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- Acute glomerulonephritis (GN) is an inflammatory process involving the glomerulus of the kidney, resulting in a clinical syndrome consisting of hematuria, proteinuria, and renal insufficiency, often in association with hypertension and edema.
- Acute GN may be caused by primary glomerular disease or secondary to systemic disease.
- Infection-related GN (also postinfectious GN)
- IgA nephropathy/Henoch-Schönlein purpura (HSP)
- Antiglomerular basement membrane disease (anti-GBM disease)
- Antineutrophil cytoplasmic antibody (ANCA)-associated GN
- Membranoproliferative GN (MPGN)
- Lupus nephritis
- Cryoglobulin-associated GN
- Clinical severity ranges from asymptomatic microscopic or gross hematuria to a rapid loss of kidney function over days to weeks, termed rapidly progressive GN (RPGN).
- In patients with RPGN, kidney biopsy often demonstrates crescentic GN, which usually warrants urgent and aggressive treatment.
Urgent investigation and treatment are required to avoid irreversible loss of kidney function.
- Infection-related GN
- Most commonly manifests after resolution of group A β-hemolytic Streptococcus infection (poststreptococcal)
- Can also occur as a result of other bacterial infections, such as infective endocarditis or shunt nephritis, or less commonly with viral or parasitic infections
- Accounts for 80% of acute GN in children
- IgA nephropathy
- Most common primary GN in the world
- Most common in the 2nd and 3rd decades but can occur at any age
- Incidence differs geographically: Asia > United States
- Populations of East Asian ancestry are at increased risk for IgA nephropathy, and some genetic factors have been identified.
- HSP, the form with extrarenal manifestations, can occur at any age but typically occurs in children <10 years old.
- Anti-GBM disease
- Can cause Goodpasture disease, a notable cause of the pulmonary–renal syndrome
- Peak distribution in 3rd and 6th decades
- ANCA-associated GN
- Often has a relapsing and remitting course
- Four disease presentations:
- Granulomatosis with polyangiitis (GPA), formerly Wegener granulomatosis
- Microscopic polyangiitis (MPA)
- Isolated pauci-immune GN—when isolated to kidneys
- Eosinophilic GPA, formerly Churg-Strauss disease—GN relatively common but renal involvement rarely severe
- Older patients are more commonly affected, although this GN can affect any age group.
- May be primary (idiopathic) or secondary to systemic diseases
- Epidemiology varies depending on the mechanism of injury.
- Lupus nephritis
- 30–70% of systemic lupus patients will have renal involvement.
- Incidence of lupus nephritis is higher among African Americans in comparison to white Caucasian populations.
- Cryoglobulin-associated vasculitis
- 80% of cases with hepatitis C virus infection
- May also be associated with autoimmune disease or dysproteinemia
Etiology and Pathophysiology
- In general, systemic and/or local immune activation causes glomerular injury.
- Immune-complex mediated: from antigen–antibody formation and deposition in the kidneys
- Postinfectious GN: host immune reaction to nephritogenic streptococci strains as a trigger
- IgA nephropathy: abnormal glycosylation of IgA, leads to its mesangial deposition; etiology poorly understood
- MPGN: typically secondary to systemic diseases, such as chronic infections (hepatitis C), autoimmune diseases, monoclonal gammopathies, and complement dysregulation
- Lupus nephritis: autoimmune disease
- Cryoglobulin-associated GN: inflammation from complexes known as cryoglobulins, named for their property of precipitating as lower temperatures
- Direct antibody-mediated injury:
- Anti-GBM disease: caused by autoantibodies that target type IV collagen of basement membranes
- Pauci-immune GN
- ANCA-associated GN: autoantibodies against neutrophil granules involved in pathogenesis
- Alternative complement pathway dysregulation:
- C3 glomerulopathy: subtype of MPGN with predominant C3 without immunoglobulin staining on immunofluorescence; includes dense deposit disease (DDD) and C3GN
Genetic factors are likely to play a role in susceptibility to many of the acute GNs, although these have not been sufficiently defined to be clinically useful in most circumstances.
- Epidemics of nephritogenic strains of streptococci are triggers for postinfectious GN.
- Anti-GBM disease has been associated with prior pulmonary injury and inhalation exposures, such as hydrocarbon solvents.
- ANCA-associated GN may be drug induced (e.g., hydralazine, levamisole-contaminated cocaine) and is also associated with environmental exposures such as silica.
- Infection with hepatitis B or C is associated with MPGN.
- Infection with hepatitis C is a risk factor for developing cryoglobulinemic GN.
- Mutations in alternate complement pathway genes are associated with increased risk of developing complement-mediated MPGN.
Early detection is paramount.