What are the primary management strategies for nephritic and nephrotic syndromes?

Management Strategies for Nephritic and Nephrotic Syndromes

The management of nephritic and nephrotic syndromes requires specific therapeutic approaches based on the underlying pathology, with immunosuppressive therapy being the cornerstone of treatment for primary forms while addressing underlying causes in secondary forms. 1

Understanding Nephritic vs. Nephrotic Syndrome

Nephritic Syndrome

• Definition: Characterized by hematuria, proteinuria, hypertension, and often acute kidney injury 2
• Common causes: Post-infectious glomerulonephritis, IgA nephropathy, lupus nephritis, ANCA-associated vasculitis 3
• Clinical presentation: Hematuria, moderate proteinuria, hypertension, edema, abnormal kidney function

Nephrotic Syndrome

• Definition: Characterized by heavy proteinuria (>3.5g/day), hypoalbuminemia (<3.0g/dL), peripheral edema, and often hyperlipidemia 3
• Common causes:
  • Primary: Minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis (FSGS)
  • Secondary: Diabetes mellitus, lupus, amyloidosis, medications 1

Management of Nephrotic Syndrome

1. Supportive Therapy (All Patients)

• Fluid and sodium restriction: To manage edema
• Diuretics: Loop diuretics for edema management
• RAS blockade: ACE inhibitors or ARBs to reduce proteinuria 4
  • Losartan has shown 16% risk reduction in progression of nephropathy in diabetic patients 5
• Lipid management: Statins for hyperlipidemia
• Anticoagulation: Consider in severe cases with hypoalbuminemia due to thrombosis risk

2. Primary Nephrotic Syndrome Management

Minimal Change Disease

• First-line: High-dose oral glucocorticoids 6
  • Children: Prednisone 60 mg/m²/day (max 80 mg) for 4-6 weeks, then 40 mg/m² on alternate days for 4-6 weeks 6
  • Adults: Prednisone 1 mg/kg/day (max 80 mg) for up to 16 weeks 7

Membranous Nephropathy

• First-line options:
  • Rituximab plus supportive therapy 6
  • Cyclophosphamide with oral prednisolone
    • IV cyclophosphamide regimen has shown 74% remission rate within 18 months 8
  • Calcineurin inhibitors (cyclosporine, tacrolimus) 6

Focal Segmental Glomerulosclerosis (FSGS)

• Primary FSGS: High-dose oral glucocorticoids as first-line therapy 6
• FSGS-UC or secondary FSGS: Immunosuppression not recommended; focus on supportive care and treating underlying causes 6

3. Steroid-Resistant or Frequently Relapsing Nephrotic Syndrome

• Second-line agents:
  • Alkylating agents: Cyclophosphamide (2 mg/kg/day for 8-12 weeks, max cumulative dose 168 mg/kg) 6
  • Calcineurin inhibitors: Cyclosporine, tacrolimus
  • Mycophenolate mofetil (MMF) 6
  • Rituximab for specific indications

Management of Nephritic Syndrome

1. General Approach

• Blood pressure control: Essential to prevent further kidney damage
• Immunosuppression: Based on specific diagnosis and severity

2. Disease-Specific Management

Post-infectious Glomerulonephritis

• Supportive care: Blood pressure control, fluid management
• Antibiotics: If ongoing infection
• Usually self-limiting: Most cases resolve spontaneously

IgA Nephropathy

• RAS inhibition: For proteinuria and blood pressure control 6
• Glucocorticoids: For persistent proteinuria despite optimal supportive care 6
• Tonsillectomy: May be considered in selected cases 6

Lupus Nephritis

• Induction therapy: Cyclophosphamide or mycophenolate mofetil with glucocorticoids
• Maintenance therapy: Lower-dose immunosuppression to prevent relapse

ANCA-associated Vasculitis

• Induction: Cyclophosphamide or rituximab with high-dose glucocorticoids
• Maintenance: Azathioprine or rituximab

Special Considerations

Pediatric Patients

• Minimal change disease: Most common cause of nephrotic syndrome in children
• Steroid dosing: Weight-based or body surface area-based dosing 6
• Growth monitoring: Essential during prolonged steroid therapy 9

Elderly Patients

• Dose adjustment: Start at lower doses of immunosuppressants
• Monitoring: Closer monitoring for adverse effects
• Comorbidities: Consider increased risk of diabetes, hypertension, and infections 9

Complications to Monitor and Manage

• Infections: Consider prophylaxis during intense immunosuppression
• Thrombosis: Monitor for venous thromboembolism, especially in nephrotic syndrome
• Bone health: Calcium and vitamin D supplementation during steroid therapy
• Cardiovascular risk: Address modifiable risk factors

When to Refer to Nephrology

• Nephrotic-range proteinuria (>3.5g/day)
• Rapidly progressive glomerulonephritis
• Acute kidney injury
• Uncertainty about diagnosis or management
• Need for renal biopsy
• Consideration of immunosuppressive therapy 4

Common Pitfalls to Avoid

• Treating secondary FSGS with immunosuppression instead of addressing the underlying cause
• Inadequate duration of initial steroid therapy in minimal change disease
• Failure to monitor for and prevent steroid-related complications
• Delaying referral for renal biopsy in adults with nephrotic syndrome
• Not distinguishing between primary and secondary forms before initiating treatment