Aetiology
The disease can result from kidney-limited glomerulopathy or from glomerulopathy-complicating systemic disease: for example, systemic lupus erythematosus (SLE) and vasculitis.[3]
Glomerular injury may be caused by inflammation due to leukocyte infiltration, antibody deposition, and complement activation. Poorly understood non-inflammatory mechanisms may be responsible for some conditions as well.
It is increasingly possible to identify underlying causes, and idiopathic cases are rare.[3]
Infections (group A beta-haemolytic Streptococcus, respiratory and gastrointestinal infections, hepatitis B and C, endocarditis, HIV, toxaemia, syphilis, schistosomiasis, malaria, and leprosy)
Systemic inflammatory conditions such as vasculitides (SLE, rheumatoid arthritis, anti-glomerular basement membrane disease, granulomatosis with polyangiitis, microscopic polyangiitis, cryoglobulinaemia, IgA vasculitis (Henoch-Schonlein purpura), scleroderma, and haemolytic uraemic syndrome)
Drugs (gold sodium thiomalate, hydralazine, lithium, propylthiouracil, and non-steroidal anti-inflammatory drugs)
Metabolic disorders (diabetes mellitus, hypertension, and thyroiditis)
Malignancy (lung and colorectal cancer, melanoma, and Hodgkin's lymphoma)
Hereditary disorders (Fabry's disease, Alport's syndrome, thin basement membrane disease, nail-patella syndrome, and hereditary complement protein disorders)
Deposition diseases (amyloidosis and monoclonal immunoglobulin deposition disease [MIDD]).
Pathophysiology
Most human glomerulonephritides are triggered by immune-mediated injury exhibiting both cellular (innate) and humoral (adaptive) components.[20]
The cellular immune response contributes to the infiltration of glomeruli by circulating mononuclear inflammatory cells (lymphocytes and macrophages) and crescent formation in the absence of antibody deposition. This mechanism plays a primary role in some types of GN such as minimal change nephrotic syndrome or focal glomerulosclerosis and antineutrophil cytoplasmic antibody-positive GN.[21][22] Some evidence also supports a role for T cells and platelets in glomerular pathology.[23][24]
The humoral immune response leads to immune deposit formation and complement activation in glomeruli.[20][25] Antibodies can be deposited within the glomerulus when circulating antibodies react with intrinsic autoantigens (anti-glomerular basement membrane disease or membranous nephropathy), or with extrinsic antigens that have been trapped within the glomerulus (post-infectious GN), or by trapping of immune complexes that have formed in the systemic circulation (cryoglobulinaemia). Injury usually occurs as a consequence of the activation and release of a variety of inflammatory mediators (complement activation, cytokines, growth factors, and vasoactive agents) that initiate a complex interplay of events that ultimately result in the structural and functional characteristics of immune glomerular disease.[26]
A variety of non-immunological metabolic, haemodynamic, and toxic stresses can also induce glomerular injury. These include hyperglycaemia (diabetic nephropathy), lysosomal enzyme defects, and high intraglomerular pressure (systemic hypertension and overload of functioning nephrons following loss of other nephrons due to other causes). A few glomerular diseases are due to hereditary defects resulting in deformity of the glomerular basement membrane (e.g., type IV collagen disorders).
Classification
Primary/secondary diagnosis[2]
Primary diagnosis: composed of 3 or 4 components in the following order:
Disease entity or pathogenesis/pathogenic type (when specific disease entity is not known)
Pattern of glomerular injury
Scores and/or class of the disease entity where appropriate.
Additional disease-related features.
Secondary diagnoses: may be either related or unrelated to the GN (e.g., diabetic glomerulosclerosis, drug-induced interstitial nephritis, acute tubular injury, atheroembolic disease).
Classification of glomerulonephritis based on cause[3]
A causal approach to the classification of GN is favoured over a pattern-based approach, as the pattern of injury may be the same for different causes, and the same cause may have several patterns of injury.
Immune-complex glomerulonephritis: includes infection-related glomerulonephritis, immunoglobulin A (IgA) nephropathy, lupus nephritis, and cryoglobulinaemic GN
Anti-neutrophil cytoplasmic antibodies (ANCA)-associated (pauci-immune) GN
Anti-glomerular basement membrane (GBM) GN
Monoclonal immunoglobulin-associated GN
C3 glomerulopathy.
Nephrotic/nephritic classification[1][4]
Nephrotic syndrome (proteinuria [protein excretion rate ≥3.5 g per 24 hours or protein:creatinine ratio ≥300 mg/mmol {≥3000 mg/g}], hypoalbuminaemia, hyperlipidaemia, and oedema)
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Membranoproliferative pattern of glomerular injury
Diabetic nephropathy
Lupus nephritis
Monoclonal protein-associated.
Nephritic syndrome (haematuria, sub-nephrotic-range proteinuria, and hypertension)
Immunoglobulin A nephropathy
Post-infectious GN/infection-associated GN
Lupus nephritis
Rapidly progressive GN
Vasculitis
Anti-GBM GN.
Nephritic and rapidly progressive GN (RPGN) classification[5]
Nephritic and RPGN can be classified according to the immunofluorescence microscopy:
Granular immune deposits (immune complex-mediated)
Linear immune deposits (anti-GBM)
Pauci-immune (vasculitis).
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