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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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