What is the diagnosis and treatment of Systemic Lupus Erythematosus (SLE) related kidney inflammation, also known as Lupus nephritis?

From the Guidelines

Lupus nephritis should be treated with a target of complete response, defined as proteinuria <0.5–0.7 g/24 hours with (near-) normal glomerular filtration rate, by 12 months, using initial induction treatment with mycophenolate mofetil (MMF 2–3 g/day) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids. The treatment approach for lupus nephritis depends on the severity and class of nephritis, with active proliferative LN requiring aggressive therapy 1. Initial treatment typically consists of induction therapy with high-dose corticosteroids combined with either MMF or CY, with MMF being a preferred option due to its efficacy and lower side effects 1.

Some key points to consider in the management of lupus nephritis include:

• The use of hydroxychloroquine with regular ophthalmological monitoring 1
• The importance of blood pressure control, preferably with ACE inhibitors or ARBs to reduce proteinuria 1
• Regular monitoring of kidney function tests, urinalysis, complement levels, and anti-dsDNA antibodies every 3-6 months 1
• The consideration of MMF/CNI combination and high-dose CY as alternatives for patients with nephrotic-range proteinuria and adverse prognostic factors 1
• The recommendation for subsequent long-term maintenance treatment with MMF or azathioprine, with no or low-dose glucocorticoids 1

In non-responding disease, switching of induction regimens or the use of rituximab may be necessary 1. Additionally, assessment for kidney and extra-renal disease activity, and management of comorbidities is crucial in the management of lupus nephritis 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 (BENLYSTA) is effective in treating lupus nephritis.
• The primary efficacy endpoint, Primary Efficacy Renal Response (PERR) at Week 104, was achieved by 43% of patients receiving BENLYSTA 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 significant improvements in renal response and complete renal response compared to placebo 2.
• Key benefits of belimumab in lupus nephritis treatment include:
  • Improved Primary Efficacy Renal Response (PERR) at Week 104
  • Improved Complete Renal Response (CRR) at Week 104
  • Improved PERR at Week 52

From the Research

Treatment Options for Lupus Nephritis

• Mycophenolate mofetil (MMF) has been shown to be effective in treating lupus nephritis, with studies 3, 4, 5, 6 demonstrating its efficacy in inducing remission and reducing proteinuria.
• MMF has been compared to cyclophosphamide in several studies, with results suggesting that MMF is at least as effective as cyclophosphamide in inducing remission 3, 4.
• The 2024 APLAR Consensus on the Management of Lupus Nephritis recommends a combination of glucocorticoids with cyclophosphamide, mycophenolate mofetil, or calcineurin inhibitors as first-line options for initial treatment of lupus nephritis 7.
• MMF has also been shown to be a useful treatment for patients who have failed, are intolerant of, or have relapsed after treatment with steroids and cyclophosphamide 5.

Comparison of Treatment Outcomes

• A study published in 2005 found that MMF was more effective than intravenous cyclophosphicide in inducing remission of lupus nephritis, with an absolute difference of 16.7 percentage points in complete remission rates 3.
• Another study published in 2015 found that MMF was non-inferior to cyclophosphamide for induction therapy and superior to azathioprine as maintenance therapy 6.
• A study published in 2007 found that MMF was effective in reducing proteinuria and improving serum albumin and complement fractions in patients with lupus nephritis who had failed or were intolerant of steroids and cyclophosphamide 5.

Safety Profile and Side Effects

• MMF has been shown to-desktop have a more favorable safety profile compared to cyclophosphamide, with fewer severe infections and hospitalizations 3.
• However, MMF has been associated with more diarrhea compared to cyclophosphamide 3, 4.
• A study published in 2007 found that MMF was well-tolerated, with only one patient requiring discontinuation of treatment due to side effects 5.