What is the role of Rituximab (rituximab) in the treatment of IgA (Immunoglobulin A) nephropathy?

Role of Rituximab in IgA Nephropathy Treatment

Rituximab is not recommended as a first-line therapy for IgA nephropathy but may be considered in specific cases of severe or refractory disease when conventional therapies have failed.

Current Treatment Guidelines for IgA Nephropathy

The management of IgA nephropathy (IgAN) should follow a stepwise approach:

First-Line Management

• Optimized supportive care is the primary focus, including:
  • RAS blockade (ACE inhibitors or ARBs) for all patients with proteinuria >0.5 g/day 1
  • Blood pressure control
  • Cardiovascular risk reduction
  • Lifestyle modifications (diet, smoking cessation, weight control, exercise)

Second-Line Therapy

If proteinuria remains >0.75-1 g/day despite at least 90 days of optimized supportive care, consider immunosuppressive therapy:

• Corticosteroids are the most established immunosuppressive option
• Mycophenolate mofetil (MMF) may be considered in specific populations

Evidence for Rituximab in IgA Nephropathy

The 2021 KDIGO guidelines for glomerular diseases do not specifically recommend rituximab for IgA nephropathy 1. The guidelines focus primarily on supportive care, corticosteroids, and other immunosuppressants.

Limited evidence exists for rituximab in IgA nephropathy:

1. Case Reports and Small Studies:

   • A small prospective trial of single-dose rituximab in primary glomerular diseases showed CD19 and CD20 cell depletion in IgA nephropathy patients but no significant reduction in proteinuria at 6 months 2
   • A case series of four adult patients with severe IgA nephropathy or IgA vasculitis with nephritis treated with rituximab showed improved renal function and reduced albuminuria after 17-22 months 3

2. Transplant Setting:

   • In kidney transplant recipients with recurrent IgA nephropathy, rituximab-based regimens showed promising results with decreased proteinuria and maintained renal allograft function compared to conventional therapy 4

Potential Role for Rituximab in IgA Nephropathy

Based on the available evidence, rituximab may be considered in:

1. Severe, refractory cases that have failed conventional therapy
2. Recurrent IgA nephropathy post-transplant with severe activity
3. IgA vasculitis with nephritis presenting with nephritic-nephrotic syndrome

Practical Considerations for Rituximab Use

If rituximab is considered:

• Dosing: Common regimens include 375 mg/m² weekly for 4 weeks or two doses of 1000 mg given 2 weeks apart 5
• Monitoring:
  • Complete blood count with differential every 2-4 months during treatment
  • Immunoglobulin levels (IgG, IgM, IgA) every 6 months
  • Hepatitis B screening before initiation (HBsAg, Anti-HBc, HBV DNA if either test is positive)

Limitations and Cautions

• The evidence supporting rituximab in IgA nephropathy is limited to small case series and observational studies
• No randomized controlled trials have established its efficacy specifically for IgA nephropathy
• Risk of infections and other adverse events must be considered
• Cost-effectiveness has not been established for IgA nephropathy

Conclusion

While rituximab has shown efficacy in various glomerular diseases, its role in IgA nephropathy remains limited. Current guidelines do not recommend it as a first-line therapy. Optimized supportive care with RAS blockade remains the cornerstone of management, with corticosteroids considered for patients with persistent proteinuria despite optimal supportive care. Rituximab should be reserved for severe, refractory cases or specific clinical scenarios like post-transplant recurrence with severe activity.