In minimal change disease (MCD), the glomeruli appear normal on light microscopy but electron microscopy shows diffuse podocyte foot process effacement. What is the current evidence-supported primary pathogenic hypothesis for MCD?
- A Anti-nephrin antibodies causing direct podocyte injury
- B Complement C5b-9 membrane attack complex forming on podocytes
- C T-cell–derived circulating permeability factor (possibly CD80/B7.1 upregulation on podocytes) causing loss of glomerular charge barrier ✓
- D Podocin gene mutation causing primary slit diaphragm dysfunction
Explanation
MCD is believed to be mediated by a circulating T-cell–derived permeability factor that disrupts the anionic charge barrier of the glomerular basement membrane, resulting in selective proteinuria (predominantly albumin). Current evidence implicates aberrant T-cell activation leading to cytokine (possibly IL-13, IL-4) or direct CD80 upregulation on podocytes, impairing slit diaphragm signalling. This explains the dramatic response to corticosteroids and immunosuppressants. Anti-nephrin antibodies are now recognised in some cases of MCD especially in adults. Podocin mutations cause hereditary FSGS, not MCD.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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