| Disease | Endothelium | GBM | Podocytes (Epithelium) | Mesangium | Bowman’s Capsule |
|---|---|---|---|---|---|
| Minimal Change Disease | - | - | Effacement of foot processes | - | - |
| Focal Segmental Glomerulosclerosis (FSGS) | - | Hyalinosis | Effacement of foot processes | Sclerosis (collagen deposition) in segments | - |
| Membranous Nephropathy | - | Thickened; Subepithelial “spike & dome” deposits | Effacement over deposits | - | - |
| Diabetic Nephropathy | - | Thickened (non-enzymatic glycosylation) | Injury/Loss | Expansion; Kimmelstiel-Wilson nodules (eosinophilic sclerosis) | - |
| Amyloidosis | - | - | - | Apple-green birefringence (Congo red stain) deposits | - |
| PSGN (Post-Strep) | - | Subepithelial “humps” (immune complex) | - | Proliferation | - |
| IgA Nephropathy (Berger) | - | - | - | IgA deposits; Proliferation | - |
| DPGN (Lupus) | Subendothelial “wire loop” deposits | Thickened | - | Proliferation | - |
| MPGN Type I | Subendothelial deposits | ”Tram-track” appearance (splitting) | - | Proliferation; Interposition into GBM | - |
| MPGN Type II (Dense Deposit) | - | Intramembranous dense deposits | - | Proliferation | - |
| Alport Syndrome | - | Thinning & Splitting (“Basket-weave”) | - | - | - |
| RPGN (Crescentic) | - | Breaks/Rupture | - | - | Crescents (Fibrin, macrophages, parietal cells) |
Immune mechanisms of glomerular injury
- Immune complex formation within the glomerulus
- Intrinsic (fixed) glomerular antigens
- Type IV collagen: anti-GBM disease (GN)
- PLA2R: membranous nephropathy (NS)
- Deposited (“planted”) glomerular antigens
- Bacterial antigens: poststreptococcal GN
- Tumor antigens: membranous nephropathy (NS)
- Intrinsic (fixed) glomerular antigens
- Preformed immune complex deposition from the circulation
- Endogenous antigens
- Galactose-deficient IgA: IgA nephropathy (GN)
- dsDNA: lupus nephritis (GN, sometimes NS)
- Exogenous antigens
- Viral hepatitis C or B, HIV: immune complex MPGN
- Bacterial antigens: endocarditis-associated GN
- Endogenous antigens
- Neutrophil activation: minimal (pauci-) immune complex deposition
- Neutrophil cytoplasmic antigens
- MPO/PR3 (ANCA-associated GN)
- Neutrophil cytoplasmic antigens
Clinical picture determined by site of glomerular immune injury:
- NS (nephrotic syndrome): Injury to podocytes → isolated from inflammatory mediators in Bowman space/urinary side of GBM → proteinuria without inflammation
- GN (glomerulonephritis): Injury to GBM, mesangial cells, or endothelial cells (either immune- or neutrophil-mediated) → exposed to inflammatory mediators/circulatory side of GBM → glomerular hematuria & red blood cell casts; variable proteinuria