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Systemic lupus nephritis — ABIM Board MCQ

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HardRheumatology/Allergy/ImmunologySystemic lupus nephritisABIM Board

A 29-year-old woman with systemic lupus erythematosus treated with hydroxychloroquine develops edema and active inflammatory arthritis. Urinalysis shows dysmorphic erythrocytes and erythrocyte casts, and 24-hour urine protein excretion is 2.8 g. Serum complement levels are low, anti–double-stranded DNA antibody titers are elevated, and serum creatinine is 1.2 mg/dL. Kidney biopsy shows active class IV lupus nephritis without advanced chronic scarring or thrombotic microangiopathy. A pregnancy test is negative, and she agrees to use reliable contraception. Hydroxychloroquine will be continued. According to current US guidance, which of the following is the most appropriate initial kidney-directed regimen?

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Correct answer: E — Glucocorticoids plus mycophenolate mofetil and belimumab

Active class IV lupus nephritis is proliferative glomerulonephritis requiring prompt combination immunosuppression. Current ACR guidance favors pulse glucocorticoids followed by a tapered oral regimen plus two additional immunosuppressive agents. Mycophenolate mofetil with belimumab is an accepted triple regimen, particularly appropriate here because kidney function is preserved and she also has active extrarenal disease. Hydroxychloroquine and renin-angiotensin system blockade are useful adjuncts but cannot control proliferative nephritis alone. Azathioprine is used primarily for maintenance or when pregnancy compatibility is required and is less effective for initial proliferative disease. Plasma exchange is not routine therapy in stable lupus nephritis without thrombotic microangiopathy, anti-GBM disease, or another specific indication. Rituximab is generally reserved for inadequate response or refractory disease rather than routine first-line treatment.

Reference: Sammaritano LR, et al. 2024 American College of Rheumatology Guideline for the Screening, Treatment, and Management of Lupus Nephritis, recommendations for active lupus nephritis. Published 2025. https://pubmed.ncbi.nlm.nih.gov/40331662/