What is the name of the histological classification of membranous nephropathy?

Histological Classification of Membranous Nephropathy

The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification is the standard histological classification system for membranous nephropathy, characterized primarily by subepithelial immune complex deposits. 1

Key Histological Features

Primary Diagnostic Finding

• Subepithelial immune deposits: The pathognomonic finding of membranous nephropathy
  • Located between podocytes and the glomerular basement membrane
  • Appear as granular, electron-dense, unorganized structures on electron microscopy 2
  • Often contain antibodies against phospholipase A2 receptor (PLA2R) in primary membranous nephropathy 2

Stages of Membranous Nephropathy (Ehrenreich-Churg Classification)

The histological staging is based on the location and appearance of immune deposits and basement membrane changes:

1. Stage I: Subepithelial deposits without GBM thickening
2. Stage II: Deposits with projections of basement membrane material between deposits
3. Stage III: Deposits completely surrounded by basement membrane material
4. Stage IV: Deposits with incorporation into thickened, irregular basement membrane with lucent areas 3

Immunofluorescence Findings

• Granular capillary wall deposits of IgG (predominant)
• Often with C3 complement deposition
• May have kappa and lambda light chains with similar intensity 1

Clinical-Pathological Correlations

Prognostic Significance

• Higher histological stages (III-IV) are associated with increased risk of progression to end-stage renal failure (hazard ratio 5.3) 3
• The presence of tubulointerstitial lesions, vascular sclerosis, and secondary focal segmental glomerulosclerosis correlates with poorer renal outcomes 4
• However, these histologic features are not independent predictors of outcome when controlling for baseline clinical variables (age, blood pressure, creatinine clearance) 4

Membranous Nephropathy in Lupus Nephritis

• Classified as Class V in the ISN/RPS classification for lupus nephritis 1
• When combined with proliferative lesions (Class III or IV), should be treated as Class III or IV 1
• Pure membranous lupus nephropathy (Class V alone) may be approached differently from proliferative forms 1, 5

Differential Diagnosis Based on Histology

• Immune-complex GN: Different pattern of deposits (mesangial, subendothelial) 1
• Proliferative GN: Shows diffuse endocapillary proliferation not typical of membranous nephropathy 2
• IgA nephropathy: Characterized by mesangial IgA deposits rather than subepithelial deposits 2
• C3 glomerulopathy: Dominant C3 with minimal or no immunoglobulin deposits 1
• Monoclonal gammopathy-associated membranous pattern: May show restriction to a single light chain type 1

Clinical Implications of Histological Classification

• Histological classification guides therapeutic decisions:

  • Class V membranous nephropathy with nephrotic-range proteinuria (>3.5g/day) warrants immunosuppressive therapy 1
  • Non-nephrotic proteinuria may be managed with conservative therapy including RAS blockade 6, 7
  • The presence of proliferative features requires more aggressive immunosuppression 1

• The extent and characteristics of deposits may correlate with treatment response and long-term prognosis 2

The ISN/RPS classification system provides a standardized approach to the histological evaluation of membranous nephropathy, facilitating appropriate treatment decisions and prognostication based on morphological features.