What is the diagnosis and treatment of lupus (Systemic Lupus Erythematosus) nephritis?

From the Guidelines

Lupus nephritis should be treated with induction therapy using mycophenolate mofetil (MMF 2–3 g/day) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), combined with glucocorticoids, to achieve complete response by 12 months. The treatment approach depends on the disease severity and the presence of nephrotic-range proteinuria or adverse prognostic factors 1.

Key Considerations

• The target of therapy is complete response, defined as proteinuria <0.5–0.7 g/24 hours with (near-) normal glomerular filtration rate, which can be extended in patients with baseline nephrotic-range proteinuria 1.
• Hydroxychloroquine is recommended with regular ophthalmological monitoring 1.
• For patients with nephrotic-range proteinuria and adverse prognostic factors, MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives 1.
• Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids 1.

Monitoring and Management

• Regular monitoring includes kidney function tests, urinalysis, complement levels, and anti-dsDNA antibodies every 3-6 months.
• Blood pressure control is essential, preferably with ACE inhibitors or ARBs to reduce proteinuria.
• Patients should be aware of infection risks while immunosuppressed and report fever or worsening symptoms promptly.

Special Considerations

• In non-responding disease, switch of induction regimens or rituximab are recommended 1.
• In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin–angiotensin–aldosterone blockade, MMF in combination with glucocorticoids is preferred 1.

From the FDA Drug Label

The safety and effectiveness of BENLYSTA 10 mg/kg administered intravenously over 1 hour on Days 0,14,28, and then every 28 days plus standard therapy were evaluated in a 104-week, randomized, double‑blind, placebo‑controlled trial in 448 patients with active proliferative and/or membranous lupus nephritis (Trial 5) The primary efficacy endpoint was Primary Efficacy Renal Response (PERR) at Week 104, defined as a response at Week 100 confirmed by a repeat measurement at Week 104 of the following parameters: urine protein:creatinine ratio (uPCR) ≤0.7 g/g and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1. 73 m2 or no decrease in eGFR of >20% from pre-flare value. The proportion of patients achieving PERR at Week 104 was significantly higher in patients receiving BENLYSTA plus standard therapy compared with placebo plus standard therapy (Table 7).

Lupus Nephritis Treatment with Belimumab:

• The drug label provides evidence that belimumab is effective in treating lupus nephritis.
• The primary efficacy endpoint, Primary Efficacy Renal Response (PERR), was achieved by 43% of patients receiving belimumab plus standard therapy, compared to 32% of patients receiving placebo plus standard therapy.
• The results suggest that belimumab can be used to treat lupus nephritis, with a significant improvement in renal response compared to placebo 2.
• Key benefits of belimumab in lupus nephritis treatment include:
  • Improved renal response
  • Reduced proteinuria
  • Improved estimated glomerular filtration rate (eGFR)

From the Research

Treatment Options for Lupus Nephritis

• The treatment of lupus nephritis (LN) often involves the use of immunosuppressive agents, with various regimens having been developed and studied for their efficacy and safety 3, 4, 5, 6, 7.
• Mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC) are two commonly used immunosuppressive agents for the induction therapy of LN, with MMF having been shown to be more effective in inducing remission and having a more favorable safety profile than CYC 3, 5.
• The APLAR consensus recommends a combination of glucocorticoids with CYC, MMF, or calcineurin inhibitors as first-line options for the initial treatment of LN, with an upfront combination of immunosuppressive drugs and biological agents considered in patients at significant risk of disease progression and renal function deterioration 4.
• Belimumab and voclosporin are two recently approved combinatory treatments that have shown promise in improving disease outcomes and enabling faster steroid tapering, although it remains uncertain whether these dual regimens should become the first-line choice for all patients or be prioritized to certain subgroups 6.

Efficacy and Safety of Immunosuppressive Agents

• A systematic review and network meta-analysis compared the efficacy and safety of various immunosuppressive regimens in adults with LN, finding that the combination of tacrolimus, MMF, and glucocorticoid provided the best result for total remission rate and SLEDAI, while the combination of voclosporin, MMF, and glucocorticoid gave the best improvement in complete remission rate 7.
• The same study found that the combination of CYC, MMF, and glucocorticoid was associated with the lowest risk of relapse and cancer, while the combination of obinutuzumab, MMF, and glucocorticoid was associated with the lowest risk of all-cause mortality 7.
• Rituximab plus MMF plus glucocorticoid was associated with the lowest risk of end-stage renal disease, while the risk of infection was lowest in patients treated with azathioprine plus CYC plus glucocorticoid 7.

Real-World Evidence

• A real-world study compared the effectiveness and safety of MMF and CYC in LN induction therapy, finding that MMF was at least equivalent to CYC, with superior tolerance 5.
• The study found that the cumulative proportion of total renal remission in 6 months and complete renal remission in 12 months were significantly higher in the MMF group than in the CYC group, with MMF use being the only predictor of complete renal remission 5.