What is the typical clinical presentation of ANCA (Antineutrophil Cytoplasmic Antibody)-associated nephritic syndrome?

Clinical Presentation of ANCA-Associated Nephritic Syndrome

ANCA-associated nephritic syndrome typically presents with a rapid decline in kidney function, hematuria, proteinuria, and often hypertension, representing a medical emergency that requires prompt diagnosis and treatment to prevent irreversible kidney damage and mortality.1

Key Clinical Features

Renal Manifestations

• Rapidly progressive glomerulonephritis (RPGN) - the most common presentation
• Rapid decline in kidney function (rising serum creatinine)
• Hematuria (microscopic or gross)
• Proteinuria (variable, seen in most patients)
• Hypertension
• Oliguria or anuria in severe cases

Laboratory Findings

• Positive ANCA serology (MPO-ANCA or PR3-ANCA)
• Elevated inflammatory markers (e.g., C-reactive protein)
• Elevated serum creatinine
• Abnormal urinalysis showing:
  • Dysmorphic red blood cells
  • Red blood cell casts
  • Glomerular hematuria
  • Pyuria without infection1

Extrarenal Manifestations

Depending on the specific ANCA-associated vasculitis syndrome, patients may present with:

• Pulmonary manifestations (diffuse alveolar hemorrhage in 30% of cases)
• Upper respiratory tract involvement (sinusitis, otitis)
• Skin lesions (purpura, nodules)
• Neurological symptoms (mononeuritis multiplex)
• Constitutional symptoms (fever, weight loss, fatigue)1, 2

Diagnostic Approach

When a patient presents with rapidly declining kidney function and urinalysis positive for protein and blood, the following diagnostic algorithm should be followed:

1. Confirm glomerular hematuria and/or pyuria without infection
2. Evaluate for extrarenal signs/symptoms
3. Obtain autoimmune serologies (ANCA, ANA, anti-GBM antibodies, complement)
4. Exclude infection
5. Obtain kidney biopsy if feasible1

Histopathological Findings

Kidney biopsy typically reveals:

• Pauci-immune necrotizing and crescentic glomerulonephritis
• Classification based on predominant glomerular pattern:
  • Focal: ≥50% normal glomeruli
  • Crescentic: ≥50% glomeruli with cellular crescents
  • Sclerotic: ≥50% globally sclerotic glomeruli
  • Mixed: no predominant pattern1

Prognostic Factors

Factors associated with poorer outcomes include:

• Older age
• Pulmonary hemorrhage
• Dialysis dependence at presentation
• Lower percentage of normal glomeruli
• Greater extent of tubular atrophy and interstitial fibrosis3, 4

Important Clinical Considerations

• Persistent hematuria and proteinuria are seen in approximately 50% of patients even after treatment and don't necessarily indicate active disease1
• A return or increase of hematuria with proteinuria after initial resolution may indicate kidney relapse1
• The persistence of ANCA positivity, an increase in ANCA levels, or a change from negative to positive ANCA may predict future disease relapse1
• Kidney recovery can occur even with advanced kidney damage, so induction treatment should not be withheld based solely on unfavorable histologic findings1

Pitfalls to Avoid

1. Delayed diagnosis and treatment - Because of the potential severity of AAV, if clinical presentation is compatible with small-vessel vasculitis and ANCA serology is positive, treatment should not be delayed while waiting for kidney biopsy results1

2. Overlooking dual antibody positivity - Some patients may have both ANCA and anti-GBM antibodies (approximately 30% of cases), which affects treatment approach2

3. Misinterpreting persistent hematuria/proteinuria - These findings don't necessarily indicate active disease if serum creatinine is stable or improving1

4. Failure to distinguish from other causes of rapidly progressive glomerulonephritis - Other conditions like anti-GBM disease and lupus nephritis can present similarly1, 2

Early recognition of this clinical presentation is crucial as prompt immunosuppressive treatment significantly improves survival, even in older adults (>75 years) and those with severe kidney involvement1.