What is the appropriate management for a patient with an elevated C3 complement level?

Management of Elevated C3 Complement Level (195)

Elevated C3 complement levels require a comprehensive diagnostic evaluation to identify underlying causes, with management focused on treating the primary condition rather than the complement abnormality itself.

Diagnostic Approach for Elevated C3

Initial Evaluation

• Complete blood count with differential (to detect eosinophilia or leukopenia)
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
• Renal function tests (serum creatinine, eGFR, urinalysis, urine protein/creatinine ratio)
• Complement panel (C3, C4, CH50)
• Thyroid function tests and thyroid autoantibodies

Consider Underlying Causes

1. Acute phase reaction

   • Infections
   • Inflammatory conditions
   • Tissue injury

2. Autoimmune disorders

   • Systemic lupus erythematosus (SLE)
   • Rheumatoid arthritis
   • Sjögren's syndrome

3. Immune complex-mediated glomerulonephritis (ICGN)

   • Evaluate for proteinuria and hematuria
   • Consider renal biopsy if clinical suspicion is high

4. Hepatic disorders

   • Autoimmune hepatitis
   • Viral hepatitis (HBV, HCV)

5. Monoclonal gammopathies

   • Especially in patients over 50 years old
   • Consider serum and urine protein electrophoresis

Management Strategy

For Immune Complex-Mediated Glomerulonephritis

• If ICGN with nephrotic syndrome and normal/near-normal creatinine:
  • Consider limited course of glucocorticoids as first-line therapy 1
  • Avoid calcineurin inhibitors due to risk of thrombotic microangiopathy 1

For Specific Conditions

MPGN/C3 Glomerulopathy

• For moderate-to-severe disease: MMF plus glucocorticoids 2
• If MMF fails: Consider eculizumab 2
• For severe forms with crescents or RPGN: Aggressive immunosuppression similar to ANCA-associated vasculitis 2

Hepatitis-Related GN

• For HBV-related GN: Nucleoside analogues (tenofovir or entecavir) or interferon-alpha 2
• For HCV-related GN: Pegylated interferon with doses adjusted to kidney function 2

Supportive Care

• For patients with eGFR <30 ml/min/1.73m² without active necrotizing or crescentic GN: Supportive care alone 2
• RAS inhibition for patients with proteinuria <3.5 g/day and normal eGFR 1

Monitoring and Follow-up

• Serial measurements of C3 levels are more valuable than single measurements 1
• Monitor renal function and proteinuria regularly
• Adjust therapy based on clinical response and complement levels

Special Considerations

• Elevated C3 has been associated with prehypertension and may require blood pressure monitoring 3
• Consider clinical trials for refractory cases, especially for C3 glomerulopathy 2
• Patients with persistently low C3 beyond 12 weeks may require kidney biopsy to exclude C3 glomerulonephritis 2

Clinical Pearls

• C3 is a positive acute-phase reactant that responds sluggishly (days rather than hours) to inflammatory stimuli 4
• Normal reference ranges for C3 vary slightly with age and gender 4
• Trends in C3 levels over time are more clinically meaningful than isolated measurements 1
• Treatment should target the underlying cause rather than the complement abnormality itself 1