A 35-year-old woman presents with nephrotic syndrome (proteinuria 4.5 g/day, hypoalbuminemia, edema). Kidney biopsy shows diffuse thickening of the glomerular basement membrane with a characteristic 'spike and dome' appearance on electron microscopy. What is the most common cause of nephrotic syndrome in this histological pattern?
A. IgA nephropathy
B. Focal segmental glomerulosclerosis
C. Minimal change disease
D. Membranous nephropathy
Explanation
Diagnosis: Membranous Nephropathy
Key Point
Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, accounting for 30–40% of cases in developed countries and 10–20% in Asia.
Histological Features
Table
Feature
Membranous Nephropathy
Light microscopy
Diffuse thickening of GBM; normal cellularity
Electron microscopy
Spike and dome appearance (subepithelial immune deposits with GBM projections)
Immunofluorescence
Granular IgG and C3 deposits along capillary wall
Stage
Stage I–IV (based on EM appearance)
Pathogenesis
1.
Primary (idiopathic) — 75% of cases; autoantibodies to phospholipase A2 receptor (PLA2R) or thrombospondin type-1 domain-containing 7A (THSD7A)
2.
Secondary — 25% of cases; associated with malignancy (lung, gastric, colon cancer), infections (HBV, HCV, syphilis), autoimmune disease (SLE, rheumatoid arthritis), or drugs (NSAIDs, penicillamine)
Clinical Presentation
High-YieldNEET PG
MN typically presents with:
Nephrotic-range proteinuria (>3.5 g/day)
Preserved renal function initially (unlike FSGS)
Hematuria in 30–50% of cases
Hypertension in 50% of cases
Risk of thromboembolism (hypercoagulability from loss of anticoagulant proteins)
Management
Clinical Pearl
Spontaneous remission occurs in 20–30% of patients; therefore, observation is acceptable in low-risk patients. High-risk patients (persistent proteinuria >4 g/day, declining GFR, or serum creatinine >1.3 mg/dL) require immunosuppressive therapy (corticosteroids ± cyclophosphamide or calcineurin inhibitors).
Mnemonic: SPIKE AND DOME — Subepithelial deposits, Projections of GBM, Immune complexes, Kidney biopsy finding, E (electron microscopy) — characteristic of Membranous Nephropathy.
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