Learning objectives
The reader should be able to recognize pulmonary–renal and renal-limited vasculitic syndromes, interpret PR3- and MPO-ANCA testing, distinguish AAV from anti-GBM and immune-complex GN, triage rapidly progressive kidney failure, select contemporary induction and maintenance strategies, use plasma exchange and avacopan appropriately, and monitor relapse, infection, and treatment toxicity.
Guideline currency. This chapter follows the KDIGO 2024 focused update for ANCA-associated vasculitis, including its subsequent corrigenda and the 2026 KDOQI commentary. The update incorporates reduced glucocorticoid exposure, rituximab, cyclophosphamide, avacopan, and selected plasma-exchange use.[inline_viewer url="https://kdigo.org/wp-content/uploads/2026/04/KDOQI-Commentary-KDIGO-2024-ANCA-Vasculitis-Guideline.pdf"]
18.1 Syndrome-first framing
Renal vasculitis is a clinicopathologic syndrome of vascular and glomerular inflammation. The most urgent phenotype is rapidly progressive GN with hematuria, dysmorphic RBCs or RBC casts, proteinuria, and a rapidly falling eGFR. AAV is a major cause of pauci-immune necrotizing crescentic GN, but ANCA positivity is not synonymous with vasculitis and ANCA-negative disease occurs. Infection, anti-GBM disease, lupus nephritis, IgA vasculitis, cryoglobulinemia, drug-induced vasculitis, and thrombotic microangiopathy remain important alternatives.
18.2 Classification and clinical patterns
GPA is commonly associated with PR3-ANCA and upper-airway, pulmonary, and renal disease, but not every patient has all three. MPA is often MPO-ANCA-positive and produces pulmonary capillaritis and GN without granulomatous upper-airway disease. EGPA is defined clinically by asthma, eosinophilia, and vasculitic organ involvement; renal disease is less common and may be pauci-immune or immune-complex. Renal-limited pauci-immune GN may lack systemic features.
IgA vasculitis, cryoglobulinemic vasculitis, anti-GBM disease, and lupus nephritis are not AAV, although they can produce the same RPGN phenotype and require different treatment. A positive ANCA can occur with infection, inflammatory bowel disease, autoimmune disease, medications, and malignancy; antigen-specific PR3/MPO testing is more informative than an isolated immunofluorescence pattern.
18.3 Diagnostic emergency pathway
Admit or urgently evaluate patients with rapidly rising creatinine, active sediment, pulmonary hemorrhage, hypoxemia, severe hypertension, neurologic deficits, mononeuritis multiplex, skin necrosis, or gastrointestinal ischemia. Obtain CBC, creatinine/eGFR, electrolytes, urinalysis with microscopy, ACR/PCR, CRP/ESR, PR3/MPO-ANCA, anti-GBM antibody, C3/C4, ANA/dsDNA, hepatitis and HIV tests, blood cultures when infection is plausible, and chest imaging when pulmonary disease is suspected.
Kidney biopsy is strongly useful when feasible because it confirms necrotizing/crescentic GN, estimates activity and chronicity, and identifies immune deposits or an alternative diagnosis. In a life-threatening pulmonary–renal syndrome, treatment should not be delayed solely because biopsy is pending. However, empiric immunosuppression requires urgent infection assessment and specialist involvement.
18.4 Pathology and prognosis
AAV classically shows necrotizing and crescentic lesions with pauci-immune immunofluorescence. The Berden classification—focal, crescentic, mixed, or sclerotic—provides prognostic context, while interstitial fibrosis and tubular atrophy reflect chronic damage. Anti-GBM overlap, immune-complex deposits, or prominent TMA changes alter treatment. A biopsy with advanced chronic sclerosis may show limited recovery potential even when serology is strongly positive.
18.5 Induction treatment
For organ- or life-threatening AAV, induction combines glucocorticoids with rituximab or cyclophosphamide. Reduced-dose glucocorticoid protocols are preferred when clinically appropriate because infection and metabolic toxicity materially affect outcomes. Avacopan may provide a glucocorticoid-sparing strategy in selected adults, subject to eligibility, liver monitoring, drug interactions, cost, and local approval.
Rituximab is especially useful in relapsing disease, PR3-ANCA disease, fertility-sensitive patients, and those with prior cyclophosphamide exposure. Cyclophosphamide remains important in severe renal disease, high inflammatory burden, limited rituximab access, or selected rescue settings. Dose and route must be adjusted for age, kidney function, leukopenia, infection risk, and reproductive goals.
Plasma exchange is not routine for every AAV patient. It may be considered in selected severe kidney presentations and is particularly important in anti-GBM overlap. Pulmonary hemorrhage decisions depend on severity, hypoxemia, anti-GBM status, kidney function, and bleeding risk; plasma exchange should not be presented as universally indicated.
