A 7-year-old boy presents with periorbital edema, heavy proteinuria (5g/day), hypoalbuminemia, and hyperlipidemia. Renal biopsy light microscopy is normal. EM shows diffuse effacement of podocyte foot processes with no immune deposits. Which of the following pathophysiological mechanisms best explains the proteinuria?

• A Anti-GBM antibody deposition increasing GBM permeability
• B Complement-mediated lysis of glomerular endothelial cells
• C Loss of charge-dependent filtration barrier due to podocyte injury and nephrin/synaptopodin depletion ✓
• D Mesangial IgA deposition causing mechanical disruption of filtration slits

Explanation

Minimal change disease (MCD), the most common nephrotic syndrome in children, shows no immune deposits and normal light microscopy; only EM reveals diffuse podocyte foot process effacement. The GBM normally carries a strong electronegative charge (from proteoglycans), selectively repelling albumin. Podocyte injury with loss of nephrin (encoded by NPHS1), podocin, and synaptopodin disrupts the filtration slit diaphragm and its charge barrier, allowing massive albumin leakage. T-cell-derived circulating factor(s) are implicated in idiopathic MCD.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.