ANCA-associated GN

Vittawin Sawangduan, MD

Renal Division
Department of Internal Medicine
Lampang Hospital

31/8/2022
Outline
• 2012 International Chapel Hill Consensus Conference
• Rapidly progressive glomerulonephritis
• ANCA-associated glomerulonephritis
• Pathogenesis
• Clinical presentations
• Diagnosis
• Management
Outline
• 2012 International Chapel Hill Consensus Conference
• Rapidly progressive glomerulonephritis
• ANCA-associated glomerulonephritis
• Pathogenesis
• Clinical presentations
• Diagnosis
• Management
 2012 International Chapel Hill Consensus
Conference
Small-vessel vasculitis (SVV)
• Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV)
• Microscopic polyangiitis (MPA)
• Granulomatosis with polyangiitis (Wegener) (GPA)
• Eosinophilic granulomatosis with polyangiitis (Churg- Strauss) (EGPA)
• Immune complex SVV
• Anti–glomerular basement membrane (anti-GBM) disease
• Cryoglobulinemic vasculitis (CV)
• Immunoglobulin A (IgA) vasculitis (Henoch-Sch€onlein) (IgAV)
• Hypocomplementemic urticarial vasculitis (HUV) (anti-C1q vasculitis)
2012 International Chapel Hill Consensus
Conference
Medium-vessel vasculitis (MVV)
• Polyarteritis nodosa (PAN)
• Kawasaki disease (KD)
Large-vessel vasculitis
• Takayasu arteritis (TA)
• Giant cell arteritis (GCA)
Variable vessel vasculitis (VVV)
• Behçet disease (BD)
• Cogan syndrome (CS)
Nat Rev Dis Primers 6, 71 (2020)
CHCC 2012 Definition
Microscopic polyangiitis (MPA)
• Necrotizing vasculitis, with few or no immune deposits,
predominantly affecting small vessels (i.e., capillaries, venules, or
arterioles).
• Necrotizing arteritis involving small and medium arteries may be
present.
• Necrotizing GN is very common.
• Pulmonary capillaritis often occurs.
• Granulomatous inflammation is absent.
CHCC 2012 Definition
Granulomatosis with polyangiitis (GPA) (Wegener)
• Necrotizing granulomatous inflammation usually involving the upper
and lower respiratory tract, and necrotizing vasculitis affecting
predominantly small-to-medium vessels (e.g., capillaries, venules,
arterioles, arteries, and veins).
• Necrotizing GN is common.
CHCC 2012 Definition
Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss)
• Eosinophil-rich and necrotizing granulomatous inflammation often
involving the respiratory tract, and necrotizing vasculitis
predominantly affecting small to-medium vessels, and associated
with asthma and eosinophilia.
• ANCA is more frequent when GN is present.
Outline
• 2012 International Chapel Hill Consensus Conference
• Rapidly progressive glomerulonephritis
• ANCA-associated glomerulonephritis
• Pathogenesis
• Clinical presentations
• Diagnosis
• Management
Rapidly Progressive Glomerulonephritis (RPGN)
• Rapid loss of renal function over a very short period (days to weeks)

• Nephritic urine analysis: proteinuria, micro or macroscopic

hematuria, dysmorphic red blood cells (RBC), RBC casts

• Histopathological characteristic on renal biopsy finding; crescent

formation > 50% of the obtained glomeruli
Cellular crescents
Fibrocellular crescents
Fibrous crescents
Types of RPGN
• RPGN is broadly classified based on the histopathology, immune
complex deposition and serologic tests
Type Category IF & serology Primary renal Systemic diseases
diseases
I Anti-GBM- • Glomerular linear • Anti-GBM- • Goodpasture
mediated IgG staining associated GN syndrome
• Circulating • Post KT in Alport
anti-GBM Ab syndrome
II Immune • Granular immune • PSGN • Lupus nephritis
complex- deposit • IgA nephropathy • HSP
mediated • Circulating Ab • MGPN type I&II • Cryoglobulinemia
III ANCA- • No glomerular • ANCA-associated • MPA
associated deposit GN • GPA
• Circulating ANCA • EGPA
IV Mixed Variable • Anti-GBM + ANCA
• SLE + ANCA
V Idiopathic • No glomerular • Idiopathic • ANCA-negative
deposit crescentic GN small vessel
• Serologic tests -ve vasculitis
Linear GBM staining with IgG Absence of Ig deposition
Adv Anat Pathol. 2012 Mar;19(2):111-24
Crescentic LN

CEN Case Rep 4, 126–130 (2015).

