What is the initial treatment for immunoglobulin A (IgA) nephropathy (iGAN)?

Initial Treatment for IgA Nephropathy (IgAN)

The initial treatment for IgA nephropathy should focus on optimized supportive care with ACE inhibitors or ARBs for patients with proteinuria ≥0.5 g/day, with appropriate blood pressure targets based on proteinuria level. 1, 2

Risk Assessment

• Assess risk of progression through evaluation of proteinuria, blood pressure, and eGFR at diagnosis and during follow-up 1
• Consider pathological features using Oxford MEST score (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, and tubular atrophy/interstitial fibrosis) to help assess prognosis 1
• Monitor for reduction in proteinuria to <1 g/day, which is associated with favorable outcomes regardless of treatment approach 1

First-Line Treatment: Supportive Care

Blood Pressure and Proteinuria Management

• For patients with proteinuria ≥0.5 g/day, initiate ACE inhibitor or ARB treatment (1B evidence for proteinuria ≥1 g/day; 2D evidence for proteinuria between 0.5-1 g/day) 1
• Titrate ACE inhibitor or ARB upward as tolerated to achieve proteinuria <1 g/day 1
• Set blood pressure targets at <130/80 mmHg for patients with proteinuria <1 g/day and <125/75 mmHg for patients with proteinuria ≥1 g/day 1
• Registry data suggest that achieving proteinuria <1 g/day, either at diagnosis or after therapy, leads to better prognosis in IgAN 1
• Consider adding SGLT2 inhibitors to ACE inhibitor or ARB therapy, as recent trials like DAPA-CKD and EMPA-KIDNEY have shown kidney benefits in non-diabetic kidney disease including IgAN 1

Lifestyle Modifications

• Provide lifestyle advice including dietary sodium restriction, smoking cessation, weight control, and exercise 1
• Other than sodium restriction, no specific dietary intervention has been proven to alter outcomes in IgAN 1

Second-Line Treatment: Immunosuppression

Corticosteroid Therapy

• For patients with persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care and GFR >50 ml/min/1.73m², consider a 6-month course of corticosteroid therapy 1
• An Italian trial demonstrated long-term benefit with a 6-month course of IV and oral steroids versus no immunosuppression, with 10-year renal survival of 97% versus 53% 1
• Effective corticosteroid regimens include IV bolus injections of 1g methylprednisolone for 3 days at months 1,3, and 5, plus oral prednisone 0.5-1 mg/kg/day for 2 months followed by tapering over 4 months 1

Other Immunosuppressive Agents

• Do not use corticosteroids combined with cyclophosphamide or azathioprine in IgAN patients unless there is crescentic IgAN with rapidly deteriorating kidney function 1
• Do not use immunosuppressive therapy in patients with GFR <30 ml/min/1.73m² unless there is crescentic IgAN with rapidly deteriorating kidney function 1
• Do not use mycophenolate mofetil (MMF) in IgAN 1

Additional Therapies

Fish Oil

• Consider fish oil for patients with persistent proteinuria >1 g/day despite 3-6 months of optimized supportive care 1
• Evidence for fish oil is limited but may provide additional benefit in some patients 3

Special Situations

Minimal Change Disease with IgA Deposits

• Treat as for minimal change disease in nephrotic patients showing pathological findings of minimal change disease with mesangial IgA deposits on kidney biopsy 1

Crescentic IgA Nephropathy

• Define crescentic IgAN as IgAN with crescents in more than 50% of glomeruli with rapidly progressive renal deterioration 1
• Treat with steroids and cyclophosphamide, analogous to the treatment of ANCA vasculitis 1

Common Pitfalls and Caveats

• Do not delay initiation of ACE inhibitor/ARB therapy in patients with proteinuria ≥0.5 g/day 1, 2
• For patients with minimal proteinuria (<0.5 g/day), normal blood pressure, and normal renal function, treatment with ACE inhibitors may not offer significant benefit 4
• Avoid using tonsillectomy for treatment of IgAN as evidence does not support this approach 2
• Do not use antiplatelet agents specifically to treat IgAN 2, 5
• Be aware that many older clinical trials had suboptimal blood pressure goals (140/90 mmHg), which are now considered inadequate for optimal renoprotection 1
• The treatment landscape for IgAN is evolving rapidly, with newer agents targeting disease pathophysiology in development 6, 7