A 7-year-old child with idiopathic nephrotic syndrome undergoes renal biopsy. Electron microscopy shows diffuse foot process effacement and microvillous transformation of podocytes. Light microscopy and immunofluorescence are essentially normal. The major molecular target of the circulating permeability factor in this condition is:

• A Nephrin (NPHS1), disrupting the slit diaphragm structure
• B CD80 (B7-1) upregulation on podocytes, disrupting the neph1-CD2AP complex ✓
• C Podocin (NPHS2), causing misfolding and ER retention
• D Heparanase degradation of glomerular basement membrane heparan sulfate proteoglycans

Explanation

In minimal change disease (MCD), a circulating T-cell-derived permeability factor upregulates CD80 (B7-1) expression on podocytes. Normally podocyte CD80 expression is suppressed by the regulatory molecule CTLA-4 and by soluble urokinase plasminogen activator receptor (suPAR). CD80 upregulation disrupts the β1-integrin signaling and cytoskeletal organization of podocytes, causing foot process effacement. Interestingly, urinary CD80 levels are elevated in MCD relapses but not in FSGS, offering a diagnostic utility. Nephrin (NPHS1) mutations cause congenital nephrotic syndrome of the Finnish type; podocin (NPHS2) mutations cause familial FSGS; heparanase is implicated in diabetic nephropathy and some other glomerulopathies.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.