What is the management and treatment of IgA (Immunoglobulin A) nephropathy?

Management and Treatment of IgA Nephropathy

All patients with IgA nephropathy should begin with optimized supportive care including maximally tolerated RAS blockade, blood pressure control to 125/75 mmHg, and lifestyle modifications; glucocorticoids should only be considered for high-risk patients with persistent proteinuria >1 g/day after at least 3 months of maximal supportive therapy, with careful attention to contraindications and toxicity risks. 1, 2

Risk Stratification After Diagnosis

Following biopsy confirmation, immediately assess disease prognosis using:

• MEST-C scoring system evaluating mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, interstitial fibrosis/tubular atrophy, and crescents 2
• Proteinuria level as the single most important clinical predictor—patients with proteinuria >0.75-1 g/day despite optimized care have high risk for progressive kidney function loss 2, 3
• International IgAN Prediction Tool to help assess prognosis, though it cannot determine treatment impact 2

First-Line Treatment: Optimized Supportive Care (All Patients)

This is the cornerstone and must be maximized before considering any immunosuppression:

RAS Blockade

• Initiate ACE inhibitors or ARBs for all patients with proteinuria >0.5 g/day, regardless of whether hypertension is present 2
• Titrate to maximally tolerated doses 1, 2

Blood Pressure Control

• Target blood pressure of 125/75 mmHg using RAS blockade as first-line 4
• This aggressive target applies even to normotensive patients with significant proteinuria 4

Lifestyle Modifications

• Dietary sodium restriction to <2.0 g/day (<90 mmol/day) 2
• Maintain desirable body weight 5
• Cessation of smoking 5
• Active exercise program 5
• High fluid intake 5

Additional Supportive Measures

• Administer pneumococcal and influenza vaccines 2
• Cardiovascular risk management with statins for any proteinuria >0.5 g/day 3
• Low protein/low phosphate diet with phosphate binders if renal impairment develops 5

Treatment Target

• Proteinuria reduction to <1 g/day is the surrogate marker of improved kidney outcome and reasonable treatment goal 1, 2

Management of High-Risk Patients (Persistent Proteinuria After Supportive Care)

For patients with proteinuria >0.75-1 g/day despite at least 90 days (3 months) of optimized supportive care and eGFR ≥30 mL/min/1.73 m²: 1, 2

Before Considering Glucocorticoids: Screen for Contraindications

Absolute contraindications to glucocorticoid therapy: 1

• Active infection (including latent tuberculosis)
• Secondary disease (e.g., liver cirrhosis)
• Active peptic ulceration
• Uncontrolled psychiatric disease
• Severe osteoporosis

Toxicity risk factors requiring individualized discussion: 1

• Advanced age
• Metabolic syndrome
• Obesity
• Latent infections (TB, HIV, HBV, HCV)
• eGFR <50 mL/min/1.73 m² (adverse effects more likely)

Glucocorticoid Therapy Decision

If no contraindications present:

• Consider a 6-month course of glucocorticoid therapy after detailed risk-benefit discussion with the patient 1, 2
• The TESTING trial showed efficacy in patients with marked proteinuria (average 2.4 g/day) but at the expense of treatment-associated morbidity and mortality 1
• Alternatively, prioritize enrollment in clinical trials evaluating newer therapies (SGLT2 inhibitors, sparsentan, atrasentan, enteric-coated budesonide, complement inhibitors) 1, 2

Population-Specific Considerations

Chinese Patients

• Mycophenolate mofetil may be used as a glucocorticoid-sparing agent 1, 2
• This is NOT recommended in non-Chinese patients 1, 2

Japanese Patients

• Consider tonsillectomy 1, 2
• This is NOT recommended in non-Japanese patients 1, 2

Therapies NOT Recommended for Standard IgAN

Do not use the following agents (except in specific variant presentations): 1, 2

• Azathioprine
• Cyclophosphamide (exception: rapidly progressive IgAN with crescents)
• Calcineurin inhibitors
• Rituximab
• Mycophenolate mofetil in non-Chinese patients

Special Clinical Situations Requiring Different Management

IgAN with Minimal Change Disease Features

• Treat according to minimal change disease guidelines, not standard IgAN protocols 1

Rapidly Progressive IgAN (RPGN with >50% Crescents)

• Offer cyclophosphamide and glucocorticoids following protocols for ANCA-associated vasculitis 1, 2
• This is the only indication for cyclophosphamide in IgAN 1

IgAN with Acute Kidney Injury from Severe Hematuria

• Focus on supportive care for AKI 1
• Consider repeat kidney biopsy if no improvement in kidney function within 2 weeks after hematuria cessation 1

Nephrotic Syndrome with Mesangioproliferative Features

• Manage as high-risk IgAN patients 1

Monitoring Treatment Response

Track the following parameters:

• Proteinuria reduction as surrogate marker of treatment response—goal <1 g/day 1, 2
• Reduction in slope of GFR decline as favorable outcome 2
• 40% or greater decline in eGFR from baseline over 2-3 years suggests poor outcome requiring treatment intensification 2

Critical Pitfalls to Avoid

The most common error is premature use of immunosuppression: The STOP-IgAN trial demonstrated that strict supportive care alone (including lifestyle changes, protein and salt restriction) provides substantial benefit, and many patients labeled as "high-risk" will respond to optimized supportive measures without needing glucocorticoids. 6 Always ensure a full 3-month trial of maximal supportive care before considering immunosuppression. 1, 2

Second major pitfall is using glucocorticoids in patients with eGFR <50 mL/min/1.73 m² without careful consideration, as adverse events increase markedly as GFR declines. 1, 7 In these patients, the risk-benefit ratio often favors continued supportive care or clinical trial enrollment over standard glucocorticoid therapy.