Initial Treatment Recommendations for IgA Nephropathy
The initial treatment for IgA nephropathy should focus on long-term ACE inhibitor or ARB therapy for patients with proteinuria ≥1 g/day, with up-titration based on blood pressure control, followed by corticosteroid therapy for persistent proteinuria despite optimized supportive care. 1
Risk Assessment and Monitoring
- Assess risk of progression through evaluation of proteinuria, blood pressure, and eGFR at diagnosis and during follow-up 1
- Consider pathological features (such as Oxford MEST score) 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 proteinuria ≥1 g/day: Recommend long-term ACE inhibitor or ARB treatment (1B evidence) 1
- For proteinuria between 0.5-1 g/day: Suggest ACE inhibitor or ARB treatment (2D evidence) 1
- Titrate ACE inhibitor or ARB upward as tolerated to achieve proteinuria <1 g/day 1
- Blood pressure targets:
- Consider dual blockade of renin-angiotensin system with both ACE inhibitor and ARB for patients at high risk of progression 2, 3
Second-Line Treatment: Immunosuppression
Corticosteroid Therapy
- For patients with persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care (ACE inhibitor/ARB and blood pressure control) and GFR >50 ml/min/1.73m², suggest a 6-month course of corticosteroid therapy 1
- Corticosteroid regimens that have shown efficacy include:
- 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
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
- Fish oil has a rationale for treating renal inflammation and preventing cardiovascular morbidity, though evidence for benefit is mixed 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
Prognostic Factors and Treatment Response
- Lower proteinuria and lower blood pressure are associated with slower eGFR decline and lower risk of end-stage kidney disease 4
- Baseline eGFR, proteinuria at 6 months, and systolic BP control at 6 months are independently associated with kidney failure events 4
- Reduction of proteinuria to <1 g/day is associated with favorable outcomes, regardless of how this is achieved 1, 4
Common Pitfalls and Caveats
- Do not delay initiation of ACE inhibitor/ARB therapy in patients with proteinuria ≥0.5 g/day 1, 5
- Avoid using tonsillectomy for treatment of IgAN as evidence does not support this approach 1
- Do not use antiplatelet agents specifically to treat IgAN 1
- Recognize that even patients with "favorable" clinical features at onset (normal renal function, proteinuria <1 g/24h, absence of hypertension) may still develop end-stage renal disease and require treatment 6
- Be aware that many clinical trials had suboptimal blood pressure goals (140/90 mmHg), which are now considered inadequate for optimal renoprotection 1