## Induction Therapy for Lupus Nephritis **Key Point:** Cyclophosphamide is the gold-standard induction agent for severe lupus nephritis (Class III and IV), particularly in patients with rapidly progressive disease or risk of renal failure. ### Pathophysiology of Lupus Nephritis Lupus nephritis results from immune complex deposition in the glomerulus, triggering complement activation and glomerular inflammation. Class IV (diffuse proliferative) lupus nephritis carries the highest risk of progression to end-stage renal disease without aggressive immunosuppression. ### Induction vs. Maintenance Therapy | Phase | Goal | Drug of Choice | Duration | |-------|------|---------------|-----------| | **Induction** | Rapid remission, prevent renal failure | Cyclophosphamide (IV pulses) | 3–6 months | | **Maintenance** | Sustain remission, minimize toxicity | Mycophenolate mofetil or azathioprine | 2–3 years | **High-Yield:** The Euro-Lupus Nephritis Trial (ELNT) and NIH protocols established cyclophosphamide as the standard induction therapy for Class III and IV lupus nephritis due to superior renal outcomes compared to other agents. ### Cyclophosphamide Regimen 1. **Dosing:** IV pulses of 500–1000 mg/m² given monthly for 6 months (or alternate-month dosing) 2. **Concurrent therapy:** High-dose corticosteroids (IV methylprednisolone followed by oral prednisone taper) 3. **Mesna:** Co-administered to prevent hemorrhagic cystitis 4. **Hydration:** Aggressive IV hydration to minimize bladder toxicity **Clinical Pearl:** Cyclophosphamide's superior efficacy in lupus nephritis stems from its ability to rapidly deplete B and T lymphocytes, breaking the autoimmune cycle more effectively than other agents. ### Adverse Effects Requiring Monitoring - **Hemorrhagic cystitis** (prevented by mesna + hydration) - **Infertility** (offer egg/sperm banking before therapy) - **Infections** (opportunistic and bacterial) - **Secondary malignancy** (long-term risk) - **Bladder cancer** (cumulative dose-dependent) **Warning:** Do NOT confuse induction with maintenance therapy. Cyclophosphamide is used for induction; mycophenolate mofetil or azathioprine are preferred for maintenance due to better long-term tolerability. ### Post-Induction Maintenance After cyclophosphamide induction (3–6 months), patients transition to mycophenolate mofetil (1–3 g/day) or azathioprine (1–2 mg/kg/day) for sustained remission and reduced toxicity. [cite:Harrison 21e Ch 319; KD Tripathi 8e Ch 76]
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