This protocol addresses a severe, time-sensitive presentation of lupus nephritis: rapidly progressive glomerulonephritis (RPGN) characterised by swift deterioration of kidney function alongside biopsy-confirmed extensive crescent formation affecting more than 50% of glomeruli.
Treatment Approach partial overview
The approach for this presentation includes initial high-dose intravenous corticosteroid pulse therapy followed by intensive immunosuppression — with intravenous cyclophosphamide representing the option most extensively studied in this severe subset. Maintenance immunosuppression follows once response is established, and specific protective measures are incorporated for at-risk patient groups. The complete regimen, including agent selection, sequencing, and the full maintenance strategy, is in the structured protocol below.
Treatment Goals
Key targets include preservation or improvement of kidney function to at least 80% of baseline within 3 months, reduction in proteinuria of at least 25% by 3 months and 50% by 6 months, with a proteinuria target at 12 months and a defined threshold for complete renal response.
References
DOI: 10.1016/j.ard.2025.09.007
This recommendation refers to the specific subset of patients who present with rapidly progressive glomerulonephritis, ie, a rapid decline in kidney function accompanied by histologic evidence of extensive crescent formation (typically affecting >50% of the glomeruli).
In patients with rapidly progressive glomerulonephritis, a short course (6–7 monthly pulses) of high-dose intravenous cyclophosphamide can also be considered.
Although such patients can still be treated with the regimens mentioned in recommendation #4, a short course of high-dose intravenous CYC (modified traditional NIH regimen: 0.5–0.75 g/m² monthly for 6 months, total 6–7 pulses) is an additional option, since it remains the therapeutic regimen most studied in severe LN.
Combination with monthly pulse methylprednisolone has been shown to improve long-term renal outcome without adding toxicity; therefore, the addition of monthly intravenous pulses of methylprednisolone (typically 1 pulse prior to CYC administration) is left to the physician’s discretion.
Administration of monthly gonadotropin-releasing hormone analogs is recommended in premenopausal women who receive high-dose intravenous CYC to maximise the possibility of ovarian preservation.
Mycophenolate or azathioprine should replace cyclophosphamide for those initially treated with cyclophosphamide, alone or in combination with belimumab.
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.
Together with proteinuria, stabilisation (if not improvement) of GFR to ≥80% of baseline value is desirable within the first 3 months to ensure that the patient is not deteriorating and in need of reevaluation of the treatment regimen.
Complete renal response should be defined as UPCR <500 mg/g at any time point.
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