A 35-year-old woman with lupus nephritis (WHO Class IV, diffuse proliferative) presents with haematuria, RBC casts, proteinuria 2.5 g/day, and serum creatinine 1.8 mg/dL. Complement levels are low (C3, C4). What is the drug of choice for induction immunosuppression in this patient?

Explanation

## Induction Therapy for Lupus Nephritis Class IV **Key Point:** Lupus nephritis WHO Class IV (diffuse proliferative) is the most severe form and requires aggressive induction immunosuppression. Intravenous cyclophosphamide (IV CYC) is the gold-standard first-line agent for inducing remission. **High-Yield:** The KDIGO 2021 Lupus Nephritis guidelines recommend IV cyclophosphamide as the preferred induction regimen for Class IV LN because: - Superior remission rates (60–80%) compared to corticosteroids alone - Proven to delay progression to ESRD - Standard dosing: 0.5–1 g/m² IV monthly for 6 months (or 500–1000 mg fixed dose) - Must be combined with corticosteroids (prednisolone 0.5–1 mg/kg/day, tapered) - Mesna co-administration mandatory to prevent haemorrhagic cystitis **Mnemonic:** CYC-LN = **Cyclophosphamide for Lupus Nephritis** (Class IV) **Clinical Pearl:** This patient has: - Active proliferative disease (RBC casts, haematuria) - Significant proteinuria (2.5 g/day) - Reduced GFR (creatinine 1.8) - Low complement (active lupus activity) These features mandate aggressive induction, not monotherapy. **Induction vs. Maintenance Paradigm:** ```mermaid flowchart TD A[Lupus Nephritis Class IV]:::outcome --> B[Induction Phase<br/>6 months]:::action B --> C[IV Cyclophosphamide<br/>+ Prednisolone]:::action C --> D{Remission achieved?}:::decision D -->|Yes| E[Maintenance Phase<br/>2–3 years]:::action D -->|No| F[Switch to MMF or<br/>repeat CYC]:::action E --> G[Azathioprine or MMF<br/>+ low-dose prednisolone]:::action ``` **Adverse Effects & Monitoring:** - Haemorrhagic cystitis → use mesna, hydration, frequent voiding - Infection risk → prophylactic TMP-SMX - Infertility (especially in women) → counsel before therapy - Monitor CBC, creatinine, urinalysis monthly during induction **Alternative Regimen:** Mycophenolate mofetil (MMF) 3 g/day is now considered non-inferior to IV CYC in some trials (ALMS, Aspreva) but is typically reserved for maintenance or in patients unable to tolerate CYC. [cite:KDIGO 2021 Lupus Nephritis; Harrison 21e Ch 319]