Treatment of SLE in Active Lupus Nephritis with Reduced Glomerular Filtration
Clinical scenario
This protocol applies to patients with systemic lupus erythematosus who have active lupus nephritis and are at high risk for renal failure — defined by a reduced glomerular filtration rate, histological presence of cellular crescents or fibrinoid necrosis, or severe interstitial inflammation.
Key finding: High-risk lupus nephritis
When active lupus nephritis is accompanied by reduced GFR, crescentic or fibrinoid histological changes, or severe interstitial inflammation, prompt escalation of treatment is required. These findings identify a subset at elevated risk of irreversible renal injury.
Treatment approach — partial overview
The protocol involves high-dose intravenous cyclophosphamide combined with pulse intravenous methylprednisolone; the complete induction strategy, maintenance phase, and sequencing are available in the full protocol below.
Treatment targets
Success is defined as a reduction in proteinuria of at least 25% by 3 months, at least 50% by 6 months, and below 500–700 mg/day at 12 months — all with the glomerular filtration rate maintained within 10% of baseline.
References
DOI: 10.1136/ard-2023-224762
- In patients at high-risk for renal failure (defined as reduced GFR, histological presence of cellular crescents or fibrinoid necrosis, or severe interstitial inflammation), high-dose (National Institutes of Health regimen) intravenous cyclophosphamide (1a/A) in combination with pulse intravenous methylprednisolone, can be considered.
- For patients presenting with impaired kidney function or histological evidence of crescentic glomerulonephritis and/or severe interstitial inflammation, the traditional high-dose intravenous CYC regimen can also be considered, since it is the most extensively studied therapeutic regimen in severe LN, in the early studies from the NIH.
- Following renal response, treatment of lupus nephritis should continue for at least 3 years; azathioprine or mycophenolate should replace cyclophosphamide for those initially treated with cyclophosphamide alone or in combination with belimumab.
- Following the choice of initial treatment, renal response should be monitored according to the 2019 EULAR/ERA-EDTA targets (reduction in proteinuria ≥25% and 50% at 3 and 6 months, respectively, and below 500–700 mg/day at 12 months, all with GFR within 10% from baseline).
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