A 35-year-old woman presents with nephrotic syndrome characterized by proteinuria (8 g/day), hypoalbuminemia, and edema. Light microscopy 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 patient?

## Most Common Cause of Nephrotic Syndrome in Adults **Key Point:** Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, accounting for approximately 40–50% of cases in developed countries and 10–15% in developing nations. In India, it ranks second after focal segmental glomerulosclerosis (FSGS) but remains the most common primary glomerulonephritis presenting with nephrotic syndrome in older adults. ### Pathological Features of Membranous Nephropathy | Feature | Finding | |---------|----------| | **Light Microscopy** | Diffuse thickening of glomerular basement membrane (GBM); normal cellularity | | **Electron Microscopy** | "Spike and dome" appearance (subepithelial immune deposits with GBM projections) | | **Immunofluorescence** | Granular IgG and C3 deposits along GBM | | **Clinical Presentation** | Nephrotic syndrome (proteinuria >3.5 g/day, hypoalbuminemia, edema, hyperlipidemia) | ### Epidemiology and Associations **Primary (Idiopathic) MN:** - Most common form (75–80% of cases) - Associated with anti-phospholipase A2 receptor (anti-PLA2R) antibodies in 70–80% of cases - Peak incidence: 40–60 years **Secondary MN:** - Systemic lupus erythematosus (SLE) — most common secondary cause - Malignancy (lung, breast, colon, gastric cancers) - Infections: hepatitis B, syphilis, malaria - Medications: NSAIDs, gold, penicillamine **Clinical Pearl:** The "spike and dome" appearance is pathognomonic for membranous nephropathy. The "spikes" are projections of the GBM that extend over the immune deposits, creating a characteristic electron microscopic pattern. **High-Yield:** In adults, the differential diagnosis of nephrotic syndrome includes: 1. Membranous nephropathy (40–50%) 2. Focal segmental glomerulosclerosis (20–25%) 3. Minimal change disease (10–15%) 4. Membranoproliferative GN (5–10%) ### Natural History and Prognosis - Approximately 30–40% of patients achieve spontaneous remission - 30–40% develop progressive renal insufficiency - 20–30% have persistent nephrotic syndrome without renal dysfunction - Presence of hypertension and reduced GFR at presentation are poor prognostic factors **Mnemonic: SPAM** — Secondary causes of membranous nephropathy: - **S**LE (systemic lupus erythematosus) - **P**ancreatic cancer, Prostate cancer - **A**nti-PLA2R antibodies (primary), Autoimmune hepatitis - **M**alignancy, Medications (NSAIDs, gold) [cite:Robbins 10e Ch 20]