From the Guidelines
Treatment of lupus nephritis class IV (stage 4) with impaired renal function requires aggressive immunosuppressive therapy with a two-phase approach: induction followed by maintenance, using glucocorticoids plus mycophenolic acid analogs (MPAA) or low-dose intravenous cyclophosphamide, as recommended by the most recent KDIGO 2024 clinical practice guideline 1.
Induction Therapy
The standard regimen for induction combines high-dose corticosteroids (typically prednisone 0.5-1 mg/kg/day, maximum 60 mg daily) with either cyclophosphamide or mycophenolate mofetil (MMF) 1.
- Cyclophosphamide can be given as IV pulses (500-1000 mg/m² monthly for 6 months) or in the Euro-Lupus regimen (500 mg IV every 2 weeks for 6 doses).
- Alternatively, MMF 2-3 g/day divided into two doses is equally effective and often preferred due to fewer side effects, particularly for women concerned about fertility.
Maintenance Therapy
After 3-6 months of induction therapy, maintenance treatment follows with lower-dose prednisone (tapered to 5-7.5 mg/day) plus either MMF (1-2 g/day) or azathioprine (1.5-2.5 mg/kg/day) for at least 3 years 1.
- Hydroxychloroquine (5 mg/kg/day, maximum 400 mg daily) should be continued indefinitely.
Supportive Care
Supportive care includes:
- Blood pressure control (target <130/80 mmHg) with ACE inhibitors or ARBs, which help reduce proteinuria and protect kidney function.
- Regular monitoring of kidney function, urinary protein, blood counts, and drug levels is essential to assess response and adjust therapy. This aggressive approach is necessary because class IV lupus nephritis represents diffuse proliferative disease affecting more than 50% of glomeruli, carrying the highest risk of progression to end-stage kidney disease if left untreated 1.
From the Research
Treatment for Lupus Nephritis Stage 4
The treatment for Lupus Nephritis (Systemic Lupus Erythematosus - SLE) stage 4, characterized by impaired renal function, involves the use of immunosuppressive agents.
- Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been compared with cyclophosphamide in trials for lupus nephritis 2.
- MMF has been associated with a reduced risk of infection and amenorrhea, although this finding is not universal 2.
- A subgroup analysis of patients with low estimated glomerular filtration rates (eGFRs) from the Aspreva Lupus Management Study found that MMF may result in quicker recovery of kidney function compared with those treated with cyclophosphamide 3.
Comparison of Treatment Regimens
- A pooled analysis of randomized controlled trials found that there was no significant difference in 12-month renal responses between patients receiving low-dose prednisone following intravenous GC compared with those receiving initial high doses 4.
- The analysis also found that serious adverse events were less frequent in patients receiving low-dose initial GC 4.
- A retrospective propensity analysis of data from two large active lupus nephritis controlled trials suggested that a lower dose regimen of MMF and steroids may result in better long-term safety without compromising efficacy 5.
Efficacy of Mycophenolate Mofetil
- A study found that MMF appears to be an efficacious and safe treatment in patients with proliferative forms of lupus nephritis who do not respond to or cannot tolerate conventional treatment 6.
- The study also found that MMF demonstrated a steroid-sparing effect in the whole population 6.
- However, the efficacy of MMF in lupus membranous nephropathy remains unclear 6.