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Active proliferative lupus nephritis with a membranous component — SCE Rheumatology MCQ

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ModerateACR GuidelinesActive proliferative lupus nephritis with a membranous componentSCE Rheumatology

A 34-year-old woman with systemic lupus erythematosus undergoes kidney biopsy because of oedema, glomerular haematuria and increasing proteinuria. Histology demonstrates active class III(A) lupus nephritis with a class V component. There are no cellular crescents, fibrinoid necrosis, severe interstitial inflammation or significant chronic lesions. Her urine protein:creatinine ratio is 3.8 g/g, serum albumin 27 g/L and eGFR 76 mL/min/1.73 m². Blood pressure is 128/78 mmHg on losartan. She has no clinically significant extrarenal lupus activity, active infection or contraindication to calcineurin inhibition. She takes hydroxychloroquine, is not pregnant and uses effective contraception. Applying the phenotype-based initial treatment strategy in the 2024 American College of Rheumatology lupus nephritis guideline, while restricting treatment to an option supported for NHS use, which regimen is most appropriate?

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Correct answer: E — Pulse intravenous glucocorticoids followed by an oral taper, with mycophenolate mofetil and voclosporin

Explanation lettering: E = shown as B · B = shown as D · D = shown as E

This is active proliferative lupus nephritis with a membranous component and marked proteinuria. The ACR strategy conditionally favours triple therapy—glucocorticoids plus two immunosuppressive agents—over conventional glucocorticoid–immunosuppressant dual therapy. Within that strategy, proteinuria of at least 3 g/g, preserved kidney function and absence of a calcineurin-inhibitor contraindication favour a mycophenolic acid analogue plus a calcineurin inhibitor rather than a belimumab-based combination. Voclosporin with mycophenolate is specifically recommended by NICE for adults with active class III–V lupus nephritis, including mixed class III/V disease. A is a valid triple regimen and is particularly attractive when important extrarenal disease, impaired kidney function or significant hypertension makes calcineurin inhibition less suitable; those features are absent. B is also an ACR-listed combination, but there is no reason to substitute cyclophosphamide for mycophenolate here. C remains a recognised treatment backbone but omits the additional agent favoured by the ACR combination strategy. E may be selected for severe proliferative nephritis with adverse prognostic features such as declining eGFR, crescents, fibrinoid necrosis or severe interstitial inflammation; none is present. Initial intravenous glucocorticoid pulses should be followed by a prompt oral taper to minimise cumulative toxicity.

Reference: Voclosporin with mycophenolate mofetil for treating lupus nephritis: Recommendations (3 May 2023) — https://www.nice.org.uk/guidance/ta882/chapter/1-Recommendations Voclosporin with mycophenolate mofetil for treating lupus nephritis: Committee discussion (3 May 2023) — https://www.nice.org.uk/guidance/TA882/chapter/3-committee-discussion 2024 American College of Rheumatology Guideline for the Screening, Treatment, and Management of Lupus Nephritis (7 May 2025) — https://pubmed.ncbi.nlm.nih.gov/40127995/