinuria plus AKI, isolated hematuria, and Unexplained renal impairment. We calculated the incidence of each type of kidney disease and indication of biopsy.
RESULTS
most common indication of kidney biopsy was sub-nephrotic proteinuria associated with AKI in 179 cases (32.8%). Primary Glomerulonephritis was the main diagnosis that was reported in 356 cases (65.3%). Immunoglobulin A Nephropathy (IgAN) was the commonest lesion in primary glomerulonephritis in 85 (23.9%) cases. Secondary Glomerulonephritis was diagnosed in 134 cases (24.6%), 56 (41.8%) of them were reported as lupus nephritis cases. In young adults (below 18 years of age) there were 31 cases reviews, 35.5% were found to have minimal change disease (MCD).
CONCLUSION
IgAN is the commonest glomerulonephritis in primary nephrotic syndromes in Kuwait over the past six years. Lupus nephritis is the leading secondary glomerulonephritis diagnosis.
Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Child; Diabetic Nephropathies; Female; Glomerulonephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Hematuria; Humans; Kuwait; Lupus Nephritis; Male; Middle Aged; Nephritis, Interstitial; Nephrosis, Lipoid; Nephrotic Syndrome; Proteinuria; Thrombotic Microangiopathies; Time Factors; Young Adult
PubMed: 32423387
DOI: 10.1186/s12882-020-01836-3 -
Nephron 2020C3 glomerulopathy (C3G) is a clinicopathologic entity secondary to dysregulation of the alternative complement pathway in plasma and the glomerular microenvironment. The... (Review)
Review
C3 glomerulopathy (C3G) is a clinicopathologic entity secondary to dysregulation of the alternative complement pathway in plasma and the glomerular microenvironment. The current consensus definition of C3G relies on immunofluorescence staining criteria. However, due to its high clinical variability, these criteria may not be accurate enough in some clinical scenarios. Thus, a new pathogenic classification based on a cluster analysis of clinical, histologic, and genetic data has recently been proposed, which could also help identify patients at higher risk of progression. Several pathogenic abnormalities in complement genes have been described, and the role of autoantibodies in the disease is increasingly recognized, but still the genotype-phenotype correlations in C3G are poorly understood. C3G may be diagnosed in both children and adults. The spectrum of clinical manifestations is wide, although one of the most common clinical presentations is proteinuria with relatively preserved kidney function. In order to standardize the evaluation of kidney biopsies from these patients, a histopathologic index was recently proposed, including both parameters of activity and chronicity. However, this index has not yet been validated in independent cohorts. Currently, no targeted therapies are available in clinical settings for the treatment of C3G, although several new molecules are under investigation. Treatment with corticosteroids plus mycophenolate mofetil has been shown to be associated with improved renal outcomes, as compared to other immunosuppressive regimens. Yet, the main determinants of treatment response with this regimen and the influence of the underlying pathogenic drivers have not been extensively studied. The therapeutic response to eculizumab, an anti-C5 monoclonal antibody, has been shown to be highly heterogeneous. Thus, its current clinical indication in C3G is restricted to rapidly progressive forms of the disease. To summarize, in recent years, several important advances have taken place in the understanding of C3G, but still further studies are warranted to elucidate the best therapeutic strategies that could improve prognosis of this entity.
Topics: Adult; Child; Complement C3; Glomerulonephritis; Humans
PubMed: 32369815
DOI: 10.1159/000507254