IgA Nephropathy Management
All patients with IgA nephropathy should begin with optimized supportive care as the cornerstone of management, including ACE inhibitor or ARB therapy for proteinuria >0.5 g/day, blood pressure control, and lifestyle modifications, before considering any immunosuppressive therapy. 1
Initial Assessment and Risk Stratification
After biopsy-confirmed diagnosis, score the kidney biopsy using the MEST-C system (mesangial and endocapillary hypercellularity, segmental glomerulosclerosis, interstitial fibrosis/tubular atrophy, and crescents) to assess prognosis. 1, 2
Use the International IgAN Prediction Tool (available at Calculate by QxMD) to quantify progression risk and inform shared decision-making, though recognize this tool cannot predict treatment response. 1
Exclude secondary causes including IgA vasculitis, HIV, hepatitis, inflammatory bowel disease, autoimmune disease, and liver cirrhosis before proceeding with treatment. 1
First-Line Management: Optimized Supportive Care (All Patients)
Blood Pressure and Proteinuria Control
Initiate ACE inhibitor or ARB therapy for all patients with proteinuria >0.5 g/day, regardless of blood pressure status (Grade 1B). 1 This represents a significant change from older guidelines that used a 1 g/day threshold. 1
Target blood pressure according to general glomerular disease guidelines (typically <120/80 mmHg for patients with proteinuria). 1
Do not use dual ACE inhibitor and ARB therapy—subgroup analyses from STOP-IgAN showed no additional benefit and increased hyperkalemia risk. 1
Consider adding SGLT2 inhibitors to ACE inhibitor/ARB therapy based on DAPA-CKD and EMPA-KIDNEY trial data showing significant kidney outcome benefits in glomerulonephritis patients. 1
Lifestyle and Dietary Modifications
Restrict dietary sodium to <2.0 g/day (<90 mmol/day) to reduce edema, control blood pressure, and reduce proteinuria. 1, 2
Restrict dietary protein to 0.8-1 g/kg/day for patients with nephrotic-range proteinuria or eGFR <60 mL/min/1.73 m², emphasizing plant-based protein sources. 1
Target caloric intake of 35 kcal/kg/day (or 30-35 kcal/kg/day if eGFR <60 mL/min/1.73 m²) to achieve normal body mass index. 1
Counsel on smoking cessation, weight control, and regular exercise. 1
Cardiovascular Risk Management
Assess cardiovascular risk at diagnosis and initiate appropriate interventions, as proteinuria >0.5 g/day warrants cardiovascular risk consideration. 1, 3
Restrict dietary fat to <30% of total calories with mono- or polyunsaturated fat comprising 7-10% of total calories for patients with elevated cholesterol. 1
Management After 90 Days of Optimized Supportive Care
Low-Risk Patients (Proteinuria <0.75-1 g/day)
Continue optimized supportive care with close monitoring of proteinuria, blood pressure, and eGFR. 1
Target proteinuria reduction to <1 g/day as a surrogate marker of improved kidney outcomes. 1, 2
High-Risk Patients (Proteinuria ≥0.75-1 g/day Despite Optimized Care)
For patients with persistent proteinuria ≥0.75-1 g/day after at least 90 days of optimized supportive care, consider enrollment in a clinical trial as the preferred option, or alternatively a 6-month course of glucocorticoid therapy (Grade 2B). 1, 2
Glucocorticoid Therapy Considerations
Exercise extreme caution or avoid glucocorticoids entirely in patients with: 1
- eGFR <30 mL/min/1.73 m²
- Diabetes mellitus
- Obesity (BMI >30 kg/m²)
- Latent infections (viral hepatitis, tuberculosis, HIV)
- Secondary disease (liver cirrhosis)
- Active peptic ulceration
- Uncontrolled psychiatric disease
- Severe osteoporosis
The clinical benefit of glucocorticoids in IgAN is not definitively established, and the TESTING study showed treatment-associated morbidity and mortality despite evidence of efficacy. 1, 4
Adverse events from glucocorticoids markedly increase as eGFR declines, particularly with eGFR <50 mL/min/1.73 m². 1, 4
Population-Specific Considerations
Chinese Patients
Mycophenolate mofetil may be used as a glucocorticoid-sparing agent in Chinese patients, though it is not recommended in non-Chinese patients. 1, 2
Japanese Patients
Consider tonsillectomy in Japanese patients with high-risk IgAN, though this is not recommended in non-Japanese patients due to lack of data. 1, 2
Variant Forms Requiring Specific Immediate Treatment
Rapidly Progressive IgAN with Crescents
For patients with rapidly progressive glomerulonephritis and extensive crescent formation (>50% of glomeruli), offer cyclophosphamide and glucocorticoids following protocols for ANCA-associated vasculitis. 1, 2
IgAN with Minimal Change Disease
This variant may require specific immediate treatment distinct from standard IgAN management. 1
IgAN with Acute Kidney Injury
This variant may require specific immediate treatment distinct from standard IgAN management. 1
Therapies NOT Recommended
Do not use the following immunosuppressive agents for standard IgAN treatment: 1, 2
- Azathioprine
- Cyclophosphamide (except in rapidly progressive IgAN)
- Calcineurin inhibitors
- Rituximab
Monitoring and Treatment Targets
Monitor proteinuria reduction as the primary surrogate marker of treatment response, with a target of <1 g/day. 1, 2
Monitor for reduction in the slope of eGFR decline as a favorable outcome. 2
A 40% or greater decline in eGFR from baseline over 2-3 years suggests poor outcome and may warrant treatment escalation. 2
Emerging Therapies
Several new therapies are currently being evaluated in clinical trials, including targeted-release budesonide (nefecon), complement inhibitors (iptacopan), dual endothelin-1 and angiotensin II receptor blockers (sparsentan), and therapies targeting B-cell development. 1, 5
Offer participation in disease registries and clinical trials whenever available, as this represents the preferred approach for high-risk patients. 1, 2
Common Pitfalls to Avoid
Do not initiate immunosuppressive therapy before completing at least 90 days of optimized supportive care, as many patients will respond to supportive measures alone. 1
Do not use the International IgAN Prediction Tool or MEST-C score to determine treatment response or guide specific therapy selection—these are prognostic tools only. 1
Do not overlook cardiovascular risk assessment, as sub-nephrotic proteinuria is an independent cardiovascular risk factor in IgAN. 3