What is the initial management for Immunoglobulin A (IgA) Nephropathy (IgAN)?

Management of IgA Nephropathy (IgAN)

The initial management of IgA Nephropathy should focus on optimized supportive care with RAS blockade using ACEi or ARB as the cornerstone therapy, particularly for patients with proteinuria >0.5 g/day, regardless of blood pressure status. 1, 2

Risk Assessment and Initial Evaluation

• Assess risk of progression using:

  • Proteinuria level (key prognostic factor)
  • Blood pressure
  • eGFR at diagnosis
  • Pathological features (Oxford MEST-C score) 1, 2

• Identify variant forms requiring specific immediate treatment:

  • IgAN with minimal change disease
  • IgAN with acute kidney injury
  • IgAN with rapidly progressive glomerulonephritis (>50% crescents) 1

Supportive Care Algorithm

Step 1: RAS Blockade

• For proteinuria >0.5 g/day: Start ACEi or ARB (Grade 1B) 1, 2
• For proteinuria >1 g/day: RAS blockade is mandatory (Grade 1B) 2
• Titrate dose upward to achieve proteinuria <1 g/day 1, 2
• Do not delay RAS blockade even in normotensive patients 2

Step 2: Blood Pressure Control

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

Step 3: Lifestyle Modifications

• Dietary sodium restriction (<2 g/day)
• Smoking cessation
• Weight control (if overweight/obese)
• Regular exercise 2

Step 4: Consider SGLT2 Inhibitors

• May be beneficial in reducing CKD progression even in non-diabetic patients 1, 2
• Supported by recent evidence from DAPA-CKD and EMPA-KIDNEY trials 1

Management of Persistent Proteinuria

If proteinuria remains >1 g/day despite 3-6 months of optimized supportive care:

For Patients with eGFR >50 ml/min/1.73 m²:

• Consider a 6-month course of corticosteroid therapy (Grade 2C) 1, 2
• Corticosteroid regimens:
  • IV methylprednisolone 1g for 3 days, OR
  • Oral prednisone 0.8-1 mg/kg/day for 2 months with tapering over 6 months 1

For Patients with Persistent Proteinuria >1 g/day:

• Consider fish oil supplementation (Grade 2D) 1, 2

Management of Variant Forms

Crescentic IgAN (>50% crescents with rapidly progressive deterioration):

• Treat with corticosteroids and cyclophosphamide similar to ANCA vasculitis 1, 2

IgAN with Minimal Change Disease:

• Treat according to minimal change disease guidelines 1, 2

IgAN with Acute Kidney Injury from Severe Hematuria:

• Focus on supportive care for AKI
• Consider repeat biopsy if no improvement within 2 weeks 2

Treatments to Avoid

• Dual RAS blockade (ACEi + ARB) due to increased risk of hyperkalemia without proven additional benefit 1
• MMF in general IgAN (Grade 2C) 1, 2
• Antiplatelet agents (Grade 2C) 2
• Tonsillectomy (Grade 2C) 2
• Corticosteroids in patients with:
  • eGFR <30 ml/min/1.73 m²
  • Diabetes
  • Obesity (BMI >30 kg/m²)
  • Latent infections
  • Active peptic ulcer
  • Uncontrolled psychiatric disease
  • Severe osteoporosis 2

Monitoring

• Regular assessment of proteinuria, eGFR, and blood pressure
• Target reduction of proteinuria to <1 g/day as a surrogate marker of improved renal outcome 2, 3
• Patients who fail to achieve remission typically have lower baseline eGFR, lower serum albumin, hyperuricemia, and higher proteinuria 3

Emerging Therapies

New targeted therapies are being evaluated, including:

• Sparsentan (dual endothelin-1 and angiotensin II receptor blocker)
• Nefecon (targeted release formulation of budesonide)
• Iptacopan (complement factor B inhibitor) 4

Meticulous supportive therapy with optimal use of ACEi/ARB can achieve remission in approximately half of IgAN patients, with improved rates when treatment is extended to 6 months 3. Time-averaged low BP values are independently associated with decreased risk of renal progression, with no evidence of harm even at SBP levels below 125 mmHg 5.

Human studies have demonstrated that aggressive blood pressure control and RAS blockade remain the cornerstone of IgAN management, with immunosuppressive therapy reserved for specific high-risk cases 6, 7.