Initial Treatment Approach for Lupus Nephritis

Treatment Selection Algorithm

The American College of Rheumatology recommends glucocorticoids plus one of the following for patients with active Class III or IV lupus nephritis: mycophenolic acid analogs, low-dose intravenous cyclophosphamide, belimumab combined with either mycophenolic acid analogs or cyclophosphamide, or mycophenolic acid analogs with a calcineurin inhibitor 1, 2
For patients with Class III/IV lupus nephritis, the European League Against Rheumatism suggests mycophenolic acid analogs (target dose: 3 g/day for 6 months) as a first-line option 2
The American College of Rheumatology recommends low-dose intravenous cyclophosphamide (total dose 3 g over 3 months) as an alternative option for patients with Class III/IV lupus nephritis 2
Belimumab combined with either mycophenolic acid analogs or low-dose cyclophosphamide is recommended for patients with Class III/IV lupus nephritis by the American College of Rheumatology 1
Mycophenolic acid analogs with a calcineurin inhibitor (voclosporin, tacrolimus) are recommended for patients with Class III/IV lupus nephritis and eGFR >45 ml/min/1.73m² by the American College of Rheumatology 1

The European League Against Rheumatism recommends initial treatment with three consecutive pulses of intravenous methylprednisolone (500-750 mg each) for patients with lupus nephritis 2
The American College of Rheumatology suggests follow-up treatment with oral prednisone 0.5 mg/kg/day for 4 weeks 2
Tapering to ≤10 mg/day by 4-6 months is recommended by the European League Against Rheumatism 2

The American College of Rheumatology recommends hydroxychloroquine for all patients with lupus nephritis to improve outcomes by reducing renal flares and limiting renal and cardiovascular damage 2
The European League Against Rheumatism suggests ACE inhibitors or angiotensin receptor blockers for patients with proteinuria or hypertension 2
Statins are recommended for patients with persistent dyslipidemia (target LDL-cholesterol <100 mg/dl) by the European League Against Rheumatism 2

The American College of Rheumatology recommends scheduling visits every 2-4 weeks for the first 2-4 months after diagnosis or flare 2
Monitoring weight, blood pressure, serum creatinine, eGFR, serum albumin, proteinuria, urinary sediment, C3/C4, anti-dsDNA antibodies, and complete blood count is suggested by the European League Against Rheumatism 2
Expect at least 25% reduction in proteinuria by 3 months and 50% by 6 months, according to the American College of Rheumatology 3

The European League Against Rheumatism recommends continuing treatment with either mycophenolic acid analogs at lower doses (initial target 2 g/day) or azathioprine (2 mg/kg/day) for patients improving after initial treatment 2
Maintaining treatment for at least 3 years is suggested by the American College of Rheumatology 2

The American College of Rheumatology recommends switching from mycophenolic acid analogs to cyclophosphamide or vice versa for patients failing to improve within 3-4 months or not achieving partial response after 6-12 months 2, 5
Considering rituximab as add-on treatment or monotherapy is suggested by the European League Against Rheumatism 2, 5
Calcineurin inhibitors (especially for class V nephritis) are recommended by the American College of Rheumatology 2, 5