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

Initial Management of IgA Nephropathy

Start all patients with optimized supportive care as the foundation of treatment: ACE inhibitor or ARB therapy for proteinuria >0.5 g/day regardless of blood pressure, strict BP control, lifestyle modifications, and cardiovascular risk reduction. 1, 2, 3

Step 1: Confirm Diagnosis and Assess Risk

• Obtain kidney biopsy with MEST-C histologic scoring (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents) to confirm diagnosis and guide prognosis 1, 2
• Use the International IgAN Prediction Tool (available at Calculate by QxMD) to assess risk of progression based on proteinuria, blood pressure, eGFR, and biopsy findings 1, 2
• Exclude secondary causes of IgA nephropathy during initial evaluation 1

Step 2: Initiate Optimized Supportive Care (All Patients)

Blood Pressure Management

• Target **<125/75 mmHg** when proteinuria is >1 g/day 1, 3
• Target <130/80 mmHg when proteinuria is <1 g/day 1, 3

RAS Blockade

• Start ACE inhibitor or ARB for all patients with proteinuria >0.5 g/day, even if normotensive (Grade 1B) 1, 3
• Uptitrate to maximally tolerated doses to achieve proteinuria <1 g/day 1, 3
• Do not use dual ACE inhibitor plus ARB therapy due to lack of additional benefit and hyperkalemia risk 1

Lifestyle Modifications

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) 1, 3
• Achieve smoking cessation 1, 3
• Normalize body weight and limit central obesity 1, 3
• Implement regular exercise program 3, 4
• Maintain high fluid intake to avoid dehydration 4

Cardiovascular Risk Reduction

• Assess and treat dyslipidemia 3, 4
• Consider SGLT2 inhibitor addition to ACE inhibitor/ARB based on emerging evidence from DAPA-CKD and EMPA-KIDNEY trials, though IgAN-specific data are limited 1

Step 3: Monitor Response for 90 Days

• Measure proteinuria, blood pressure, and eGFR regularly during the initial 90-day period of optimized supportive care 1, 2
• The goal is to reduce proteinuria to <1 g/day, which serves as a surrogate marker for improved kidney outcomes 1, 2

Step 4: Consider Immunosuppression for High-Risk Patients

Only consider glucocorticoids if proteinuria remains >0.75-1 g/day after at least 90 days of optimized supportive care (Grade 2B) 1, 2, 3

Glucocorticoid Eligibility Criteria

• eGFR must be ≥30 mL/min/1.73 m² 1, 2, 3
• Avoid or use extreme caution in patients with: 1, 2, 3
  • Diabetes mellitus
  • Obesity (BMI >30 kg/m²)
  • Latent infections (hepatitis, tuberculosis)
  • Active peptic ulceration
  • Uncontrolled psychiatric disease
  • Severe osteoporosis
  • Advanced age or metabolic syndrome

Glucocorticoid Regimen

• Administer for 6 months maximum if used 1, 2
• Preferably enroll patients in clinical trials rather than using glucocorticoids, given uncertain benefit-risk profile 1, 3

Special Clinical Scenarios Requiring Different Approaches

Rapidly Progressive IgAN (Crescentic)

• Defined as >50% crescents on biopsy with declining GFR 2, 3
• Treat with cyclophosphamide plus glucocorticoids using protocols similar to ANCA-associated vasculitis 2, 3

IgAN with Minimal Change Disease Features

• Treat according to minimal change disease protocols when biopsy shows mesangial IgA with otherwise MCD histology 3

Acute Kidney Injury in IgAN

• Distinguish acute tubular necrosis (supportive care only) from crescentic disease (requires immunosuppression) 5

Therapies NOT Recommended for Routine Use

Avoid the following unless in specific populations or clinical scenarios: 1, 2

• Azathioprine
• Cyclophosphamide (except rapidly progressive IgAN)
• Calcineurin inhibitors
• Rituximab
• Mycophenolate mofetil (exception: may consider in Chinese patients as glucocorticoid-sparing agent) 1, 2
• Tonsillectomy (exception: may consider in Japanese patients) 1, 2

Common Pitfalls to Avoid

• Do not rush to immunosuppression: Give optimized supportive care a full 90-day trial first, as many patients respond without needing steroids 1, 3
• Do not use glucocorticoids in patients with eGFR <30 mL/min/1.73 m²: Risk of adverse events markedly increases as kidney function declines 1, 6
• Do not assume biopsy findings alone determine treatment: Neither MEST-C score nor crescent number can currently predict response to specific therapies 1
• Do not overlook ACE inhibitor nephrotoxicity: Monitor creatinine closely, especially with bilateral renal artery stenosis or advanced kidney disease 1

Emerging Therapies

• Enteric-coated budesonide has received FDA accelerated approval for primary IgA nephropathy with urine protein-to-creatinine ratio >1.5 g/g 2
• Multiple clinical trials are ongoing for complement inhibitors, B-cell targeted therapies, and endothelin antagonists 6, 7