A 28-year-old woman with SLE on hydroxychloroquine has new-onset nephrotic-range proteinuria (4.8 g/day), haematuria, and creatinine 1.9 mg/dL. Anti-dsDNA titre is high and C3/C4 are low. Renal biopsy shows diffuse proliferative changes with 'wire-loop' deposits on light microscopy. Which ISN/RPS class is this and what is the first-line treatment?

• A Class II lupus nephritis — hydroxychloroquine dose escalation alone
• B Class V lupus nephritis — MMF alone without steroids
• C Class III lupus nephritis — tacrolimus monotherapy
• D Class IV lupus nephritis — mycophenolate mofetil (MMF) or cyclophosphamide (Euro-lupus or NIH protocol) plus high-dose steroids ✓

Explanation

Diffuse proliferative glomerulonephritis with wire-loop deposits (subendothelial immune deposits) affecting > 50% of glomeruli is ISN/RPS Class IV lupus nephritis — the most severe form requiring aggressive immunosuppression. Induction therapy is mycophenolate mofetil (2-3 g/day) or cyclophosphamide (Euro-lupus low-dose or NIH high-dose) combined with high-dose corticosteroids. Class II shows mesangial disease only (mild, no aggressive treatment). Class V is membranous LN (subepithelial deposits). Class III involves < 50% of glomeruli (focal proliferative).

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

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Written and medically reviewed by the StethoPrep medical team.