A renal biopsy from a 10-year-old child with nephrotic syndrome shows normal light microscopy, negative immunofluorescence, and electron microscopy demonstrating diffuse effacement of podocyte foot processes. Which of the following mechanisms BEST explains the massive proteinuria?
- A Loss of the podocyte slit diaphragm charge and size barrier due to nephrin and podocin dysfunction ✓
- B Deposition of immune complexes in the subepithelial space disrupting the GBM
- C Anti-GBM antibodies targeting type IV collagen alpha-3 chain
- D Mesangial IgA deposition activating complement via the lectin pathway
Correct answer: A. Loss of the podocyte slit diaphragm charge and size barrier due to nephrin and podocin dysfunction
Explanation
Minimal change disease (MCD) proteinuria results from podocyte injury and effacement of foot processes, causing loss of the nephrin-podocin slit diaphragm complex that normally restricts albumin passage. A circulating permeability factor (possibly suPAR or IL-13) may injure podocytes. Anti-GBM antibodies characterise Goodpasture disease; mesangial IgA characterises IgA nephropathy.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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