Outline
• 2012 International Chapel Hill Consensus Conference
• Rapidly progressive glomerulonephritis
• ANCA-associated glomerulonephritis
• Pathogenesis
• Clinical presentations
• Diagnosis
• Management
Pathogenesis

Clin J Am Soc Nephrol 12: 1680–1691, 2017.

Diagnostic testing methods in AAVs
• Indirect immunofluorescence (IIF)
• Antigen-specific immunoassays : most commonly enzyme-linked
immunosorbent assays (ELISAs) for PR3-ANCA or MPO-ANCA

Nat Rev Dis Primers 6, 71 (2020)

Frequency of ANCA Positivity in Different Conditions

Am J Kidney Dis. 75(1):124-137.

Nat Rev Dis Primers 6, 71 (2020)
Comparison of Clinical Features by ANCA Specificity

Am J Kidney Dis. 75(1):124-137.

Outcome
• Patient survival 70-90%
• Risk to ESKD 20-30%
Outline
• 2012 International Chapel Hill Consensus Conference
• Rapidly progressive glomerulonephritis
• ANCA-associated glomerulonephritis
• Pathogenesis
• Clinical presentations
• Diagnosis
• Management
 KDIGO 2021 Clinical Practice Guideline
for the Management of Glomerular Diseases
Diagnosis
Practice Point:
• In the case of a clinical presentation compatible with small-vessel
vasculitis in combination with positive myeloperoxidase (MPO)- or
proteinase 3 (PR3)-ANCA serology, waiting for a kidney biopsy to be
performed or reported should not delay starting immunosuppressive
therapy, especially in patients who are rapidly deteriorating
Treatment: Induction
• We recommend that glucocorticoids in combination with
cyclophosphamide or rituximab be used as initial treatment of new-
onset AAV (1B).
Treatment: Induction
• In patients presenting with markedly reduced or rapidly declining GFR
(SCr >4 mg/dl), there are limited data to support rituximab and
glucocorticoids. Cyclophosphamide and glucocorticoids are preferred
for induction therapy.

• The combination of rituximab and cyclophosphamide can also be

considered in this setting.

• Discontinue immunosuppressive therapy after 3 months in patients

who remain on dialysis and who do not have any extrarenal
manifestations of disease.
Recommendations for immunosuppressive dosing
Plasmapharesis
• Consider plasma exchange for patients with SCr > 5.7 mg/dl requiring
dialysis or with rapidly increasing SCr, and in patients with diffuse
alveolar hemorrhage who have hypoxemia.

• Add plasma exchange for patients with an overlap syndrome of ANCA

vasculitis and anti-GBM.
Maintenance therapy
• We recommend maintenance therapy with either rituximab or
azathioprine and low dose glucocorticoids after induction of remission (1C)

• The optimal duration of azathioprine plus low-dose glucocorticoids is not

known but should be between 18 months and 4 years after induction of
remission

• The optimal duration of rituximab maintenance is not known, but studies

to date have evaluated a duration of 18 months after remission
Conclusion
• ANCA-associated vasculitis : one of the small vessel vasculitis
• Usually occurs in old age
• Clinical presentation: constitutional symptoms, pulmonary
hemorrhage, RPGN, pulmonary-renal syndrome, etc
• RPGN : edema, high blood pressure, azotemia, active urine
sediments, crescentic GN
• Diagnosis : serologic test (Anti-MPO, Anti-PR3) and kidney biopsy
[normal complement level]
• Treatment: Induction and maintenance with IS, PLEX