What is the treatment approach for Systemic Lupus Erythematosus (SLE) patients with Chronic Kidney Disease (CKD)?

From the Guidelines

The treatment approach for Systemic Lupus Erythematosus (SLE) patients with Chronic Kidney Disease (CKD) should prioritize a multifaceted strategy targeting both disease processes, with initial therapy including corticosteroids and immunosuppressive agents, such as mycophenolate mofetil (MMF) or cyclophosphamide, as recommended by the most recent guidelines 1.

Key Components of Treatment

• Initial therapy: corticosteroids (prednisone 0.5-1 mg/kg/day) combined with immunosuppressive agents, such as MMF (2-3g/day) or cyclophosphamide (500-1000 mg/m² monthly for 6 months) 1
• Maintenance therapy: lower-dose MMF (1-2g/day) or azathioprine (1-2.5 mg/kg/day) 1
• Hydroxychloroquine (200-400mg daily) should be continued in all SLE patients unless contraindicated 1
• Blood pressure control: ACE inhibitors or ARBs as preferred agents targeting <130/80 mmHg 1
• Renal protective measures: strict glycemic control in diabetic patients, smoking cessation, and avoiding nephrotoxic medications 1

Monitoring and Adjustments

• Regular monitoring of renal function, proteinuria, and SLE disease activity is essential, with adjustments to medication dosing based on GFR 1
• Advanced CKD may require renal replacement therapy, with transplantation offering better outcomes than dialysis when feasible 1

Management of Unsatisfactory Response

• Verify adherence to treatment and ensure adequate dosing of immunosuppressive medications 1
• Consider switching to an alternative recommended treatment regimen when there is persistent active disease 1
• Consider the addition of rituximab or other biologic therapies in patients refractory to initial treatment 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).

The treatment approach for Systemic Lupus Erythematosus (SLE) patients with Chronic Kidney Disease (CKD), specifically those with lupus nephritis, involves the use of belimumab (BENLYSTA) 10 mg/kg administered intravenously plus standard therapy. The standard therapy includes corticosteroids with mycophenolate or cyclophosphamide for induction, followed by mycophenolate or azathioprine for maintenance.

• Key components of treatment:
  • Belimumab 10 mg/kg intravenous administration
  • Standard therapy with corticosteroids and immunosuppressants
• Goals of treatment:
  • Achieve Primary Efficacy Renal Response (PERR) at Week 104
  • Reduce urine protein:creatinine ratio and improve estimated glomerular filtration rate (eGFR)
  • Minimize renal-related events or death 2

From the Research

Treatment Approach for SLE Patients with CKD

The treatment approach for Systemic Lupus Erythematosus (SLE) patients with Chronic Kidney Disease (CKD) involves the use of immunosuppressive agents to manage lupus nephritis. Some key points to consider:

• The optimal treatment of severe lupus nephritis is unclear, but regimens consisting of steroid and cyclophosphamide (CYC) appear to be most effective 3.
• Mycophenolate mofetil (MMF) is a new immunosuppressive agent that has shown efficacy in patients with lupus nephritis, particularly those who are refractory to CYC treatment or have significant toxicity 3, 4.
• Glucocorticoids (GCs) are one of the most effective first-line treatments for SLE, but their use is associated with damage, and recent guidelines recommend a more accurate approach to their use, including lower starting doses and rapid tapering schemes 5.

Immunosuppressive Agents

Some immunosuppressive agents used in the treatment of SLE patients with CKD include:

• Mycophenolate mofetil (MMF): has shown efficacy in patients with lupus nephritis, particularly those with proliferative forms of nephritis 3, 4, 6.
• Azathioprine (AZA): has been compared to MMF in the maintenance therapy of lupus nephritis, and both agents have shown similar efficacy 6.
• Rituximab (RTX): has been used in combination with hydroxychloroquine, prednisone, and low doses of MMF to treat active SLE, and has shown effectiveness in reducing disease activity 7.

Treatment Outcomes

Treatment outcomes for SLE patients with CKD have been evaluated in several studies:

• MMF treatment has been shown to improve renal function and reduce proteinuria in patients with lupus nephritis 3, 4, 6.
• The combination of RTX, hydroxychloroquine, prednisone, and low doses of MMF has been shown to be effective in reducing disease activity and achieving remission in patients with active SLE 7.
• Both MMF and AZA have been shown to be effective as maintenance therapy for lupus nephritis, with similar rates of remission and relapse 6.