Description

• Acute glomerulonephritis (GN) is an inflammatory process involving the glomerulus of the kidney, resulting in a clinical syndrome consisting of sudden-onset 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.
• Clinical severity ranges from self-limited asymptomatic microscopic or gross hematuria to a rapidly progressive loss of kidney function over days to weeks, termed rapidly progressive GN (RPGN).

Epidemiology

• Infection-related GN
  • Postinfectious GN most commonly manifests after resolution of group A β-hemolytic Streptococcus infection.
  • Can also occur as a result of other bacterial infections, such as infective endocarditis, VP shunt nephritis, or less commonly with viral, helminthic, or parasitic infections
• IgA nephropathy
  • Most common primary GN in the world
  • Most common in the 2nd and 3rd decades
  • Incidence differs geographically: Asia > United States
  • HSP, the form with extrarenal manifestations, typically occurs in children <10 years old.
• Anti-GBM disease
  • Goodpasture syndrome: a notable cause of 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
• MPGN
  • May be primary or secondary to systemic diseases
  • Epidemiology varies depending on the mechanism of injury and is more often a subacute or chronic presentation
• Lupus nephritis
  • About 60% of systemic lupus patients will have renal involvement.
  • Incidence of lupus nephritis is higher among black and Hispanic populations in comparison to white populations.
  • 6 classes
    • Minimal mesangial disease
    • Mesangial proliferation
    • Focal proliferative (active) and/or sclerosing (chronic) disease
    • Diffuse segmental or global proliferative (active) and/or sclerosing (chronic) disease
    • Membranous lupus nephritis
    • Advanced sclerosis lupus nephritis
• Cryoglobulin-associated vasculitis
  • 80% of cases with hepatitis C virus (HCV) infection
  • May also be associated with autoimmune disease or dysproteinemia

Prevalence

• In patients >65 years of age, with an average age of 75 years, about 1.2% of people are affected by either primary or secondary GN.
• In patients between the ages of 37 and 65 years of age, GN was much less commonly seen, with only about 0.12% of people affected by either primary or secondary GN (1).
• The incidence and prevalence of GN in children is unknown. Acute postinfectious GN is the most common type but has diminished over the years.

Etiology and Pathophysiology

• Systemic and/or local immune activation causes glomerular injury.
• Immune-complex mediated: antigen–antibody formation and deposition in the kidneys. Immune complexes are seen on immunofluorescence.
  • Postinfectious GN
  • IgA nephropathy
  • MPGN
    • Cryoglobulin-associated GN
  • Lupus nephritis
• Direct antibody-mediated injury, linear staining on immunofluorescence
  • Anti-GBM disease
• Pauci-immune GN, not seen on immunofluorescence staining
  • ANCA-associated GN
• Alternative complement pathway dysregulation
  • C3 glomerulopathy

Risk Factors

• 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.
• Hepatitis B is associated with MPGN. Hepatitis C is associated with both MPGN and cryoglobulinemic GN.