What is the role of Plasma Exchange (PLEX) in the treatment of ANCA (Anti-Neutrophil Cytoplasmic Antibodies) Vasculitis?

Role of Plasma Exchange in ANCA Vasculitis

Plasma exchange should NOT be routinely used in ANCA vasculitis, but reserve it for patients at moderate-high to high risk of end-stage kidney disease (ESKD), specifically those with serum creatinine ≥500 μmol/L or requiring dialysis. 1

Risk-Stratified Approach to Plasma Exchange

Patients with Kidney Involvement

Low to Low-Moderate Risk (Creatinine <500 μmol/L):

• Do not use plasma exchange 1
• The 2022 BMJ guideline makes a weak recommendation against PLEX in this population based on the PEXIVAS trial showing no mortality or ESKD benefit 1, 2
• Standard immunosuppression with rituximab or cyclophosphamide plus glucocorticoids is sufficient 3

Moderate-High to High Risk (Creatinine ≥500 μmol/L or dialysis-dependent):

• Consider plasma exchange as adjunctive therapy 1
• Multiple guidelines (KDIGO 2020, EULAR/ERA-EDTA 2016, BSR/BHPR 2021) support PLEX for severe renal impairment with creatinine ≥500 μmol/L 1
• ASFA 2020 provides a strong recommendation for PLEX as accepted second-line therapy in biopsy-proven rapidly progressive glomerulonephritis with creatinine ≥500 μmol/L 1
• The benefit is greatest when there is potential for renal recovery, particularly in patients who are oliguric 1

Patients with Pulmonary Hemorrhage WITHOUT Renal Involvement

Do not use plasma exchange 1

• The 2022 BMJ guideline makes a weak recommendation against PLEX for isolated pulmonary hemorrhage without kidney disease 1
• This represents a shift from older guidelines that favored PLEX for this indication 1

Patients with Pulmonary Hemorrhage WITH Severe Renal Involvement

Use plasma exchange 1

• When diffuse alveolar hemorrhage occurs with severe kidney disease (creatinine ≥500 μmol/L), PLEX is indicated 1
• KDIGO 2020 favors PLEX for AAV with diffuse alveolar hemorrhage plus hypoxemia 1
• ASFA 2020 considers PLEX a class I indication (accepted first-line therapy) for pulmonary hemorrhage with strong recommendation 1

Key Evidence: The PEXIVAS Trial

The landmark PEXIVAS trial (704 patients, up to 7 years follow-up) fundamentally changed practice patterns 2:

• No benefit on the primary composite outcome of death or ESKD (28.4% with PLEX vs 31.0% without; HR 0.86,95% CI 0.65-1.13, p=0.27) 2
• No effect on mortality or disease relapse 1, 2
• The trial included all patients with GFR <50 mL/min, not just those with severe disease, which diluted potential benefits in the highest-risk subgroup 4

Critical Nuances and Caveats

The PEXIVAS trial has important limitations:

• It enrolled patients with moderate kidney impairment (GFR <50 mL/min), not exclusively those with severe disease (creatinine ≥500 μmol/L) 4
• Lack of histological parameters makes it difficult to identify patients with potential for renal recovery 4
• There was a trend toward benefit in the alveolar hemorrhage subgroup, though not statistically significant 4

Observational data suggests potential benefit in specific scenarios:

• Patients with creatinine >300 μmol/L and rapidly deteriorating function may benefit 5
• Those who are dialysis-dependent at presentation may have improved renal recovery 5
• Patients double-positive for anti-GBM antibodies and ANCA should receive PLEX 5

Practical Implementation

When using plasma exchange:

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

Common pitfalls to avoid:

• Do not use PLEX routinely for all patients with AAV and kidney involvement 1
• Do not delay standard immunosuppression while arranging PLEX 3
• Do not use PLEX as monotherapy—it must be adjunctive to immunosuppression 1
• Do not assume PLEX prevents relapse—it has no effect on relapse rates 1, 2

Glucocorticoid Dosing Consideration

Use a reduced-dose glucocorticoid regimen (strong recommendation) 1:

• The PEXIVAS trial demonstrated that reduced-dose glucocorticoids are noninferior to standard dosing for death/ESKD outcomes 2
• Reduced dosing results in fewer serious infections (incidence rate ratio 0.69,95% CI 0.52-0.93) 2
• This applies regardless of whether PLEX is used 1