When is ANCA (Antineutrophil Cytoplasmic Antibody) testing recommended in patients with IgA (Immunoglobulin A) nephropathy?

ANCA Testing in IgA Nephropathy

ANCA testing should be requested in IgA nephropathy patients who present with rapidly progressive renal failure (rapidly declining GFR over days to weeks), particularly when accompanied by crescentic glomerulonephritis on biopsy, to identify concurrent ANCA-associated vasculitis that requires aggressive immunosuppression and carries a worse prognosis. 1, 2

Primary Indication: Rapidly Progressive Disease

The most critical scenario requiring ANCA testing in IgA nephropathy is rapidly declining kidney function:

• Request ANCA when serum creatinine is rapidly rising or when eGFR is declining precipitously over days to weeks, especially if eGFR falls below 15 mL/min 2, 3
• Test when there is acute kidney injury superimposed on known IgA nephropathy, as this may indicate concurrent ANCA-associated vasculitis requiring different treatment 1, 2
• The coexistence of IgA nephropathy and ANCA positivity occurs in approximately 1.2-3% of IgA nephropathy patients, making it uncommon but clinically significant 2, 3

Clinical Features Triggering ANCA Testing

Order ANCA testing when IgA nephropathy patients develop:

• Pulmonary-renal syndrome with alveolar hemorrhage or hemoptysis, which suggests concurrent AAV 4
• Systemic vasculitis symptoms including upper respiratory tract involvement (chronic sinusitis, nasal crusting, epistaxis), peripheral neuropathy (mononeuritis multiplex), or palpable purpura 5, 6
• Crescentic glomerulonephritis on kidney biopsy, as this histologic pattern may indicate superimposed ANCA-associated vasculitis 1, 7, 8
• Disproportionately severe proteinuria (typically around 1.5 g/day) combined with dysmorphic hematuria and red cell casts suggesting active glomerular inflammation 2, 3

Testing Methodology

Use high-quality antigen-specific immunoassays for both MPO-ANCA and PR3-ANCA as the primary screening method, not indirect immunofluorescence alone 4

• Both MPO and PR3 should be tested simultaneously, as approximately 90% of ANCA-associated vasculitis cases are positive for one of these antibodies 4
• In IgA nephropathy with ANCA positivity, MPO-ANCA (P-ANCA pattern) is more commonly detected than PR3-ANCA 7
• A negative ANCA does not exclude concurrent vasculitis, as about 10% of true AAV patients are persistently ANCA-negative 4

Therapeutic and Prognostic Implications

ANCA positivity in IgA nephropathy fundamentally changes management:

• Aggressive immunosuppression is required when ANCA is positive: methylprednisolone plus cyclophosphamide or rituximab, similar to ANCA-associated vasculitis protocols 1, 2
• Standard IgA nephropathy treatment (supportive care with RAS blockade and potentially corticosteroids) is insufficient for ANCA-positive cases with rapidly progressive disease 1, 2
• ANCA positivity confers worse prognosis in IgA nephropathy, with higher risk of progression to end-stage renal disease if not treated aggressively 1, 7, 8
• Plasma exchange, mycophenolate mofetil, and IVIG may be considered as alternative or adjunctive therapies 1

Key Diagnostic Pitfalls

Do not delay treatment while waiting for biopsy results if clinical presentation is compatible with small-vessel vasculitis and ANCA is positive, especially in rapidly deteriorating patients 4

Distinguish true ANCA-positive IgA nephropathy from:

• Pure ANCA-associated vasculitis with incidental IgA deposits (AAV patients have more extrarenal manifestations, older age, and less immune complex deposition) 3
• Other causes of rapidly progressive glomerulonephritis including anti-GBM disease (test for anti-GBM antibodies in pulmonary-renal syndrome) 4
• Systemic lupus erythematosus or other autoimmune diseases (check ANA, as ANCA-positive IgA nephropathy patients have higher ANA positivity rates) 3

Serial ANCA monitoring is not useful for following disease activity in ANCA-positive IgA nephropathy, as titers may remain elevated despite clinical remission 7