2024 KDIGO Guideline Update — Plasma Exchange Indications Refined
The KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis provides the most authoritative update on PLEX indications since the PEXIVAS trial. The key message: routine PLEX is no longer recommended for most AAV patients. Plasma exchange remains indicated in specific high-risk clinical scenarios. This page reflects the current 2024 KDIGO standard.
Clinical Overview
ANCA-associated vasculitis (AAV) is a group of necrotizing small-vessel vasculitides characterized by the presence of anti-neutrophil cytoplasmic antibodies (ANCA) targeting proteinase-3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The two major forms are granulomatosis with polyangiitis (GPA, formerly Wegener's) and microscopic polyangiitis (MPA). Both can cause rapidly progressive glomerulonephritis (RPGN), pulmonary hemorrhage, and multi-organ failure.
The biological rationale for plasma exchange in AAV is the removal of circulating ANCA, which are believed to activate neutrophils and cause endothelial injury. However, the relationship between ANCA titers and disease activity is imperfect, and the clinical benefit of ANCA removal via TPE has been substantially revised by large randomized trial data.
KDIGO 2024 Guideline: When to Use (and Not Use) Plasma Exchange
PLEX IS Recommended
- Dialysis-dependent at presentation — PLEX may improve renal recovery in patients requiring dialysis at diagnosis
- AAV + anti-GBM overlap syndrome — Concurrent anti-GBM antibodies require urgent PLEX to remove both ANCA and anti-GBM antibodies
- Severe diffuse alveolar hemorrhage (DAH) with hypoxemia — Consider PLEX in life-threatening pulmonary hemorrhage with respiratory failure
PLEX is NOT Recommended
- Routine use for all AAV with RPGN — Not indicated for patients with GFR <50 mL/min/1.73m² who are not dialysis-dependent
- Alveolar hemorrhage without hypoxemia — Radiographic DAH alone without respiratory compromise does not warrant PLEX
- Elevated ANCA titers alone — Titer elevation without severe organ involvement is not an indication
- Maintenance or relapse prevention — No evidence supports PLEX for relapse prevention
KDIGO 2024 Key Recommendation (Kidney International, 2024)
"We suggest not routinely adding plasma exchange to standard immunosuppressive therapy for patients with ANCA-associated GN who do not require dialysis at presentation (2B). We suggest considering plasma exchange for patients with ANCA-associated GN who require dialysis at presentation (2C), and for patients with concurrent anti-GBM antibodies (1B)."
The PEXIVAS Trial and Its Implications
PEXIVAS: Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis
| Parameter | Detail |
|---|---|
| Citation | Walsh M, et al. N Engl J Med. 2020;382(7):622–631. doi:10.1056/NEJMoa1803537 |
| Population | Adults with severe AAV (eGFR <50 or alveolar hemorrhage) — GPA and MPA |
| Intervention | 7 sessions of TPE (60 mL/kg, max 4L, albumin/FFP replacement) vs. no PLEX |
| Primary Endpoint | Composite of death or end-stage kidney disease (ESKD) at 2 years |
| Primary Result | No significant difference: PLEX 28.4% vs. no PLEX 31.0% (HR 0.86, 95% CI 0.65–1.13, p=0.27) |
| Conclusion | PLEX did not reduce the risk of death or ESKD in severe AAV at 2 years |
PEXIVAS Secondary Analysis — Odler et al. (Kidney International, 2025)
A 2025 secondary analysis of the PEXIVAS trial by Odler et al. examined early renal function outcomes, adding important nuance to the primary negative result.
| Parameter | Detail |
|---|---|
| Citation | Odler B, et al. Kidney Int. 2025;107(3):558–567. doi:10.1016/j.kint.2024.11.029 |
| Key Finding | PLEX significantly improved early kidney function (eGFR) within the first 12 months compared to no PLEX, even though long-term ESKD rates were not different |
| Clinical Implication | PLEX may provide a meaningful short-term renal benefit in dialysis-dependent patients, potentially enabling renal recovery even if long-term ESKD rates are unchanged |
| Subgroup of Interest | Patients with dialysis-dependent AAV at presentation showed the most benefit from PLEX in early renal function recovery |
Reconciling PEXIVAS and KDIGO 2024: PEXIVAS showed no long-term survival or ESKD benefit from routine PLEX in all severe AAV. However, the 2025 secondary analysis shows early renal recovery benefit in dialysis-dependent patients. KDIGO 2024 synthesizes this by recommending against routine PLEX but retaining it as an option for dialysis-dependent patients and anti-GBM overlap — where the short-term benefit of renal recovery is most clinically meaningful.
