When is the Pozzi regimen used in patients with IgA (Immunoglobulin A) nephropathy?

When to Use the Pozzi Regimen in IgA Nephropathy

The Pozzi regimen should be used in patients with IgA nephropathy who have persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care (maximally tolerated ACE inhibitor or ARB plus blood pressure control), and who have preserved kidney function with eGFR >50 ml/min per 1.73 m² 1.

Patient Selection Criteria

The Pozzi protocol is indicated when ALL of the following criteria are met:

• Proteinuria ≥1 g/day that persists after at least 90 days of maximal supportive therapy 1
• eGFR >50 ml/min per 1.73 m² at the time immunosuppression is being considered 1
• Optimized supportive care has been maximized, including:
  • ACE inhibitor or ARB titrated to maximally tolerated doses 1, 2
  • Blood pressure controlled to <125/75 mmHg (for proteinuria >1 g/day) 1
  • Sodium restriction and cardiovascular risk factor modification 2, 3

The Pozzi Regimen Protocol

The regimen consists of two components administered over 6 months 1:

• Intravenous methylprednisolone: 1 gram daily for 3 consecutive days at the beginning of months 1,3, and 5 1, 4
• Oral prednisone: 0.5 mg/kg on alternate days for the entire 6-month period 1, 4

This protocol demonstrated long-term benefit with 10-year renal survival of 97% versus 53% in untreated controls in the original Italian trial 1.

Absolute Contraindications to the Pozzi Regimen

Do NOT use the Pozzi regimen in patients with:

• eGFR <30 ml/min per 1.73 m² (unless rapidly progressive crescentic disease) 1
• Uncontrolled diabetes or metabolic syndrome due to increased risk of serious infections and metabolic complications 1, 3
• Advanced age with frailty 1
• Obesity (increased toxicity risk) 1
• Latent infections including tuberculosis, HIV, hepatitis B or C 1
• Crescentic IgAN with >50% crescents (requires cyclophosphamide plus steroids instead) 1

Special Populations and Alternative Approaches

For Chinese patients: Consider mycophenolate mofetil as a glucocorticoid-sparing alternative if steroids are contraindicated 1, 3

For Japanese patients: Tonsillectomy may be considered as an alternative approach, though this is not recommended in non-Japanese populations 1

For patients with eGFR 30-50 ml/min per 1.73 m²: The risk-benefit ratio of corticosteroids becomes less favorable; maximal supportive care alone may be preferred 1, 2

Critical Pitfalls to Avoid

• Never initiate the Pozzi regimen without first optimizing supportive care for at least 3 months 1, 2
• Do not use corticosteroids combined with cyclophosphamide or azathioprine in standard IgAN (only for crescentic disease) 1
• Avoid immunosuppression in patients with advanced CKD (eGFR <30 ml/min per 1.73 m²) as toxicity outweighs benefit 1, 2
• Do not overlook serious adverse event risk stratification before initiating therapy, particularly infection risk and metabolic complications 1, 3

Treatment Goals and Monitoring

The primary goal is proteinuria reduction to <1 g/day, which serves as a surrogate marker for improved kidney outcomes 1, 2. Monitor:

• Proteinuria every 3 months during and after treatment 3
• eGFR every 3-6 months to assess kidney function trajectory 3
• Adverse effects including infections, glucose intolerance, and weight gain 1, 5

The Pozzi regimen achieved full clinical remission in 20% of patients versus 6% with supportive care alone, though it did not prevent GFR loss in all patients and was associated with substantial adverse events in some studies 5, 4.