Opinion
Video
Diagnosing IgA Nephropathy
Panelists discuss how immunoglobulin A (IgA) nephropathy diagnosis requires kidney biopsy with immunofluorescence showing dominant or codominant IgA deposits in the mesangium, often accompanied by C3 and sometimes IgG or IgM.
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.
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