18.6 Maintenance and relapse prevention
Maintenance commonly uses rituximab, azathioprine, or another guideline-consistent agent after remission induction. Duration is individualized, commonly at least 18 months and often longer in PR3-ANCA disease, relapsing disease, persistent ANCA positivity, or high-risk systemic disease. Monitor immunoglobulins, vaccination status, hepatitis B, infection, cytopenias, reproductive goals, and glucocorticoid toxicity. Pneumocystis prophylaxis is appropriate for many patients receiving high-dose glucocorticoids combined with rituximab or cyclophosphamide, with agent choice adjusted for eGFR and potassium.
ANCA titers may support risk assessment but should not dictate treatment in isolation. A rise in ANCA without clinical disease is not automatically a relapse. Relapse is defined clinically by new or worsening organ involvement and requires distinction from infection, drug toxicity, and chronic damage.
18.7 Supportive kidney care
Manage blood pressure, volume, hyperkalemia, acidosis, anemia, and CKD complications. Avoid nephrotoxins, adjust antimicrobial doses, and use dialysis for standard indications. Vaccinate before rituximab when possible. In dialysis-dependent presentation, reassess for recovery over time; dialysis dependence at presentation does not always imply irreversible disease, especially when biopsy shows active rather than sclerotic lesions.
Clinical pearls
- RPGN is a clinical syndrome; crescents are a lesion pattern, not a diagnosis.
- PR3/MPO antigen-specific testing is more useful than c-ANCA/p-ANCA terminology alone.
- ANCA positivity can occur without AAV, and ANCA-negative pauci-immune GN exists.
- Anti-GBM testing is urgent in pulmonary–renal disease because overlap changes treatment.
- Plasma exchange is selected therapy, not routine treatment for all AAV.
- Reduced-glucocorticoid regimens and avacopan can reduce steroid toxicity in appropriate patients.
- ANCA titers do not replace clinical assessment of relapse.
- Infection exclusion and prophylaxis are part of induction therapy, not optional add-ons.
| Syndrome | Typical pathology/serology | Management emphasis |
|---|---|---|
| AAV | Pauci-immune necrotizing/crescentic GN; PR3 or MPO may be positive | Rituximab or cyclophosphamide with reduced glucocorticoids |
| Anti-GBM disease | Linear IgG along GBM; anti-GBM antibody | Urgent plasma exchange plus immunosuppression when appropriate |
| Immune-complex GN | Granular deposits; complements or disease-specific serology | Treat underlying disease or infection; avoid reflex immunosuppression |
| AAV/anti-GBM overlap | Pauci-immune plus linear IgG features | Treat overlap urgently and individualize plasma exchange |
Summary
Renal vasculitis should be approached as an emergency syndrome with parallel serologic, infectious, imaging, and biopsy evaluation. AAV commonly causes pauci-immune necrotizing crescentic GN, but anti-GBM, immune-complex, IgA, infection-related, and drug-induced processes must be excluded. Current KDIGO guidance favors rituximab or cyclophosphamide with glucocorticoid minimization, selected avacopan use, and individualized plasma exchange. Long-term care requires relapse prevention, infection prophylaxis, vaccination, immunoglobulin monitoring, and attention to chronic kidney damage.
Question 1
A patient has hemoptysis, creatinine 5.0 mg/dL, RBC casts, and MPO-ANCA positivity. Which additional test is most urgent?
A. Anti-GBM antibody B. Anti-PLA2R antibody C. Serum IgE D. HbA1c
Answer: A. Anti-GBM overlap is time-critical and can coexist with ANCA positivity.
Question 2
Which statement about plasma exchange in AAV is most accurate?
A. It is mandatory for every patient with creatinine above 2 mg/dL. B. It is never indicated. C. It is considered selectively in severe kidney disease, pulmonary hemorrhage, or anti-GBM overlap. D. It replaces induction immunosuppression.
Answer: C. Its use is individualized and does not replace induction therapy.
Question 3
A rise in MPO-ANCA occurs during remission without new symptoms. What is the best interpretation?
A. Treat immediately as relapse. B. Ignore permanently. C. Reassess clinically and monitor; ANCA trend alone does not define relapse. D. Repeat biopsy in every case.
Answer: C. Clinical disease determines relapse treatment.
Question 4
Which induction approach is guideline-concordant for organ-threatening AAV?
A. ACE inhibitor alone B. Rituximab or cyclophosphamide plus glucocorticoid minimization C. Long-term high-dose prednisone alone D. Plasma exchange alone
Answer: B. A potent remission-induction agent is required.
Question 5
What biopsy finding suggests anti-GBM disease rather than AAV?
A. Pauci-immune staining B. Linear IgG along the GBM C. Full-house granular deposits D. Dominant C3 only
Answer: B. Linear IgG is characteristic of anti-GBM antibody binding.
Question 6
Which patient is most likely to benefit from rituximab maintenance planning?
A. A patient with high relapse risk and prior remission after rituximab B. A patient with active uncontrolled infection C. A patient with untreated anti-GBM disease and no induction D. A patient with isolated positive ANCA and no clinical disease
Answer: A. Maintenance is selected after remission and individualized by relapse risk and safety.