What is Glomerulonephritis?

Glomerulonephritis: Definition, Classification, and Management

Glomerulonephritis is a heterogeneous group of disorders characterized by inflammation of the glomeruli (kidney filtration units), presenting with variable combinations of hematuria, proteinuria, hypertension, and reduced kidney function. 1

Classification of Glomerulonephritis

Glomerulonephritis can be classified based on immunopathogenesis into five main categories:

• Immune-complex mediated glomerulonephritis: Including infection-related glomerulonephritis, IgA nephropathy, lupus nephritis, and cryoglobulinemic glomerulonephritis 1
• Anti-neutrophil cytoplasmic antibodies (ANCA)-associated (pauci-immune) glomerulonephritis 1
• Anti-glomerular basement membrane (anti-GBM) glomerulonephritis 2
• C3 glomerulopathy: Characterized by dominant C3 deposits with minimal or no immunoglobulin deposits 2
• Monoclonal immunoglobulin-associated glomerulonephritis: Including various forms of monoclonal gammopathy of renal significance (MGRS) 3

Clinical Presentation

Glomerulonephritis can present with:

• Nephritic syndrome: Characterized by hematuria, edema, hypertension, and variable degrees of renal impairment 4
• Rapidly progressive glomerulonephritis: Rapid decline in renal function over days to weeks 1
• Asymptomatic hematuria and proteinuria: Most common presentation 1
• Disease flares: Particularly common in IgA nephropathy and C3 glomerulopathy 1

Pathophysiology

The underlying mechanisms of glomerulonephritis vary by type:

• Post-streptococcal glomerulonephritis: Immune complex deposition following streptococcal infection causes inflammation and kidney damage 5
• ANCA-associated vasculitis: Autoantibodies target neutrophil components, leading to neutrophil activation and vascular damage 2
• Anti-GBM disease: Autoantibodies target the glomerular basement membrane, causing linear IgG deposits 2
• Monoclonal gammopathy-related glomerulonephritis: Deposition of monoclonal immunoglobulins in various renal compartments 3

Specific Types of Glomerulonephritis

Infection-Related Glomerulonephritis

• Post-streptococcal glomerulonephritis: Follows streptococcal infection, with immune complex deposition in glomerular tissue 5
• Cryoglobulinemic glomerulonephritis: Often associated with HCV infection, characterized by cryoglobulin deposition 3

Monoclonal Gammopathy-Related Glomerulonephritis

• Monoclonal immunoglobulin deposition disease (MIDD): Affects all renal compartments with non-organized deposits 3
• Immunoglobulin-related amyloidosis: Characterized by fibrillar deposits that stain with Congo red 3
• Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID): Deposits confined to glomeruli 3
• Cryoglobulinemic glomerulonephritis: Features microtubular immunoglobulin deposits 3

Other Important Types

• IgA Nephropathy: Characterized by mesangial IgA deposits 2
• Lupus Nephritis: Glomerular involvement in systemic lupus erythematosus 2
• C3 Glomerulopathy: Includes dense deposit disease and C3 GN 2

Diagnostic Approach

• Kidney biopsy: Gold standard for diagnosis, providing information on:

  • Pattern of injury
  • Immunofluorescence findings
  • Electron microscopy findings 2, 1

• Serological testing:

  • Anti-GBM antibodies
  • ANCA
  • Anti-nuclear antibodies
  • Complement levels
  • Specific autoantibodies 2

• Urinalysis: Evaluation for hematuria, proteinuria, and urinary sediment 4

Treatment Principles

Treatment approaches vary by specific glomerular disease:

• Post-streptococcal glomerulonephritis:

  • Antibiotics to eliminate streptococcal infection
  • Supportive care including diuretics and antihypertensives
  • Corticosteroids reserved for severe crescentic glomerulonephritis 5

• Cryoglobulinemic nephritis:

  • For diffuse membranoproliferative glomerulonephritis: Immunomodulating treatment including glucocorticoids, immunosuppressive agents, and plasma exchange
  • For mesangial glomerulonephritis: Direct-acting antiviral therapy as first-line approach 3

• Monoclonal gammopathy-related glomerulonephritis:

  • Treatment directed at the underlying B-cell or plasma cell clone 3

Prognostic Factors

• Poor prognostic indicators:

  • Presence of crescents
  • Severe interstitial fibrosis and tubular atrophy
  • High-grade proteinuria
  • Creatinine value >1.5 mg/dL at the time of renal biopsy 3, 2

• Leading cause of death: Cardiovascular disease (over 60% of cases) 3

Common Pitfalls and Caveats

• Misdiagnosis: Some cases of monoclonal gammopathy with findings consistent with C3 glomerulonephritis may actually have membranoproliferative glomerulonephritis with masked monoclonal deposits, requiring additional immunofluorescence studies on protease-digested, paraffin-embedded tissue 3

• Undertreatment: Failure to recognize rapidly progressive forms can lead to irreversible kidney damage 1

• Overtreatment: Mesangial glomerulonephritis in cryoglobulinemic nephritis may be self-limiting and respond to antiviral therapy alone without requiring aggressive immunosuppression 3