A 28-year-old woman with SLE presents with nephrotic-range proteinuria (4.2 g/day), hematuria with RBC casts, and serum creatinine 2.1 mg/dL. Kidney biopsy shows endocapillary and extracapillary proliferation with fibrinoid necrosis and "wire loop" lesions on light microscopy. The pathology is consistent with the class of lupus nephritis marked **B** in the diagram. Which of the following is the most appropriate INDUCTION therapy for this patient according to current KDIGO 2024 guidelines?

Explanation

## Why Mycophenolate mofetil 2–3 g/day plus high-dose corticosteroids is right Class III/IV (focal/diffuse proliferative) lupus nephritis, marked as **B**, is the most aggressive form, characterized by endocapillary and extracapillary proliferation, fibrinoid necrosis, and "wire loop" lesions (subendothelial immune complex deposits). This class carries high risk for progressive renal failure without treatment and mandates IMMEDIATE AGGRESSIVE IMMUNOSUPPRESSION. According to KDIGO 2024 and current practice (Robbins 10e, Harrison 21e), the standard induction regimen is mycophenolate mofetil (MMF) 2–3 g/day combined with high-dose corticosteroids (often pulse IV methylprednisolone 250–500 mg × 3 days, then oral prednisolone tapered). Voclosporin or belimumab may be added to enhance complete renal response. This patient's presentation (nephrotic-range proteinuria, hematuria with casts, elevated creatinine, and biopsy-proven Class III/IV) is a textbook indication for this regimen. ## Why each distractor is wrong - **Azathioprine 1–2 mg/kg/day plus low-dose prednisolone 10 mg/day**: Azathioprine is a MAINTENANCE agent (used after induction for 3–5 years), not an induction drug. Low-dose prednisolone is insufficient for Class III/IV disease, which requires high-dose induction therapy. This regimen would be inadequate and risks progressive renal failure. - **Rituximab monotherapy 375 mg/m² weekly × 4 weeks**: Rituximab is reserved for REFRACTORY disease (failure to respond to standard induction) or as an adjunct in select cases. It is not first-line induction therapy for Class III/IV lupus nephritis. Monotherapy without corticosteroids and MMF/cyclophosphamide is substandard. - **Angiotensin receptor blocker monotherapy with supportive care**: ARBs provide renal protection in proteinuric disease but have no immunosuppressive effect. Class III/IV lupus nephritis is an active autoimmune process requiring aggressive immunosuppression. ARB monotherapy would allow disease progression and renal failure. **High-Yield:** Class III/IV lupus nephritis = wire loops + crescents + fibrinoid necrosis = AGGRESSIVE disease = MMF or cyclophosphamide + high-dose steroids ± voclosporin/belimumab (KDIGO 2024). [cite: Robbins 10e Ch 6; Harrison 21e Ch 360, 312; KDIGO 2024 Lupus Nephritis Guidelines]