A 7-year-old child with nephrotic syndrome undergoes renal biopsy showing normal light microscopy, no immune deposits on immunofluorescence, and diffuse effacement of podocyte foot processes on electron microscopy. The primary pathophysiological defect responsible for proteinuria in this condition is:
- A Mesangial IgA deposition activating complement C3 convertase
- B Basement membrane splitting due to COL4A3 mutation
- C Loss of nephrin-podocin slit diaphragm integrity and reduction of glomerular charge barrier due to loss of podocalyxin ✓
- D Subepithelial immune complex deposition activating complement membrane attack complex
Explanation
Minimal change disease (MCD) is characterised by diffuse podocyte foot process effacement on EM with no immune deposits — a hallmark of podocyte injury without immunoglobulin-mediated mechanism. The slit diaphragm between adjacent foot processes is the critical filtration barrier, formed by nephrin-podocin complexes. In MCD, a circulating factor (possibly a T-cell-derived permeability factor) disrupts podocyte cytoskeleton and nephrin expression, effacing foot processes. Additionally, podocalyxin, a highly negatively charged sialoglycoprotein on podocyte surfaces, is reduced, abolishing the glomerular electronegativity charge barrier. Both structural and charge barrier defects contribute to selective (albumin-predominant) proteinuria. Mesangial IgA deposits characterise IgA nephropathy; COL4A3 mutations cause Alport syndrome; subepithelial deposits characterise membranous nephropathy.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.