Diagnosing IgA Nephropathy

EP: 1.Advancing IgA Nephropathy Care: Emerging Therapies, Unmet Needs, and Economic Considerations

EP: 2.Introduction to IgA Nephropathy

EP: 3.Pathogenesis of IgA Nephropathy: The 4-Hit Cascade, A Proliferation-Inducing Ligand (APRIL), and cytokines

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EP: 4.Diagnosing IgA Nephropathy

IgA Nephropathy: Diagnostic Pathology and Prognostic Features

Pathological Diagnosis

IgA nephropathy (IgAN) is definitively diagnosed through renal biopsy with the following characteristic findings:

• Light microscopy: Variable glomerular changes ranging from minimal alterations to diffuse proliferative or crescentic glomerulonephritis. Mesangial hypercellularity and matrix expansion are common findings.
• Immunofluorescence: The pathognomonic feature is predominant or codominant IgA deposits in the mesangium. These deposits are typically granular and may be accompanied by C3, IgG, and/or IgM.
• Electron microscopy: Electron-dense deposits in the mesangial regions and occasionally in subendothelial or subepithelial locations of the glomerular basement membrane.

Histopathological Predictors of Disease Progression

Oxford Classification (MEST-C Score)

The validated Oxford Classification identifies five independent histological variables that predict renal outcomes:

• M: Mesangial hypercellularity (> 50% of glomeruli)
• E: Endocapillary hypercellularity (present/absent)
• S: Segmental glomerulosclerosis (present/absent)
• T: Tubular atrophy/interstitial fibrosis (T0: ≤ 25%, T1: 26%-50%, T2: > 50%)
• C: Cellular/fibrocellular crescents (C0: none, C1: < 25%, C2: ≥ 25%)

Other Prognostic Histological Features

• Extent of glomerulosclerosis: Higher percentage of globally sclerotic glomeruli correlates with poorer outcomes
• Vascular lesions: Arteriosclerosis and arteriolosclerosis indicate worse prognosis
• Interstitial inflammation: Greater inflammation associates with more rapid progression
• Pattern of IgA deposition: Mesangial-capillary wall deposits may predict more aggressive disease than purely mesangial deposits

Histopathological Predictors of Treatment Response

• E-lesions: Patients with endocapillary proliferation often respond better to immunosuppressive therapy, particularly corticosteroids
• C-lesions: Presence of crescents (especially C2) indicates active disease that may respond to aggressive immunosuppression
• T-lesions: Advanced tubular atrophy/interstitial fibrosis (T1-T2) typically predicts poor response to immunotherapy
• Complement activation: Cases with C3 codeposition may have differential response to complement-targeting therapies
• IgG codeposition: May identify patients with more immune-active disease who could benefit from immunosuppression

Renal biopsy findings should be integrated with clinical parameters (proteinuria, GFR, hypertension) for optimal risk stratification and treatment decision-making in IgAN management.