A 9-year-old boy has nephrotic syndrome with minimal change on light microscopy, effacement of podocyte foot processes on EM, and no immune deposits. His condition responds completely to steroids. The primary pathogenic mechanism in minimal change disease involves:

• A Autoantibodies against podocin causing slit diaphragm disruption
• B Circulating permeability factor (possibly soluble urokinase receptor) affecting podocyte TRPC6
• C Complement C5b-9 membrane attack complex on podocytes
• D T-cell-derived circulating permeability factor disrupting podocyte charge barrier ✓

Explanation

Minimal change disease (MCD) is strongly linked to T-cell dysfunction, as evidenced by its association with Hodgkin lymphoma, response to immunosuppressives, and relapse with viral infections. The prevailing hypothesis is that a T-cell-derived circulating permeability factor (molecular identity still debated) disrupts the negatively charged glycocalyx (podocalyxin, sialoglycoproteins) on podocytes, causing loss of the charge barrier that normally repels anionic albumin. The primary proteinuria in MCD is highly selective (albumin > larger proteins). Soluble urokinase receptor (suPAR) has been proposed as a permeability factor in FSGS, not MCD; podocin mutations cause congenital nephrotic syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.