IgA Nephropathy Treatment Guideline
All patients with IgA nephropathy should begin with optimized supportive care consisting of blood pressure control and ACE inhibitor or ARB therapy if proteinuria exceeds 0.5 g/day, with immunosuppression reserved only for high-risk patients with persistent proteinuria >0.75-1 g/day after at least 90 days of maximal supportive therapy. 1
Initial Treatment Approach: Optimized Supportive Care
Foundation for All Patients
The cornerstone of IgA nephropathy management is optimized supportive care, which must be implemented before considering any immunosuppressive therapy 1. This approach includes:
- Blood pressure management targeting <130/80 mmHg for proteinuria <1 g/day, and <125/75 mmHg when proteinuria exceeds 1 g/day 1
- ACE inhibitor or ARB therapy initiated when proteinuria exceeds 0.5 g/day, regardless of blood pressure status, with up-titration to maximally tolerated doses 1
- Lifestyle modifications including dietary sodium restriction, smoking cessation, weight control, and regular exercise 1
- Cardiovascular risk assessment with appropriate interventions 1
Important caveat: Dual ACE inhibitor and ARB therapy provides no additional benefit and increases hyperkalemia risk, so should be avoided 1
Emerging Supportive Therapies
SGLT2 inhibitors should be strongly considered as add-on therapy to ACE inhibitors/ARBs, based on compelling evidence from trials like DAPA-CKD showing a 36% reduction (hazard ratio 0.64) in the composite outcome of 50% eGFR reduction or kidney failure in patients with glomerulonephritis 1. While not yet specifically studied in IgAN-only populations, the EMPA-KIDNEY trial included over 800 IgAN patients with eGFR as low as 20 mL/min 1.
Treatment Target
Proteinuria reduction to <1 g/day is the reasonable treatment target, as this serves as a surrogate marker for improved kidney outcomes 1. This target should guide the intensity of supportive care interventions.
High-Risk Patients: When to Consider Immunosuppression
Risk Stratification
High-risk patients are defined as those with proteinuria >0.75-1 g/day despite at least 90 days (3 months) of optimized supportive care 1. The KDIGO 2021 guidelines emphasize that patients in clinical trials showing benefit from immunosuppression had average proteinuria of 2.4 g/day 1.
Glucocorticoid Therapy
For high-risk patients with eGFR ≥30 mL/min/1.73 m², a 6-month course of glucocorticoid therapy may be considered, but only after individualized risk-benefit discussion 1. The evidence shows early efficacy but comes with significant treatment-associated morbidity and mortality from the TESTING trial 1.
Glucocorticoids should be avoided or used with extreme caution in patients with: 1
- eGFR <30 mL/min/1.73 m²
- Diabetes mellitus
- Obesity (BMI >30 kg/m²)
- Latent infections (tuberculosis, hepatitis B/C, HIV)
- Advanced age
- Metabolic syndrome
- Active peptic ulceration
- Uncontrolled psychiatric disease
- Severe osteoporosis
Other Immunosuppressive Agents
Most immunosuppressive therapies are NOT recommended including azathioprine, calcineurin inhibitors, and rituximab 1.
Population-specific exceptions: 1
- Chinese patients: Mycophenolate mofetil may be used as a glucocorticoid-sparing agent
- Japanese patients: Tonsillectomy may be considered in select cases
Critical point: Adverse treatment effects increase substantially when eGFR falls below 50 mL/min/1.73 m² 1
Special Clinical Situations
Rapidly Progressive IgA Nephropathy
Patients with crescentic IgAN (>50% crescents) and rapidly declining GFR should receive cyclophosphamide plus glucocorticoids, following protocols similar to ANCA-associated vasculitis 1. This is the only scenario where cyclophosphamide is recommended 1.
IgAN with Minimal Change Disease Features
Treat according to minimal change disease protocols when kidney biopsy shows mesangial IgA deposition with histologic features otherwise consistent with MCD 1
Acute Kidney Injury with Macroscopic Hematuria
Provide supportive care for AKI, and consider repeat kidney biopsy if no improvement occurs within 2 weeks after hematuria cessation 1. This distinguishes tubular obstruction from erythrocyte casts versus true crescentic disease 1.
Clinical Trial Enrollment
All high-risk patients should be offered enrollment in clinical trials given the current uncertainty about safety and efficacy of existing immunosuppressive options 1. Emerging therapies under investigation include enteric-coated budesonide, complement inhibitors, sparsentan, atrasentan, and B-cell targeted therapies 1.
Common Pitfalls to Avoid
- Do not use fish oil, antiplatelet agents, or routine tonsillectomy (except in Japanese populations) as these lack sufficient evidence 1
- Do not base treatment decisions solely on Oxford MEST-C score or crescent count without considering the clinical context 1
- Do not use the International IgAN Prediction Tool to determine treatment response or guide immunosuppression decisions 1
- Do not initiate immunosuppression without first completing at least 90 days of optimized supportive care 1