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Biopsy-proven proliferative and membranous lupus nephritis with a continuing but incomplete early proteinuric

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ModerateLupus NephritisBiopsy-proven proliferative and membranous lupus nephritis with a continuing but incomplete early proteinuric responseSCE Rheumatology

A 29-year-old woman with systemic lupus erythematosus has biopsy-proven class IV-G (A) plus class V lupus nephritis. At presentation, her urine protein:creatinine ratio (UPCR) was 400 mg/mmol, serum albumin 24 g/L and eGFR 78 mL/min/1.73 m². She received intravenous methylprednisolone followed by tapering oral prednisolone, mycophenolate mofetil 1.5 g twice daily and hydroxychloroquine. Renin–angiotensin system blockade has been optimised. At 3 months, her UPCR was 286 mg/mmol. At 6 months, it is 216 mg/mmol, serum albumin is 30 g/L and eGFR is 76 mL/min/1.73 m². Urinary red-cell casts have resolved. Prednisolone has been tapered to 5 mg daily. She reports taking treatment consistently, pharmacy records show regular dispensing, and there has been no infection or drug toxicity. Which is the most appropriate next management step?

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Correct answer: C — Verify adherence and drug exposure, then continue current therapy with close review

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

Her UPCR fell by 28.5% at 3 months, meeting the ≥25% early milestone. By 6 months it has fallen by 46%, narrowly missing the usual ≥50% target, while eGFR remains stable, serum albumin is improving and active urinary sediment has resolved. This is therefore a continuing renal response rather than unequivocal refractory nephritis. Before labelling lupus nephritis non-responsive, adherence, prescribed dose and drug exposure where available should be reviewed. A further period on the current regimen with close reassessment is reasonable when proteinuria continues to decline, particularly after nephrotic-range baseline proteinuria and with stable kidney function. A is premature: switching to cyclophosphamide is appropriate for genuine inadequate response after excluding remediable causes, not automatically for narrowly missing one milestone despite continued improvement. B is similarly premature; rituximab is generally reserved for refractory disease. C may be appropriate when clinical findings are discordant or there is uncertainty about persistent activity, chronic damage or a change in pathology, but routine immediate re-biopsy is not required here. E is inappropriate because azathioprine is a maintenance alternative after an adequate initial response, whereas she still has substantial proteinuria and should not have effective induction therapy de-escalated.

Reference: EULAR recommendations for the management of systemic lupus erythematosus with kidney involvement: 2025 update (Online 16 October 2025; print January 2026) — https://pubmed.ncbi.nlm.nih.gov/41107121/ Practical insights for the clinical implementation of the EULAR recommendations for patients with systemic lupus erythematosus (2025) — https://rmdopen.bmj.com/content/11/4/e006210 2019 Update of the Joint EULAR/ERA–EDTA recommendations for the management of lupus nephritis (2020) — https://ard.bmj.com/content/79/6/713.full.pdf