In adult ANCA‑associated vasculitis with severe renal impairment (eGFR <15 mL/min/1.73 m²) or life‑threatening pulmonary hemorrhage, should plasma exchange be used routinely?

Plasma Exchange in Severe ANCA-Associated Vasculitis

Plasma exchange should NOT be used routinely in adult ANCA-associated vasculitis with severe renal impairment (eGFR <15 mL/min/1.73 m²) or life-threatening pulmonary hemorrhage, based on the landmark PEXIVAS trial showing no reduction in death or end-stage kidney disease, but rather an increased risk of serious infections. 1

Evidence-Based Recommendation Against Routine Use

The 2022 BMJ guideline, incorporating the PEXIVAS trial (the largest and most recent high-quality evidence with 704 patients), makes a weak recommendation against routine plasma exchange for patients with severe AAV. 1 The trial demonstrated:

• No mortality benefit at 1 year: Risk difference of 1.5% reduction (95% CI: 7.1% reduction to 6.4% increase), with very low certainty evidence 1
• Increased serious infections: Risk difference of 6.8% increase (95% CI: 0.8% to 14% increase) at 1 year 1
• No reduction in ESKD or death composite: 28.4% with plasma exchange versus 31.0% without (HR 0.86,95% CI 0.65-1.13) 1

The KDIGO 2020 guideline explicitly recommends against routine use of plasma exchange for patients with GFR <50 mL/min/1.73 m². 1

When to Consider Selective Use

Despite the recommendation against routine use, plasma exchange may be considered in highly selected circumstances:

Severe Renal Disease

• Serum creatinine >500 μmol/L (5.7 mg/dL) with rapidly progressive glomerulonephritis, particularly if oliguric 1, 2
• Dialysis-dependent patients at presentation 1
• EULAR/ERA-EDTA 2016 supports consideration in this specific subset (Level 1B evidence, Grade B recommendation) 1

Life-Threatening Pulmonary Hemorrhage

• Diffuse alveolar hemorrhage WITH hypoxemia 1, 2, 3
• KDIGO 2020 favors plasma exchange specifically when hypoxemia is present 1, 2
• Important caveat: The 2022 BMJ guideline makes a weak recommendation AGAINST plasma exchange for isolated pulmonary hemorrhage without kidney disease, given increased infection risk without clear mortality benefit 2, 3

Dual Antibody-Positive Disease

• Patients positive for both ANCA and anti-GBM antibodies, especially with linear IgG staining on kidney biopsy 1

Clinical Decision Algorithm

For patients with eGFR <15 mL/min/1.73 m²:

1. Do NOT use plasma exchange routinely 1
2. Consider plasma exchange only if:
   • Serum creatinine >500 μmol/L (5.7 mg/dL) AND rapidly deteriorating function 1, 2
   • OR dialysis-dependent at presentation 1
   • OR dual ANCA/anti-GBM antibody positive 1

For life-threatening pulmonary hemorrhage:

1. Initiate high-dose IV methylprednisolone (500-1000 mg/day × 3 days) plus rituximab or cyclophosphamide immediately 3
2. Consider plasma exchange only if:
   • Hypoxemia is present (not isolated hemorrhage) 1, 2, 3
   • AND serum creatinine >300 μmol/L with rapidly deteriorating function 2
3. Weigh against 6.8% absolute increase in serious infections 1

Implementation Details (If Plasma Exchange Selected)

When plasma exchange is deemed appropriate after careful risk-benefit assessment:

• Perform 7 exchanges within 14 days of initiation 2
• Exchange volume: 1-1.5 plasma volumes (40-60 mL/kg or 3.5-4 L fixed volume) 1, 2
• Replacement fluid: Albumin and/or crystalloid 1, 2
• Method: Centrifugation or filter separation 1, 2
• Always combine with standard immunosuppression (rituximab or cyclophosphamide) plus glucocorticoids 2

Critical Glucocorticoid Dosing Recommendation

Use a reduced-dose glucocorticoid regimen (strong recommendation) based on PEXIVAS demonstrating non-inferiority for death/ESKD outcomes with significantly fewer serious infections (incidence rate ratio 0.69,95% CI 0.52-0.93). 1, 2 The reduced regimen achieves 7.5 mg prednisolone four weeks earlier than standard dosing (17 weeks versus 21 weeks). 1

Common Pitfalls to Avoid

• Do not reflexively add plasma exchange for all patients with severe renal impairment or pulmonary hemorrhage—the evidence does not support routine use 1
• Do not use plasma exchange for isolated pulmonary hemorrhage without kidney involvement—harm likely exceeds benefit 2, 3
• Do not use standard-dose glucocorticoids—the reduced regimen is equally effective with better safety 1, 2
• Do not delay immunosuppression while arranging plasma exchange—rituximab or cyclophosphamide should start immediately 3

Divergent Evidence Acknowledgment

There is tension between older guidelines (EULAR/ERA-EDTA 2016, BSR/BHPR 2021) that favor plasma exchange for severe renal disease 1 and the most recent 2022 BMJ guideline informed by PEXIVAS that recommends against routine use. 1 The key distinction is "routine" versus "selective" use—even the 2022 guideline acknowledges plasma exchange may be considered for the most severe presentations (creatinine >500 μmol/L, dialysis-dependent), but emphasizes this should be the exception rather than the rule. 1, 2