A 32-year-old woman presents with nephrotic syndrome (proteinuria 8 g/day, serum albumin 2.1 g/dL, edema). Kidney biopsy shows diffuse capillary wall thickening with subepithelial immune deposits in a 'spike and dome' pattern on electron microscopy. Which of the following is NOT a typical feature of membranous nephropathy?

Explanation

## Membranous Nephropathy — Key Features **Key Point:** Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults and presents with **selective proteinuria** (predominantly albumin loss), preserved renal function early on, and characteristic subepithelial 'spike and dome' immune deposits. ### Urinary Findings in Membranous Nephropathy | Feature | Typical Pattern | |---------|----------------| | **Proteinuria** | Selective (albumin >α2-macroglobulin); often >3.5 g/day | | **Hematuria** | Absent or microscopic (<5 RBC/hpf) | | **RBC casts** | **NOT typical** — suggests glomerulonephritis (PSGN, RPGN) | | **Lipiduria** | Present (oval fat bodies, fatty casts) | | **WBC casts** | Absent | **High-Yield:** RBC casts and active hematuria are **red flags** that point away from pure membranous nephropathy and suggest: - Post-streptococcal GN (PSGN) - IgA nephropathy - Rapidly progressive GN (RPGN) - Lupus nephritis (Class III/IV) ### Diagnostic & Clinical Features of MN **Key Point:** Primary membranous nephropathy is now recognized as an **autoimmune disease**: - Anti-PLA2R (phospholipase A2 receptor) antibodies: positive in 70–80% of primary MN - Anti-THSD7A antibodies: positive in 5–10% of seronegative cases - Selective proteinuria with preserved GFR early (hallmark) **Clinical Pearl:** Secondary membranous nephropathy occurs with: - Malignancy (lung, gastric, breast, colon) - Infections (hepatitis B, syphilis, malaria) - Medications (NSAIDs, gold, penicillamine) - Autoimmune disease (SLE, rheumatoid arthritis) ### Thromboembolism Risk in MN **High-Yield:** Patients with nephrotic syndrome (including MN) lose: - Antithrombin III - Protein C and S - Plasminogen - Albumin (carries anticoagulant factors) This results in a **hypercoagulable state** with increased risk of: - Deep vein thrombosis (DVT) - Pulmonary embolism (PE) - Renal vein thrombosis (especially in MN) **Warning:** Do NOT confuse membranous nephropathy with membranoproliferative GN — the latter has **endocapillary proliferation** and typically presents with hematuria and RBC casts. ### Why the Correct Answer is Correct **Hematuria and RBC casts are NOT typical of membranous nephropathy.** MN is characterized by **selective proteinuria without active urinary sediment**. The presence of RBC casts indicates glomerular inflammation and proliferation, which is incompatible with the pure capillary wall disease seen in MN. This finding should prompt investigation for alternative diagnoses (PSGN, IgA nephropathy, RPGN, or lupus).