For an adult with biopsy‑proven immunoglobulin A (IgA) nephropathy and progressive disease (proteinuria ≥ 1 g/day, estimated glomerular filtration rate 30‑60 mL/min/1.73 m², and active proliferative lesions), is treatment with mycophenolate mofetil plus methylprednisolone appropriate as first‑line therapy?

MMF Plus Methylprednisolone for IgA Nephropathy

Mycophenolate mofetil (MMF) plus methylprednisolone is NOT recommended as first-line therapy for IgA nephropathy in non-Chinese patients, regardless of disease severity or histologic features. 1

Guideline-Based Treatment Algorithm

Step 1: Optimize Supportive Care First (Mandatory 90-Day Trial)

Before any immunosuppression is considered, all patients must receive at least 90 days of maximally optimized supportive care: 1, 2

• ACE-inhibitor or ARB titrated to the highest tolerated dose when proteinuria >0.5 g/day, regardless of blood pressure 1
• **Blood pressure target <125/75 mmHg** for proteinuria >1 g/day 2
• Dietary sodium restriction to <2.0 g/day 2
• SGLT2 inhibitor (dapagliflozin or empagliflozin) added to RAS blockade 2

Step 2: Reassess After 90 Days

If proteinuria remains >0.75–1 g/day after 90 days of optimized supportive care AND eGFR is ≥30 mL/min/1.73 m², the patient is high-risk and may be considered for immunosuppression. 1

Step 3: Immunosuppressive Options (in Order of Preference)

First choice: Glucocorticoid monotherapy 1

• Intravenous methylprednisolone 1 g daily for 3 days at months 1,3, and 5, PLUS
• Oral prednisone 0.8–1 mg/kg/day for 2 months, then taper over 4 months 2
• This regimen achieved 97% 10-year renal survival versus 53% without immunosuppression 2

Second choice: Clinical trial enrollment (preferred over off-guideline regimens) 1

MMF is explicitly NOT recommended in non-Chinese patients 1

Why MMF Plus Methylprednisolone Is Not Recommended

The KDIGO 2021 guidelines state unequivocally that "the use of mycophenolate mofetil (MMF) in IgAN is not recommended in non-Chinese patients" and that "other immunosuppressive therapies are not recommended in IgAN, including azathioprine, cyclophosphamide (except in the setting of rapidly progressive IgAN), calcineurin inhibitors (CNIs), and rituximab." 1

Evidence Limitations for MMF

Although several Chinese studies suggest benefit from MMF combined with corticosteroids 3, 4, 5, 6, these findings have not been replicated in non-Chinese populations. 7 A systematic review found that in moderately-advanced IgAN, MMF showed no benefit and possibly worse outcomes; only in highly selected patients with less advanced disease was there any proteinuria reduction. 7

The Chinese Exception

MMF may be used as a glucocorticoid-sparing agent ONLY in Chinese patients. 1, 8 This population-specific recommendation reflects genetic, environmental, or disease-phenotype differences that have not been validated elsewhere.

Absolute Contraindications to Any Glucocorticoid Therapy

Even glucocorticoid monotherapy should be avoided entirely or used with extreme caution in patients with: 1, 9

• eGFR <30 mL/min/1.73 m²
• Diabetes mellitus
• Obesity (BMI >30 kg/m²)
• Latent infections (tuberculosis, hepatitis B/C, HIV)
• Active peptic ulceration
• Uncontrolled psychiatric disease
• Severe osteoporosis

Your patient has eGFR 30–60 mL/min/1.73 m², which places them in a gray zone where adverse treatment effects are more likely. 1

Special Scenario: Rapidly Progressive IgAN

If your patient has >50% crescents on biopsy PLUS rapidly progressive renal decline (not merely the presence of active proliferative lesions), then the diagnosis is crescentic IgAN and treatment consists of cyclophosphamide plus glucocorticoids using an ANCA-vasculitis protocol—NOT MMF. 1

The presence of "active proliferative lesions" alone does not constitute rapidly progressive IgAN and does not justify deviation from standard guidelines. 1

Critical Pitfalls to Avoid

• Do not initiate any immunosuppression before completing ≥90 days of maximally optimized supportive care including SGLT2 inhibitor 2
• Do not use MMF unless the patient is ethnically Chinese 1
• Do not combine MMF with methylprednisolone as first-line therapy in any population; even in Chinese patients, MMF is used as a glucocorticoid-sparing agent, not in combination 1
• Do not rely on histologic features (MEST-C score, crescent count, proliferative lesions) to justify off-guideline immunosuppression; these features predict prognosis but do not determine treatment choice 1, 2

Recommended Approach for Your Patient

1. Maximize supportive care for 90 days: uptitrate ACE-inhibitor/ARB, add SGLT2 inhibitor, achieve BP <125/75 mmHg, restrict sodium 2
2. Reassess proteinuria at 90 days 1
3. If proteinuria remains >1 g/day and eGFR ≥30 mL/min/1.73 m², offer glucocorticoid monotherapy (methylprednisolone pulses plus oral prednisone taper) OR enroll in a clinical trial 1, 2
4. Do not use MMF unless the patient is Chinese, and even then only as a glucocorticoid-sparing alternative, not in combination 1