What is the best course of treatment for a patient with IgA (Immunoglobulin A) nephropathy experiencing vasculitis?

Treatment of IgA Nephropathy with Vasculitis

Treat IgA nephropathy with vasculitis (crescentic IgAN with rapidly progressive renal deterioration) immediately with cyclophosphamide plus glucocorticoids, following the same protocol used for ANCA-associated vasculitis. 1

Defining the Clinical Scenario

The critical first step is determining whether this represents true rapidly progressive crescentic IgAN requiring aggressive immunosuppression:

• Crescentic IgAN is defined as >50% of glomeruli showing crescents on kidney biopsy with rapidly progressive renal deterioration 1
• The presence of crescents alone without concomitant decline in GFR does not constitute rapidly progressive IgAN and requires only close monitoring 1
• If the patient has rapidly declining kidney function with positive ANCA serology alongside IgA deposits, treat immediately without waiting for biopsy confirmation 1, 2

Induction Therapy Regimen

Cyclophosphamide Administration

Choose between intravenous or oral cyclophosphamide based on the following factors 1:

Intravenous cyclophosphamide (preferred for severe disease):

• Dose: 15 mg/kg at weeks 0,2,4,7,10,13 1, 2
• Reduce to 12.5 mg/kg for age >60 years 1
• Reduce to 10 mg/kg for age >70 years 1
• Reduce by 2.5 mg/kg for GFR <30 ml/min/1.73 m² 1

Oral cyclophosphamide (alternative):

• Dose: 2 mg/kg/day (maximum 200 mg/day) for 3-6 months 1, 3
• Reduce to 1.5 mg/kg/day for age >60 years 1
• Reduce to 1.0 mg/kg/day for age >70 years 1
• Reduce by 0.5 mg/kg/day for GFR <30 ml/min/1.73 m² 1

Glucocorticoid Protocol

Use the reduced-dose glucocorticoid regimen from the 2024 KDIGO guidelines 1, 2:

• Week 1: 50 mg (<50 kg), 60 mg (50-75 kg), 75 mg (>75 kg) 1
• Week 2: 25 mg (<50 kg), 30 mg (50-75 kg), 40 mg (>75 kg) 1
• Weeks 3-4: 20 mg (<50 kg), 25 mg (50-75 kg), 30 mg (>75 kg) 1
• Continue tapering to 5 mg daily by weeks 19-20, then maintain 5 mg through week 52 1, 2

Alternatively, consider initial IV methylprednisolone 500-1000 mg/day for 1-3 days before transitioning to oral prednisone 3, 4

Essential Supportive Measures

Mandatory prophylaxis and supportive care 1, 2, 5:

• Pneumocystis jirovecii prophylaxis: Trimethoprim-sulfamethoxazole 800/160 mg on alternate days or 400/80 mg daily for all patients receiving cyclophosphamide 1, 2, 5
• Antiemetic therapy: Routinely administer with intravenous cyclophosphamide 1
• Hemorrhagic cystitis prevention: High fluid intake or intravenous fluids on cyclophosphamide infusion days 1
• Osteoporosis prophylaxis: Calcium, vitamin D, and bisphosphonates 3

Adjunctive Plasma Exchange

Consider adding plasma exchange for the following scenarios 1, 2, 5:

• Serum creatinine >3.4 mg/dL (>300 μmol/L) 1, 2
• Patients requiring dialysis or with rapidly increasing serum creatinine 1, 5
• Diffuse alveolar hemorrhage with hypoxemia (if pulmonary involvement present) 1, 5

Maintenance Therapy After Remission

Transition to maintenance therapy after achieving remission (typically 3-6 months) 1, 5:

• Azathioprine: 1.5-2 mg/kg/day, preferred first-line maintenance agent 1
• Rituximab: Alternative option, particularly for relapsing disease 1, 5
• Mycophenolate mofetil: 2000 mg/day (divided doses) if azathioprine intolerant 1, 5
• Continue low-dose glucocorticoids (≤10 mg/day prednisone equivalent) 1
• Maintain therapy for 18 months to 4 years after induction of remission 1

Monitoring Strategy

Regular assessment is essential 5, 3:

• Monitor renal function, urinalysis, inflammatory markers, and ANCA levels (if positive) 5, 3
• Persistent hematuria may indicate ongoing disease activity 3
• Monitor for drug toxicity with complete blood counts and renal function tests 5, 3
• Perform repeat kidney biopsy if no improvement within 2 weeks following cessation of hematuria or if kidney function fails to improve 1

Critical Pitfalls to Avoid

Do not delay treatment while waiting for biopsy results if clinical presentation and laboratory findings are compatible with rapidly progressive glomerulonephritis 1, 2, 3

Do not use standard IgAN immunosuppression protocols (corticosteroids alone or with azathioprine) for crescentic IgAN—these patients require the more aggressive ANCA vasculitis protocol 1

Do not withhold treatment based on unfavorable histologic findings—kidney recovery can occur even with advanced damage 3

Distinguish this from IgA vasculitis (Henoch-Schönlein purpura) with nephritis, which may have additional extrarenal manifestations requiring modified treatment strategies 1, 6