Procedure Protocol (When Indicated)
| Parameter | Recommendation |
|---|---|
| Number of sessions | 7 sessions over 14 days (PEXIVAS protocol); some centers use up to 9 sessions |
| Volume per session | 60 mL/kg body weight, maximum 4 liters per session |
| Replacement fluid | 5% albumin for most sessions; FFP for last 1–2 sessions if coagulopathy present or surgical procedure planned |
| Anticoagulation | Citrate preferred; heparin if citrate not available and no contraindications |
| Concurrent therapy | Cyclophosphamide or rituximab + glucocorticoids (per KDIGO 2024 induction protocol) |
| Monitoring | ANCA titers, creatinine, urinalysis, CBC, coagulation studies before each session |
| Duration of benefit | Short-term renal recovery; does not replace immunosuppression for long-term remission |
Special Case: AAV + Anti-GBM Overlap Syndrome
Approximately 5–10% of patients with anti-GBM disease have concurrent ANCA positivity (most commonly MPO-ANCA). This overlap syndrome carries a particularly poor prognosis. In this setting, urgent plasma exchange is strongly recommended (ASFA Category I, Grade 1B) to rapidly remove both ANCA and anti-GBM antibodies simultaneously.
Protocol: Daily TPE with FFP replacement (to replenish clotting factors), typically 14 sessions over 2–3 weeks, combined with cyclophosphamide and high-dose corticosteroids. Renal outcomes are better when treatment is initiated before dialysis dependence.
ASFA Classification Summary
| Clinical Scenario | ASFA Category | Grade | 2024 KDIGO Alignment |
|---|---|---|---|
| AAV with dialysis-dependent RPGN | Cat I | 1B | Suggested (2C) |
| AAV + anti-GBM overlap syndrome | Cat I | 1B | Recommended (1B) |
| Severe DAH with hypoxemia | Cat I | 1C | Consider (expert opinion) |
| AAV with RPGN, not dialysis-dependent | Cat II | 2B | Not recommended routinely (2B) |
| DAH without hypoxemia | Cat III | 2C | Not recommended |
References
All references verified February 2026. DOIs and PubMed IDs confirmed against publisher records. Links open in a new tab.
- 1. Floege J, Jayne DRW, Sanders JF, Tesar V, Balk EM, Gordon CE, et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis. Kidney Int. 2024;105(3):447–449. doi:10.1016/j.kint.2023.10.009 — PubMed 38388147 Open Access
- 2. Walsh M, Merkel PA, Peh CA, Szpirt WM, Puéchal X, Fujimoto S, et al.; PEXIVAS Investigators. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020;382(7):622–631. doi:10.1056/NEJMoa1803537 — PubMed 32053298 Free PMC Article
- 3. Odler B, Riedl R, Geetha D, Szpirt WM, Hawley C, Uchida L, et al.; PEXIVAS Investigators. The effects of plasma exchange and glucocorticoids on early kidney function among patients with ANCA-associated vasculitis in the PEXIVAS trial. Kidney Int. 2025 Mar;107(3):558–567. doi:10.1016/j.kint.2024.11.029 Open Access (DOI corrected from original .09.016)
- 4. Connelly-Smith L, Alquist CR, Aqui NA, Hofmann JC, Klingel R, Onwuemene OA, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice — Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue. J Clin Apher. 2023;38(2):77–278. doi:10.1002/jca.22043 Free Full Text — PubMed 37017433
- 5. Jayne DRW, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, et al.; European Vasculitis Study Group. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007;18(7):2180–2188. doi:10.1681/ASN.2007010090 — PubMed 17582159 Free PMC Article
- 6. Lu W, Costa V, Wu DW, Alsammak M, Banez-Sese G, Chhibber V, et al. An Annual Review of Important Apheresis Articles in 2024 From the American Society for Apheresis Attending Physician Subcommittee. J Clin Apher. 2025;40(6):e70067. doi:10.1002/jca.70067 Abstract Only — PubMed 41157887
Disclaimer: This information is for educational purposes only. Clinical decisions require individualized assessment by qualified medical professionals. KDIGO guidelines represent expert consensus and should be interpreted in the context of individual patient circumstances.