Active lupus nephritis requires prompt, structured intervention to preserve kidney function, reduce proteinuria, and achieve a sustained complete renal response. Current evidence supports a combination approach, with therapy sustained over a defined period following response.
This protocol applies to patients with active lupus nephritis initiating first-line systemic treatment. The goal is to induce and maintain complete renal response while minimising long-term glucocorticoid exposure.
Initial therapy begins with a short course of IV pulse glucocorticoids, followed by oral glucocorticoids that are gradually tapered over several months and ultimately withdrawn in patients who achieve a sustained complete renal response.
This is combined with one of several immunosuppressive and/or targeted biologic regimens, chosen according to disease severity and prognostic factors. Background antimalarial therapy is maintained throughout the treatment course.
The primary goals are preservation or improvement of kidney function (GFR ≥80% of baseline within 3 months), a progressive reduction in proteinuria over 6–12 months, and ultimately a complete renal response (urine protein-to-creatinine ratio <500 mg/g). Following response, treatment continues for at least 3 years before gradual withdrawal is considered.
DOI: 10.1016/j.ard.2025.09.007
For patients with active lupus nephritis, IV pulse methylprednisolone is recommended, followed by oral glucocorticoids gradually tapered to ≤5 mg/d prednisone-equivalent by 4–6 months, and slowly withdrawn in patients with sustained complete renal response.
In patients who improve, oral glucocorticoids should be gradually tapered to ≤5 mg/d by 4 to 6 months and ultimately withdrawn by 12 to 24 months.
For patients with active lupus nephritis, especially those with poor prognostic factors, combination therapy of mycophenolate or low-dose intravenous cyclophosphamide with belimumab, mycophenolate with a calcineurin inhibitor (voclosporin or tacrolimus), or mycophenolate with obinutuzumab is recommended. Alternative regimens include single-agent therapy with either mycophenolate or low-dose intravenous cyclophosphamide.
The management of patients with SLE with kidney involvement should align with the general recommendations for SLE, including treatment with hydroxychloroquine.
Treatment should aim for optimisation (preservation or improvement) of kidney function within 3 months, accompanied by a reduction in proteinuria of at least 25% by 3 months, 50% by 6 months, and a UPCR target <700 mg/g by 12 months, and as low as possible afterwards.
Complete renal response should be defined as UPCR <500 mg/g at any time point.
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