Management of ANCA Vasculitis with Renal Involvement
For ANCA vasculitis with renal involvement, initiate treatment immediately with glucocorticoids combined with either rituximab or cyclophosphamide, without waiting for kidney biopsy results if the clinical presentation and positive MPO- or PR3-ANCA serology are compatible with vasculitis. 1
Initial Treatment Decision
When to Start Treatment
- Begin immunosuppressive therapy immediately in patients with clinical presentation compatible with small-vessel vasculitis and positive ANCA serology, especially if rapidly deteriorating, even before biopsy confirmation. 1
- Patients should ideally be managed at centers with experience in AAV management. 1
Choosing Between Rituximab and Cyclophosphamide
For severe renal impairment (serum creatinine >4 mg/dL or >354 μmol/L), cyclophosphamide is preferred over rituximab. 1
Additional factors favoring cyclophosphamide: 1
- Rapidly declining GFR
- Serum creatinine >4 mg/dL (>354 μmol/L)
- Patients requiring or approaching dialysis
For less severe renal involvement (creatinine <4 mg/dL), either rituximab or cyclophosphamide can be used with similar efficacy. 1
A hybrid approach combining rituximab with 2 intravenous pulses of cyclophosphamide can be considered for severe GN. 1
Induction Therapy Regimens
Cyclophosphamide Dosing 1
Intravenous route:
- 15 mg/kg at weeks 0,2,4,7,10,13 (with additional doses at weeks 16,19,21,24 if needed)
- Reduce dose by 2.5 mg/kg for age >60 years (12.5 mg/kg) and >70 years (10 mg/kg)
- Reduce dose by 2.5 mg/kg if GFR <30 ml/min/1.73 m²
Oral route:
- 2 mg/kg/day for 3 months, continue for ongoing activity to maximum of 6 months
- Reduce to 1.5 mg/kg/day for age >60 years and 1.0 mg/kg/day for age >70 years
- Reduce by 0.5 mg/kg/day if GFR <30 ml/min/1.73 m²
Rituximab Dosing 1, 2
Two dosing options:
- 375 mg/m²/week × 4 weeks, OR
- 1 g at weeks 0 and 2
For severe renal disease, limited data support rituximab monotherapy with glucocorticoids; consider adding cyclophosphamide pulses. 1
Glucocorticoid Protocol 1
Initial dosing:
- Intravenous methylprednisolone: 1-3 g total (often given as 500-1000 mg/day for 1-3 days) for severe presentations
- Oral prednisolone: 1 mg/kg/day (maximum 60-80 mg/day) for the first week
Tapering schedule:
- Target dose of 10 mg by approximately 19 weeks
- Target dose of 7.5 mg by approximately 21 weeks
- Reduce to 5 mg/day by 6 months 1
- Following rituximab induction, prednisolone can be withdrawn by 6 months 1
Adjunctive Therapies
Plasma Exchange Considerations
Consider plasma exchange for: 1
- Serum creatinine >3.4 mg/dL (>300 μmol/L)
- Patients requiring dialysis or with rapidly increasing creatinine
- Diffuse alveolar hemorrhage with hypoxemia
The evidence is mixed: the MEPEX trial showed benefit for severe renal disease (creatinine >5.7 mg/dL), but the PEXIVAS trial failed to demonstrate delayed time to kidney failure or death. Meta-analyses confirm reduction in kidney failure risk at 12 months but with increased serious infection risk. 1
For serum creatinine >5.7 mg/dL (>500 μmol/L), plasma exchange should be considered despite mixed evidence. 1
Prophylaxis 1
- Pneumocystis jirovecii pneumonia prophylaxis: Trimethoprim-sulfamethoxazole for all patients receiving cyclophosphamide or rituximab
- Osteoporosis prophylaxis: Calcium, vitamin D, and bisphosphonates given high-dose glucocorticoid exposure
Maintenance Therapy
After achieving remission (typically 3-6 months), transition to maintenance therapy with low-dose glucocorticoids plus one of the following: 1
Maintenance Options (in order of preference for relapsing disease):
- Rituximab: Can be dosed on fixed schedule (biannually) or upon reappearance of CD19+ B cells and/or ANCA 1
- Azathioprine: 2 mg/kg/day, equally effective as extended cyclophosphamide with less leukopenia 1
- Methotrexate 1
- Mycophenolate mofetil: 2000-3000 mg/day 1
Rituximab is preferred over cyclophosphamide for relapsing disease due to lower cumulative toxicity. 1
Monitoring Strategy
Disease Activity Monitoring 1
- Regular assessment of renal function and urinalysis
- Inflammatory markers (CRP, ESR)
- ANCA levels: Persistence, increase, or conversion from negative to positive may predict relapse and should guide treatment decisions
Drug Toxicity Monitoring 1
- Complete blood counts regularly (especially with cyclophosphamide)
- Renal function tests
- Monitor for infections given immunosuppression
B Cell Monitoring (for rituximab-treated patients) 3
- All relapses in rituximab-treated patients occur after B cell return
- Consider B cell monitoring to guide maintenance rituximab dosing
Critical Pitfalls to Avoid
Do not delay treatment while waiting for biopsy results in patients with compatible clinical presentation and positive PR3- or MPO-ANCA serology, especially if rapidly deteriorating. 1
Do not use rituximab monotherapy for severe renal impairment (creatinine >4 mg/dL) without considering cyclophosphamide or combination therapy, as data supporting rituximab in this setting are limited. 1
Do not underestimate glucocorticoid toxicity: Follow structured tapering protocols and avoid prolonged high doses beyond evidence-based regimens. 1
Do not withhold treatment based solely on unfavorable histologic findings, as kidney recovery can occur even with advanced damage. 1
Do not forget prophylaxis: PCP prophylaxis is essential and osteoporosis prophylaxis should be implemented early. 1