What are the latest guidelines for managing IgA (Immunoglobulin A) nephropathy?

Latest Guidelines for Managing IgA Nephropathy

The cornerstone of IgA nephropathy management is optimized supportive care, including RAS blockade with ACE inhibitors or ARBs for all patients with proteinuria >0.5 g/day, with additional therapies based on risk stratification and response to initial treatment. 1, 2

Initial Assessment and Risk Stratification

• Evaluate proteinuria, blood pressure, eGFR, and pathological features (Oxford MEST-C score)
• Use the International IgAN Prediction Tool (available at Calculate by QxMD) for prognosis assessment
• Identify high-risk patients: those with hypertension, proteinuria >1 g/day, and reduced GFR at diagnosis

First-Line Management: Optimized Supportive Care

Blood Pressure Control

• Target BP <130/80 mmHg if proteinuria <1 g/day
• Target BP <125/75 mmHg if proteinuria ≥1 g/day
• Sodium restriction (<2.0 g/day) enhances antiproteinuric effects

RAS Blockade

• ACE inhibitors or ARBs for all patients with proteinuria >0.5 g/day (Grade 1B) 1
• Titrate to maximum tolerated dose
• Consider dual RAS blockade (ACE inhibitor + ARB) for enhanced proteinuria reduction

Lifestyle Modifications

• Dietary sodium restriction (<2.0 g/day)
• Weight normalization and regular physical activity
• Smoking cessation
• Consider dietary protein restriction based on proteinuria level and kidney function

Second-Line Therapy for High-Risk Patients

For patients with persistent proteinuria >1 g/day despite 3 months of optimized supportive care:

Glucocorticoid Therapy (Grade 2B)

• Consider a 6-month course of glucocorticoids if eGFR ≥30 ml/min/1.73 m² 1
• Recommended regimen: methylprednisolone 1g IV for 3 days at months 1,3, and 5, plus oral prednisone 0.8-1 mg/kg/day for 2 months, then tapered over 4 months 2

Contraindications/Cautions for Glucocorticoids

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

Special Populations and Situations

Population-Specific Recommendations

• Chinese patients: Consider mycophenolate mofetil as a glucocorticoid-sparing agent 1
• Japanese patients: Consider tonsillectomy 1

Variant Forms of IgAN

• IgA with minimal change disease: Treat according to MCD guidelines
• IgA with nephrotic syndrome and mesangioproliferative GN: Treat as high-risk IgAN
• IgA with AKI from severe hematuria: Focus on supportive care
• Rapidly progressive IgAN (>50% crescents): Consider cyclophosphamide and corticosteroids 1

Emerging Therapies

Several new therapies are being evaluated or have been recently approved 3:

• SGLT2 inhibitors
• Sparsentan (dual endothelin-1 and angiotensin II receptor blocker)
• Nefecon (targeted-release formulation of budesonide)
• Iptacopan (complement factor B inhibitor)
• Other complement inhibitors and B-cell targeting therapies

Monitoring and Follow-up

• Regular monitoring of proteinuria, renal function (serum creatinine, eGFR), blood pressure, and hematuria
• Target proteinuria reduction to <1 g/day as a surrogate marker of improved kidney outcome 1
• Consider repeat kidney biopsy if no improvement in kidney function within 2 weeks following cessation of hematuria

Treatments to Avoid

• Azathioprine (except in rapidly progressive IgAN)
• Cyclophosphamide (except in rapidly progressive IgAN)
• Calcineurin inhibitors
• Rituximab
• Mycophenolate mofetil in non-Chinese patients
• Tonsillectomy in non-Japanese patients

Pitfalls and Caveats

• Adverse treatment effects are more likely in patients with eGFR <50 ml/min/1.73 m²
• Nephrotic-range proteinuria without nephrotic syndrome may reflect secondary FSGS or extensive glomerulosclerosis
• Clinical benefit of glucocorticoids is not firmly established; carefully weigh risks and benefits
• Consider clinical trial enrollment for patients with persistent proteinuria despite optimized care