What is the current management approach for a patient with IgA (Immunoglobulin A) Nephropathy?

Recent Management of IgA Nephropathy

The cornerstone of IgA nephropathy management is optimized supportive care with RAS blockade, blood pressure control, and lifestyle modifications for at least 3 months before considering any immunosuppressive therapy. 1

Initial Management: Optimized Supportive Care (All Patients)

RAS Blockade

• Initiate ACE inhibitors or ARBs for all patients with proteinuria >0.5 g/day, regardless of whether hypertension is present (Grade 1B recommendation). 1, 2
• Titrate to maximally tolerated doses before considering any additional therapy. 1

Blood Pressure Targets

• Target <130/80 mmHg for patients with proteinuria <1 g/day. 2
• Target <125/75 mmHg for patients with proteinuria >1 g/day. 2, 3

Lifestyle and Dietary Modifications

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day). 1
• Normalize body mass index and limit central obesity through regular physical activity. 1
• Consider dietary protein restriction based on degree of proteinuria and kidney function level. 1
• Smoking cessation is essential. 1

Treatment Target

• Aim to reduce proteinuria to <1 g/day, which serves as a surrogate marker for improved kidney outcomes. 1, 3

High-Risk Patients: When to Consider Immunosuppression

Definition of High-Risk

Patients with persistent proteinuria >0.75-1 g/day despite at least 90 days (3 months) of optimized supportive care are considered high-risk for progression. 1, 3

Glucocorticoid Therapy Algorithm

For patients meeting high-risk criteria:

1. If eGFR ≥30 mL/min/1.73 m²: Consider a 6-month course of glucocorticoids (Grade 2B). 1, 3

2. Absolute contraindications to glucocorticoids (avoid entirely or use extreme caution): 1

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

3. Important caveat: The TESTING study demonstrated efficacy in reducing proteinuria but at the expense of significant treatment-associated morbidity and mortality, particularly infectious complications. 1 This underscores why glucocorticoids should be used cautiously and only after thorough risk-benefit discussion with the patient. 1

Preferred Alternative: Clinical Trial Enrollment

Enrollment in a clinical trial should be strongly considered as the preferred option over glucocorticoids for high-risk patients. 1

Immunosuppressive Agents NOT Recommended

The following agents are not recommended for routine use in IgA nephropathy: 1, 3

• Azathioprine (except after cyclophosphamide in crescentic disease)
• Cyclophosphamide (except in rapidly progressive IgAN with extensive crescents)
• Calcineurin inhibitors (CNIs)
• Rituximab
• Mycophenolate mofetil (MMF) in non-Chinese patients

Population-Specific Exceptions

• Chinese patients: MMF may be used as a glucocorticoid-sparing agent. 1
• Japanese patients: Tonsillectomy may be considered. 1

Special Clinical Situations

Rapidly Progressive IgAN (RPGN)

• Defined by extensive crescent formation (usually >50% of glomeruli) with declining GFR. 1, 3
• Treatment: Cyclophosphamide plus glucocorticoids is appropriate in this specific scenario. 1, 3

IgAN with Minimal Change Disease Features

• Treat according to minimal change disease guidelines, not standard IgAN protocols. 1

IgAN with Acute Kidney Injury from Gross Hematuria

• Focus on supportive care for AKI. 1
• Consider repeat kidney biopsy if no improvement within 2 weeks after hematuria cessation. 1

Emerging Therapies

Several new therapies are currently being evaluated and some have received regulatory approval: 1

Recently Approved

• Enteric-coated budesonide (Nefecon): FDA accelerated approval for primary IgAN with UPCR >1.5 g/g. 3
• SGLT2 inhibitors: Now being incorporated into treatment algorithms. 1
• Sparsentan: Dual endothelin-1 and angiotensin II receptor blocker. 1

Under Investigation

• Atrasentan (endothelin receptor antagonist) 1
• Complement inhibitors (iptacopan and others) 1
• Therapies targeting B-cell development 1
• Hydroxychloroquine 1

Critical Pitfalls to Avoid

• Never initiate immunosuppression without first optimizing supportive care for at least 3 months. 1, 2
• Do not use glucocorticoids in patients with eGFR <30 mL/min/1.73 m² unless dealing with rapidly progressive disease. 1
• Avoid NSAIDs (including aceclofenac) as they worsen kidney function and interfere with ACE inhibitor/ARB efficacy. 2
• Recognize that adverse effects from immunosuppression increase significantly when eGFR <50 mL/min/1.73 m². 1
• Do not rely solely on histologic scoring (MEST-C) or crescent presence to determine treatment regimen, as these cannot predict treatment response. 1

Monitoring Strategy

• Monitor proteinuria, blood pressure, and eGFR regularly to assess treatment response. 3
• Use the International IgAN Prediction Tool (available at Calculate by QxMD) for prognosis assessment. 1, 3
• Proteinuria reduction serves as the primary surrogate marker for treatment success. 1, 2