A 28-year-old woman with systemic lupus erythematosus presents with progressive renal dysfunction and proteinuria. Kidney biopsy is performed. Which of the following is the most common histopathological pattern of lupus nephritis?

Explanation

## Lupus Nephritis Classification and Epidemiology **Key Point:** Class IV (diffuse proliferative) lupus nephritis is the most common and most severe form of lupus nephritis, accounting for approximately 40–50% of all lupus nephritis cases and the majority of symptomatic presentations. ### WHO/ISN-RPS Classification of Lupus Nephritis | Class | Histology | Prevalence | Prognosis | Clinical Features | |-------|-----------|-----------|-----------|-------------------| | I | Minimal mesangial | 5–10% | Excellent | Asymptomatic, normal renal function | | II | Mesangial proliferative | 10–15% | Good | Mild proteinuria, normal GFR | | III | Focal proliferative (<50% glomeruli) | 20–25% | Fair | Hematuria, proteinuria, mild renal dysfunction | | **IV** | **Diffuse proliferative (>50% glomeruli)** | **40–50%** | **Poor** | **Heavy proteinuria, hematuria, renal insufficiency** | | V | Membranous | 10–20% | Variable | Nephrotic syndrome, proteinuria | | VI | Advanced sclerosing | 5% | Very poor | End-stage renal disease | **High-Yield:** Class IV is subdivided into: - **IV-S (segmental):** <50% of glomerular tuft involvement - **IV-G (global):** ≥50% of glomerular tuft involvement Class IV-G carries the worst prognosis and is most likely to progress to ESRD without treatment. ### Clinical Correlation **Clinical Pearl:** Patients with Class IV lupus nephritis typically present with: - Heavy proteinuria (often >3.5 g/day, nephrotic range) - Active urinary sediment (RBC casts, WBC casts) - Hypertension - Declining GFR - Elevated anti-dsDNA antibodies and low complement (C3, C4) ### Pathophysiology Class IV nephritis involves **immune complex deposition** in the subendothelial space and along the glomerular basement membrane, triggering: 1. Complement activation (C1q, C3, C4 deposition) 2. Endocapillary or extracapillary proliferation 3. Wire-loop lesions (pathognomonic for SLE) 4. Hematoxylin bodies (also pathognomonic) **Warning:** Do not confuse Class IV with Class III based on severity alone — the distinction is based on the percentage of glomeruli involved, not clinical severity. However, Class IV is statistically more severe. ### Treatment Implications Class IV lupus nephritis requires aggressive immunosuppression: - Induction: IV methylprednisolone + cyclophosphamide or mycophenolate mofetil - Maintenance: Azathioprine or mycophenolate mofetil + oral corticosteroids - Remission rates: 50–70% with modern regimens **Mnemonic: LUPUS Nephritis Classes — "Most Common = Most Severe"** - **L**esions: Class IV has diffuse (most) lesions - **U**sually: Class IV is the usual presentation in symptomatic SLE - **P**roliferative: Class IV is diffuse proliferative - **U**nfavorable: Class IV has unfavorable prognosis without treatment - **S**everity: Class IV correlates with worst outcomes