What is the initial treatment for lupus nephritis?

From the Guidelines

The initial treatment for lupus nephritis should involve a combination of glucocorticoids and immunosuppressive medications, with mycophenolic acid analogs (MPAA) or low-dose intravenous cyclophosphamide being recommended as the first-line treatment options, as stated in the most recent guideline from Kidney International (2024) 1.

Key Considerations

• The treatment goal is to achieve complete response, defined as proteinuria <0.5–0.7 g/24 hours with (near-) normal glomerular filtration rate, by 12 months 1.
• Glucocorticoids, such as pulses of intravenous methylprednisolone, followed by oral prednisone (0.3–0.5 mg/kg/day), are used to rapidly control inflammation 1.
• Immunossuppressive agents, including mycophenolate mofetil (MMF, 2-3 g/day) or cyclophosphamide (either as monthly intravenous pulses of 0.5-1 g/m² for 6 months or lower-dose regimens), are added to the treatment regimen for induction therapy 1.
• The choice of agent depends on the initial regimen and plans for pregnancy, with MMF or azathioprine being preferred for maintenance therapy 1.

Treatment Options

• Mycophenolic acid analogs (MPAA) are recommended as a first-line treatment option, with a dose of 1-2 g/day divided into two doses 1.
• Low-dose intravenous cyclophosphamide is also recommended, with a dose of 500 mg × 6 biweekly doses 1.
• Belimumab and either MPAA or low-dose intravenous cyclophosphamide may be considered as alternative treatment options 1.
• MPAA and a calcineurin inhibitor (CNI) may be used when kidney function is not severely impaired (i.e., estimated glomerular filtration rate [eGFR] ≤ 45 ml/min per 1.73 m²) 1.

Monitoring and Supportive Care

• Regular monitoring of kidney function, urine protein levels, and lupus disease activity is essential to assess treatment response and adjust therapy accordingly 1.
• Supportive care includes blood pressure control with ACE inhibitors or ARBs, which help reduce proteinuria and protect kidney function 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 patients had a clinical diagnosis of SLE according to American College of Rheumatology classification criteria; biopsy-proven lupus nephritis Class III, IV, and/or V; and had active renal disease at screening requiring standard therapy: corticosteroids with 1) mycophenolate for induction followed by mycophenolate for maintenance, or 2) cyclophosphamide for induction followed by azathioprine for maintenance.

The initial treatment for lupus nephritis includes:

• Corticosteroids
• Mycophenolate for induction followed by mycophenolate for maintenance
• Cyclophosphamide for induction followed by azathioprine for maintenance 2

From the Research

Initial Treatment for Lupus Nephritis

The initial treatment for lupus nephritis typically involves a combination of immunosuppressive drugs and glucocorticoids.

• According to the 2024 APLAR Consensus on the Management of Lupus Nephritis 3, the recommended initial treatment options include:
  • Glucocorticoids (GCs) with cyclophosphamide (CYC)
  • Glucocorticoids (GCs) with mycophenolate mofetil (MMF)
  • Glucocorticoids (GCs) with calcineurin inhibitors (CNIs)
• The use of rituximab as an induction therapy for lupus nephritis has also been studied, with some studies showing promising results 4, 5.
• A study published in 2009 found that rituximab induction therapy and MMF maintenance therapy were effective in treating lupus nephritis, allowing for a reduction or total withdrawal of corticosteroids 4.
• Another study published in 2020 found that rituximab use as induction therapy for lupus nephritis resulted in complete renal response (CRR) or partial renal response (PRR) in 66% of patients 5.
• The optimal dose of prednisone for the treatment of lupus nephritis is still a topic of debate, with some studies suggesting that medium doses of prednisone may be as effective as high doses while causing less toxicity 6.

Factors Influencing Treatment

The treatment of lupus nephritis can be influenced by several factors, including:

• The severity of the disease
• The presence of co-morbidities
• The patient's response to previous treatments
• The potential side effects of immunosuppressive drugs and glucocorticoids
• The need for adjunctive therapies, such as hydroxychloroquine, to manage related co-morbidities 3, 7, 6.