A 34-year-old woman with SLE has been on hydroxychloroquine for 2 years. She now presents with proteinuria 2.8 g/day, haematuria, and creatinine 1.6 mg/dL. Renal biopsy shows diffuse proliferative glomerulonephritis (Class IV). What is the preferred induction therapy according to current ACR guidelines?

• A Hydroxychloroquine dose escalation alone
• B Azathioprine plus low-dose corticosteroids
• C Cyclophosphamide (NIH protocol) as the only acceptable induction agent
• D Mycophenolate mofetil (MMF) 2–3 g/day plus high-dose corticosteroids ✓

Explanation

For Class III/IV lupus nephritis, ACR 2024 guidelines recommend mycophenolate mofetil (2–3 g/day) or low-dose IV cyclophosphamide (Euro-Lupus protocol) plus high-dose corticosteroids as induction therapy. MMF has equivalent efficacy to NIH cyclophosphamide with a better side-effect profile. Belimumab or voclosporin can be added as adjuncts. Hydroxychloroquine alone is insufficient for active nephritis. Azathioprine is used for maintenance, not induction of Class IV.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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