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10 marksDrNB 2025NephrologyExperimental Nephrology
a) Heymann nephritis. [3] b) Experimental model for minimal change disease. [3] c) Experimental model for Diabetic kidney disease. [4]
- Heymann nephritis is a rat model of membranous nephropathy with subepithelial immune complex deposition against megalin (Brenner & Rector’s)
- Puromycin aminonucleoside induces podocyte injury mimicking MCD – hallmark is foot process effacement without immune deposits
- Streptozotocin model induces insulin-deficient diabetes; recapitulates morphological and functional features of diabetic nephropathy
- Use of these models helps in understanding pathogenesis and evaluating therapeutic agents
- Complement activation critical in Heymann nephritis; podocyte cytoskeleton injury is central in MCD; hyperglycemia-driven metabolic and hemodynamic factors drive DKD progression
Mnemonic for models:
"HPS"
H - Heymann nephritis (Membranous)
P - Puromycin aminonucleoside (MCD)
S - Streptozotocin (Diabetic kidney disease)
References:
- Brenner & Rector's The Kidney, 11th edition, Ch. 23, 45, 58
- Harrison's Principles of Internal Medicine, 21st edition, Ch. 265
Definition
Heymann nephritis is an experimental rat model of membranous nephropathy characterized by subepithelial immune complex deposition along the glomerular basement membrane, leading to nephrotic syndrome (Brenner & Rector’s The Kidney, 11th edition, Ch. 23).
Etiopathogenesis
- Induced by immunization with renal tubular brush border antigen, mainly megalin, resulting in formation of circulating antibodies.
- These antibodies deposit subepithelially forming granular immune complexes that activate complement (C5b-9), causing podocyte injury and proteinuria.
- It mimics human idiopathic membranous nephropathy immunopathology.
| Pathogenic Mechanism | Description |
|---|---|
| Antigen | Megalin (brush border protein) |
| Antibody | IgG against megalin |
| Immune deposit location | Subepithelial |
| Complement activation | C5b-9 membrane attack complex |
| Result | Podocyte injury and proteinuria |
Clinical Features
- Proteinuria (nephrotic range)
- Edema
- No hematuria or hypertension initially (experimental model—features replicate human disease)
Diagnosis
- Demonstrated by kidney biopsy: granular IgG deposition along GBM on immunofluorescence
- Electron microscopy shows subepithelial deposits
- Serum anti-megalin antibodies detection (experimental)
Management
- Model used to study pathogenesis and test immunosuppressants (no direct human therapy)
- Used to investigate complement blockade and immunomodulation
Recent Advances
- Identification of target epitopes on megalin and role of complement inhibitors in ameliorating injury
- Use of monoclonal antibodies to dissect immune mechanisms (Brenner & Rector’s The Kidney, 11th edition)
References
Brenner & Rector’sBrenner & Rector’s The Kidney, 11th editionBrenner & Rector’s The Kidney, 11th edition, Ch. 23