A 34-year-old woman with primary nephrotic syndrome (proteinuria 7.2 g/day, albumin 2.1 g/dL) shows minimal change disease on biopsy. She is on prednisolone 1 mg/kg/day for 6 weeks with minimal response. Cyclophosphamide therapy is considered. Which pathophysiological explanation best describes the mechanism of podocyte injury in minimal change disease?
- A T-cell dysregulation producing a circulating permeability factor (possibly soluble urokinase-type plasminogen activator receptor, suPAR) that disrupts podocyte actin cytoskeleton and effacement of foot processes ✓
- B Anti-PLA2R antibody-mediated subepithelial immune complex deposition causing complement activation
- C Complement C3 convertase deficiency causing uncontrolled C3 cleavage and glomerular basement membrane damage
- D Immune complex deposition in the mesangium causing mesangial hypercellularity and GBM thickening
Explanation
Minimal change disease is characterised by absence of immune deposits on immunofluorescence and electron microscopy showing only effacement of podocyte foot processes. The pathophysiology centres on T-cell dysregulation — abnormal T-cell subsets (especially Th2-skewed response) produce circulating permeability factors. suPAR and CD80 overexpression on podocytes have been proposed as mediators; CD80 disrupts nephrin-actin interactions at the podocyte slit diaphragm. Anti-PLA2R antibodies are characteristic of membranous nephropathy. C3 convertase deficiency relates to dense deposit disease/C3 glomerulopathy. Mesangial deposits suggest IgA nephropathy.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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