Is Mycophenolate Mofetil (MMF) used in the treatment of IgA nephropathy?

Mycophenolate Mofetil in IgA Nephropathy

Mycophenolate mofetil (MMF) is not recommended for most patients with IgA nephropathy, except in Chinese patients where it may be used as a glucocorticoid-sparing agent. 1

Geographic Considerations in MMF Use

Chinese Patients

• MMF may be beneficial in Chinese patients with IgA nephropathy:
  • Can be used as a glucocorticoid-sparing agent 1
  • Studies in Chinese populations have shown promising results:
    • In a long-term study following Chinese patients for 6 years, MMF treatment resulted in fewer patients reaching the composite endpoint of serum creatinine doubling or ESRD (3 vs 10 in control group) 2
    • Significantly less decline in estimated GFR in MMF-treated Chinese patients 2

Non-Chinese Patients

• MMF is not recommended for non-Chinese patients with IgA nephropathy 1
• This recommendation is based on differences in treatment response observed between ethnic populations

Evidence Quality and Considerations

The recommendation against MMF use in non-Chinese patients is supported by systematic reviews showing:

• Inconsistent results across studies 3
• No significant difference in therapeutic effect compared to other therapies in mixed populations 3
• No significant effects on reducing proteinuria or protecting renal function in general populations 3

However, subgroup analysis suggests that shorter-term therapy (<18 months) might be more beneficial than longer-term use 3.

Current Standard of Care for IgA Nephropathy

The standard approach to IgA nephropathy management includes:

1. Optimized supportive care for at least 90 days before considering immunosuppression 4:

   • Maximizing RAS blockade with ACEi or ARB
   • Strict BP control (<130/80 mmHg for proteinuria <1g/day; <125/75 mmHg for proteinuria >1g/day)
   • Lifestyle modifications

2. For persistent proteinuria >1g/day despite optimized supportive care:

   • Consider glucocorticoids if eGFR ≥30 ml/min/1.73m² 4
   • Consider SGLT2 inhibitors to reduce CKD progression 4

Special Situations

• Rapidly progressive IgA nephropathy: Consider cyclophosphamide and glucocorticoids if extensive crescent formation (>50% of glomeruli) 1
• IgA with minimal change disease: Treat according to minimal change disease guidelines 1
• Japanese patients: Consider tonsillectomy 1

Potential Risks of MMF

When considering MMF in Chinese patients, be aware of potential side effects:

• Gastrointestinal issues (diarrhea, nausea)
• Increased risk of infections
• Hematologic abnormalities

Emerging Therapies

Several newer therapies are being evaluated for IgA nephropathy 1, 4:

• SGLT2 inhibitors
• Sparsentan
• Atrasentan
• Hydroxychloroquine
• Enteric-coated budesonide
• Complement inhibitors
• B-cell targeted therapies

Conclusion

While MMF shows promise in Chinese patients with IgA nephropathy, current guidelines do not support its use in non-Chinese populations. Treatment decisions should be guided by patient ethnicity, disease severity, and response to supportive care measures.