A 32-year-old Indian woman presents with insidious onset of ankle swelling and facial puffiness for 3 weeks. She reports foamy urine and weight gain of 4 kg. On examination: BP 128/82 mmHg, bilateral ankle edema, ascites present. Urinalysis shows 3+ proteinuria, no RBCs or casts. Serum albumin 2.1 g/dL, total cholesterol 320 mg/dL, serum creatinine 0.9 mg/dL. Renal biopsy shows capillary wall thickening with subepithelial "spike and dome" deposits on electron microscopy. What is the most likely diagnosis?

Explanation

## Diagnosis: Membranous Nephropathy ### Clinical Presentation **Key Point:** The patient presents with classic nephrotic syndrome (proteinuria >3.5 g/day, hypoalbuminemia, hyperlipidemia, edema) with preserved renal function (creatinine 0.9 mg/dL). ### Pathognomonic Electron Microscopy Finding **High-Yield:** The "spike and dome" (or "subepithelial hump") appearance on electron microscopy is pathognomonic for membranous nephropathy. This represents immune complex deposits (IgG and C3) in the subepithelial space with intervening basement membrane projections. ### Light Microscopy Features - Capillary wall thickening ("wire-loop" appearance on light microscopy) - No cellular proliferation - Basement membrane appears thickened and uniform ### Immunofluorescence Pattern **Clinical Pearl:** "Granular" pattern of IgG and C3 along the glomerular basement membrane is characteristic, distinguishing it from linear (anti-GBM disease) or absent (minimal change) patterns. ### Etiology in Adults | Feature | Primary | Secondary | | --- | --- | --- | | Frequency | 75% of cases | 25% of cases | | Common causes | Idiopathic | Malignancy, SLE, drugs (NSAIDs, penicillamine) | | PLA2R antibody | Positive in ~70% | Usually negative | | Prognosis | Variable | Depends on underlying disease | **Key Point:** In a 32-year-old woman with no systemic features and pure nephrotic presentation, primary membranous nephropathy is most likely. ### Natural History - Spontaneous remission: ~20–30% - Persistent proteinuria: ~40–50% - Progressive renal failure: ~20–30% **Mnemonic:** **SPIKE AND DOME** = **S**ubepithelial deposits, **P**rojections of **I**mmune complexes, **K**eep **E** (electron microscopy) in mind — **A**nd **D**istinguish from **O**ther **M**embranous **E**ntities.