Initial Treatment for Lupus Nephritis
For patients with active Class III or IV lupus nephritis, initial treatment should include glucocorticoids plus mycophenolic acid analogs (MPAA), low-dose intravenous cyclophosphamide, belimumab with either MPAA or cyclophosphamide, or MPAA with a calcineurin inhibitor when kidney function is not severely impaired. 1
First-Line Treatment Options
Medication Regimens
- Glucocorticoids plus one of the following:
- Mycophenolic acid analogs (MPAA) - preferred first-line option
- Low-dose intravenous cyclophosphamide (total dose 3g over 3 months)
- Belimumab combined with either MPAA or low-dose cyclophosphamide
- MPAA with calcineurin inhibitor (when eGFR >45 ml/min per 1.73 m²)
Glucocorticoid Regimen
- Initial therapy: Consider methylprednisolone IV pulses (0.25-0.5 g/day for up to 3 days)
- Followed by oral prednisone: 0.5-0.6 mg/kg/day (maximum 40 mg) with gradual tapering
- A reduced-dose glucocorticoid regimen is recommended to minimize adverse effects while maintaining efficacy 1
Treatment Selection Based on Lupus Nephritis Class
Class III/IV Lupus Nephritis
- MPAA (mycophenolate mofetil 1-2 g/day or mycophenolic acid 720-1440 mg/day) with glucocorticoids 1
- Low-dose IV cyclophosphamide may be preferred in Caucasian patients due to better efficacy/toxicity ratio 1
- MPAA may have greater efficacy in patients of African descent 1
Class V Lupus Nephritis (Membranous)
- MPAA with glucocorticoids is recommended for most cases with nephrotic-range proteinuria 1
- Intravenous cyclophosphamide (6 bimonthly pulses 0.5-1 g/m²) with glucocorticoids is an alternative 1
Class II Lupus Nephritis with Significant Proteinuria
- Low-to-moderate doses of glucocorticoids (prednisone 0.25-0.5 mg/kg/day) alone or with azathioprine (1-2 mg/kg/day) as a steroid-sparing agent 1
Adjunctive Therapies
- Hydroxychloroquine: Should be co-administered at a dose not exceeding 5 mg/kg/day (adjusted for GFR) 2
- RAAS blockade: ACE inhibitors or ARBs for all patients with proteinuria >500 mg/g 2
- Infection prophylaxis: Consider Pneumocystis jirovecii prophylaxis 1
- Bone protection: Calcium and vitamin D supplementation 1, 2
- Thrombosis prevention: Consider low-dose aspirin, especially with antiphospholipid antibodies 1, 2
Monitoring Treatment Response
Treatment Targets
- 25% reduction in proteinuria by 3 months
- 50% reduction by 6 months
- UPCR target below 500-700 mg/g by 12 months 2
Follow-up Schedule
- Initial visits every 2-4 weeks, then adjust based on response
- Monitor for:
- Renal function and proteinuria
- Complement levels and anti-dsDNA antibody titers
- Medication side effects
- Infections and other complications
Special Considerations
- Reduced-dose MPAA: Asian patients may respond to lower doses (0.5-1 g/day) of MMF with fewer side effects 3
- Severe disease: High-dose intravenous cyclophosphamide may be more appropriate for patients with severely impaired renal function (GFR 25-80 ml/min) or with crescents/necrosis in >25% of glomeruli 1
- Fertility concerns: Minimize cyclophosphamide exposure in women at risk for amenorrhea/infertility or men planning to father children 1
Common Pitfalls and Caveats
- Medication adherence: Poor adherence is a common cause of treatment failure 2
- Infection risk: Assess for tuberculosis, hepatitis B/C, and HIV before starting immunosuppression 1
- Cumulative cyclophosphamide: Minimize lifetime exposure to <36g to reduce cancer risk 1
- UV light exposure: Recommend broad-spectrum sunscreen and limited UV exposure 1
- Pregnancy planning: Provide contraception counseling as unplanned pregnancy during active treatment can be problematic 1
While recent research suggests higher initial prednisone doses may achieve better complete renal response rates 4, the KDIGO 2024 guidelines recommend reduced-dose regimens to minimize long-term glucocorticoid toxicity while maintaining efficacy 1.