A 35-year-old woman with a 10-year history of systemic lupus erythematosus (SLE) presents with hematuria, proteinuria (2.5 g/day), and serum creatinine of 1.8 mg/dL. Antinuclear antibody (ANA) is positive, anti-dsDNA titre is elevated, and C3/C4 levels are low. Kidney biopsy shows proliferative lupus nephritis (Class IV) with crescent formation in 15% of glomeruli. What is the drug of choice for induction immunosuppression in this patient?

Explanation

## Diagnosis: Lupus Nephritis Class IV with Crescent Formation The clinical and pathological findings are diagnostic: - SLE with positive ANA and anti-dsDNA antibodies - Active nephritis with hematuria, proteinuria (2.5 g/day), and elevated creatinine - Hypocomplementemia (low C3/C4) — marker of active lupus - Class IV proliferative lupus nephritis with crescent formation (15%) — high-risk disease ## Induction Therapy for Proliferative Lupus Nephritis **High-Yield:** The standard induction regimen for Class III/IV lupus nephritis is: $$\text{Corticosteroids + (Cyclophosphamide OR Mycophenolate Mofetil)}$$ **Key Point:** Both cyclophosphamide and mycophenolate mofetil (MMF) are equally effective for induction, with comparable remission rates (~60–70% at 6 months). Choice depends on: - **Cyclophosphamide:** Preferred in severe disease, RPGN, or crescent formation (as in this case) - **MMF:** Preferred in young women of childbearing age due to lower teratogenicity and gonadal toxicity **Clinical Pearl:** Corticosteroids are ALWAYS part of induction therapy in lupus nephritis. High-dose IV methylprednisolone (500–1000 mg daily × 3 days) followed by oral prednisone (0.5–1 mg/kg/day) is standard. Cyclophosphamide is typically given as IV pulses (0.5–1 g/m² monthly × 6 months) or daily oral dosing. **Mnemonic: LUPUS NEPHRITIS INDUCTION = "COMBO"** - **C**orticosteroids (always) - **O**ne of: Cyclophosphamide or MMF - **M**ycophenolate (alternative to CYC) - **B**oth are evidence-based - **O**ther agents (azathioprine, rituximab) are for maintenance/resistant disease ## Comparison of Induction Regimens | Regimen | Remission Rate | Adverse Effects | Best For | |---------|----------------|-----------------|----------| | **Corticosteroids + CYC** | 60–70% | Gonadal toxicity, infection, hemorrhagic cystitis | Severe disease, RPGN, crescents | | **Corticosteroids + MMF** | 60–70% | GI upset, teratogenicity | Young women, mild-moderate disease | | **Corticosteroids alone** | 30–40% | Inadequate for proliferative disease | Class I/II only | | **Azathioprine** | Not first-line | Hepatotoxicity | Maintenance therapy only | **Warning:** Azathioprine is NOT used for induction; it is reserved for maintenance therapy after remission is achieved with cyclophosphamide or MMF. [cite:Harrison 21e Ch 279; Robbins 10e Ch 20]