Management of IgA Nephropathy
The primary focus of IgA nephropathy management should be multifaceted, optimized supportive care, including RAS blockade as much as tolerated, blood pressure control, cardiovascular risk minimization, and lifestyle modifications. 1
Initial Assessment and Risk Stratification
- Following biopsy-confirmed diagnosis, assess disease prognosis using the MEST-C scoring system (mesangial and endocapillary hypercellularity, segmental glomerulosclerosis, interstitial fibrosis/tubular atrophy, and crescents) 1
- The International IgAN Prediction Tool (available at Calculate by QxMD) can help assess prognosis, though it cannot determine the likely impact of specific treatments 1
- Patients with proteinuria >0.75-1 g/day despite optimized supportive care have a high risk of progressive kidney function loss 1
First-Line Management: Optimized Supportive Care
- Initiate RAS blockade (ACE inhibitors or ARBs) for all patients with proteinuria >0.5 g/day, regardless of hypertension status (Grade 1B) 1, 2
- Implement strict blood pressure control targeting 125/75 mmHg 3
- Provide comprehensive lifestyle modifications:
- Maintain high fluid intake and avoid nephrotoxins 2
- Correct hyperlipidemia 2
- Administer pneumococcal and influenza vaccines 1
Management of High-Risk Patients
For patients with persistent proteinuria >0.75-1 g/day despite at least 90 days of optimized supportive care:
- Consider a 6-month course of glucocorticoid therapy (Grade 2B) or enrollment in a clinical trial 1
- Proteinuria reduction to under 1 g/day is a surrogate marker of improved kidney outcome and a reasonable treatment target 1, 4
Glucocorticoid Therapy Considerations
Glucocorticoids should be used with extreme caution or avoided in patients with:
- eGFR <30 ml/min/1.73 m² 1
- Diabetes 1
- Obesity (BMI >30 kg/m²) 1
- Latent infections (viral hepatitis, tuberculosis) 1
- Secondary disease (liver cirrhosis) 1
- Active peptic ulceration 1
- Uncontrolled psychiatric disease 1
- Severe osteoporosis 1
Special Populations and Considerations
- For Chinese patients, mycophenolate mofetil may be used as a glucocorticoid-sparing agent (not recommended in non-Chinese patients) 1
- For Japanese patients, consider tonsillectomy (not recommended in non-Japanese patients) 1
- For patients with rapidly progressive IgAN with extensive crescent formation (>50% of glomeruli), offer cyclophosphamide and glucocorticoids following protocols for ANCA-associated vasculitis 1
- For patients with IgAN and minimal change disease features, treat according to minimal change disease protocols 1
- For patients with acute kidney injury from severe visible hematuria, focus on supportive care and consider repeat biopsy if no improvement within 2 weeks 1
Therapies Not Recommended
The following immunosuppressive therapies are not recommended for standard IgAN treatment:
- Azathioprine 1
- Cyclophosphamide (except in rapidly progressive IgAN) 1
- Calcineurin inhibitors 1
- Rituximab 1
Emerging Therapies
Several promising therapies are currently being evaluated:
- SGLT2 inhibitors 1, 5
- Sparsentan and atrasentan (endothelin receptor antagonists) 1, 5
- Hydroxychloroquine 1
- Enteric-coated budesonide targeting intestinal mucosal immune system 4, 5
- Complement inhibitors 4, 5
- B-cell targeted therapies 4, 5
Monitoring and Follow-up
- Assess proteinuria reduction as a surrogate marker of treatment response 1, 4
- Monitor for a reduction in the slope of GFR decline as a favorable outcome 1
- A 40% or greater decline in eGFR from baseline over 2-3 years suggests a poor outcome 1
- Offer participation in disease registries and clinical trials when available 1