Electron microscopy of a kidney biopsy from a child with nephrotic syndrome shows diffuse effacement of podocyte foot processes with no immune deposits. Light microscopy appears normal. The glomerular protein leak is best explained by loss of which molecular component of the glomerular filtration barrier?

• A Type IV collagen in the glomerular basement membrane
• B Heparan sulfate proteoglycans providing charge barrier in GBM
• C Nephrin at the slit diaphragm of podocytes ✓
• D α-actinin-4 maintaining podocyte cytoskeletal integrity

Explanation

Nephrin is the key transmembrane protein of the slit diaphragm (the main size-selective barrier) and is mutated in congenital nephrotic syndrome of the Finnish type (NPHS1). In minimal change disease (MCD), circulating factors (possibly soluble urokinase receptor or glomerular permeability factor) cause nephrin dysfunction and foot process effacement without immune deposits. Heparan sulfate provides the charge barrier but its selective loss does not fully explain the nephrotic-range proteinuria; the mechanical slit diaphragm is the primary filter for albumin. Type IV collagen mutations cause Alport syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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