A 32-year-old woman with known SLE presents with persistent proteinuria (2.5 g/day), hematuria, and rising serum creatinine (1.8 mg/dL). She is ANA positive and anti-dsDNA positive. Which investigation is most appropriate to assess the severity and type of lupus nephritis?

Explanation

## Diagnostic Approach to Lupus Nephritis **Key Point:** Renal biopsy with light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM) is the gold standard for diagnosing and classifying lupus nephritis. ### Why Renal Biopsy? **High-Yield:** Lupus nephritis is classified into 6 WHO classes (I–VI) based on histopathological findings. Biopsy is essential to: 1. Confirm lupus nephritis diagnosis 2. Determine the class and stage (activity and chronicity indices) 3. Guide treatment intensity and prognosis 4. Identify reversible vs. irreversible changes ### WHO Classification of Lupus Nephritis | Class | Histology | LM | IF Pattern | Prognosis | | --- | --- | --- | --- | --- | | I | Minimal | Normal | Negative or minimal | Excellent | | II | Mesangial | Mesangial proliferation | IgG, IgA, IgM in mesangium | Good | | III | Focal proliferative | <50% glomeruli involved | Granular IgG, C3 (full house) | Fair | | IV | Diffuse proliferative | >50% glomeruli involved | Granular IgG, C3 (full house) | Poor | | V | Membranous | Thickened GBM | Granular IgG along GBM | Variable | | VI | Advanced sclerosis | Global sclerosis | Minimal deposits | Poor | **Clinical Pearl:** The "full house" pattern on immunofluorescence (IgG, IgA, IgM, C3, C1q all positive) is pathognomonic for SLE and helps distinguish it from other glomerulonephritides. ### Diagnostic Algorithm for Lupus Nephritis ```mermaid flowchart TD A[SLE patient with proteinuria/hematuria]:::outcome --> B[Quantify proteinuria and assess renal function]:::action B --> C{Significant renal involvement?}:::decision C -->|Yes| D[Perform renal biopsy]:::action D --> E[Light microscopy classification]:::action E --> F[Immunofluorescence: full house pattern?]:::decision F -->|Yes| G[Lupus nephritis confirmed]:::outcome D --> H[Determine WHO class I-VI]:::action H --> I[Assess activity and chronicity indices]:::action I --> J[Guide immunosuppressive therapy]:::action C -->|No| K[Monitor with serology and urinalysis]:::action ``` **Mnemonic:** **FULL HOUSE** immunofluorescence = **F**ibrinogen, **U**nknown (C1q), **L**ight chain (IgG, IgA, IgM), **L**ow density (C3) — all positive in SLE.