What is the management approach for IgA (Immunoglobulin A) nephropathy?

Management of IgA Nephropathy

All patients with IgA nephropathy should receive optimized supportive care as the primary treatment, including RAS blockade with ACE inhibitors or ARBs for proteinuria >0.5 g/day, blood pressure control targeting <125/75 mmHg when proteinuria exceeds 1 g/day, and cardiovascular risk reduction measures. 1, 2

Initial Assessment and Risk Stratification

• Confirm diagnosis via kidney biopsy showing mesangial dominant IgA deposits and score using the MEST-C histologic classification system 1, 3
• Exclude secondary causes including IgA vasculitis, HIV, hepatitis, inflammatory bowel disease, autoimmune disease, and liver cirrhosis 1, 3
• Use the International IgAN Prediction Tool to quantify progression risk based on clinical and histologic data at biopsy 1
• Assess baseline proteinuria, blood pressure, and eGFR as key prognostic markers 1

Optimized Supportive Care (First-Line for All Patients)

RAS Blockade

• Initiate ACE inhibitor or ARB for all patients with proteinuria >0.5 g/day, regardless of hypertension status 1, 2, 4
• Maximize tolerated dose before considering any immunosuppressive therapy 1, 4

Blood Pressure Management

• Target <130/80 mmHg for proteinuria <1 g/day 1, 4
• Target <125/75 mmHg for proteinuria >1 g/day 1, 4

Lifestyle and Dietary Modifications

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) 1
• Limit protein intake to 0.8-1 g/kg/day in nephrotic-range proteinuria, emphasizing plant-based sources 1
• Achieve normal body mass index through caloric restriction (35 kcal/kg/day, or 30-35 kcal/kg/day if eGFR <60) 1
• Implement smoking cessation, regular exercise, and avoid nephrotoxins including NSAIDs 4, 5

Cardiovascular Risk Reduction

• Manage hyperlipidemia with heart-healthy diet (dietary fat <30% of total calories) 1
• Address all modifiable cardiovascular risk factors 1, 2

Treatment Goal

• Aim to reduce proteinuria to <1 g/day as a surrogate marker of improved kidney outcomes 1, 2

Immunosuppressive Therapy (Second-Line for High-Risk Patients)

Indications for Glucocorticoids

Consider a 6-month course of glucocorticoids only if all of the following criteria are met: 1, 2

• Proteinuria remains >0.75-1 g/day despite at least 90 days (3 months) of optimized supportive care with maximally tolerated RAS blockade 1, 2
• eGFR ≥30 ml/min/1.73 m² (some guidelines suggest ≥50 ml/min/1.73 m²) 1, 2
• Absence of contraindications (see below)

Absolute Contraindications to Glucocorticoids

Glucocorticoids should be avoided entirely or given with extreme caution in patients with: 1

• eGFR <30 ml/min/1.73 m² 1
• Diabetes mellitus 1
• Obesity (BMI >30 kg/m²) 1
• Latent infections (viral hepatitis, tuberculosis, HIV) 1
• Secondary disease (liver cirrhosis) 1
• Active peptic ulceration 1
• Uncontrolled psychiatric disease 1
• Severe osteoporosis 1

Important Caveat on Glucocorticoid Use

The TESTING study demonstrated efficacy in reducing proteinuria but at the expense of significant treatment-associated morbidity and mortality, making the risk-benefit profile uncertain 1. A detailed discussion of risks and benefits must be undertaken with each patient before initiating glucocorticoid therapy. 1

Therapies NOT Recommended for Routine Use

The following immunosuppressive agents should NOT be used in typical IgAN: 1, 4

• Azathioprine (except after cyclophosphamide in crescentic disease) 1, 4
• Cyclophosphamide (except in rapidly progressive IgAN) 1, 4
• Calcineurin inhibitors 1, 4
• Rituximab 1, 4
• Mycophenolate mofetil in non-Chinese patients 1
• Fish oil (no longer recommended despite older guidelines) 1

Special Population Considerations

Chinese Patients

• May consider mycophenolate mofetil as a glucocorticoid-sparing agent 1, 2

Japanese Patients

• May consider tonsillectomy in high-risk patients 1, 2

Variant Forms Requiring Specific Management

IgAN with Minimal Change Disease Features

• Treat according to minimal change disease protocols with corticosteroids 1, 2

Rapidly Progressive (Crescentic) IgAN

Defined as: Crescents in >50% of glomeruli with rapidly declining kidney function 1

Treatment: Use cyclophosphamide plus glucocorticoids in a regimen analogous to ANCA vasculitis treatment 1, 2

IgAN with Acute Kidney Injury from Gross Hematuria

• Focus on supportive care with hydration 1
• Distinguish from acute tubular necrosis versus crescentic disease 6

Emerging Therapies

Several new therapies are currently approved or under investigation: 1, 2, 7

• Enteric-coated budesonide (nefecon) has received FDA accelerated approval for primary IgAN with UPCR >1.5 g/g 2
• SGLT2 inhibitors are being evaluated to augment supportive care 1, 7
• Sparsentan (dual endothelin-1 and angiotensin II receptor blocker) 1, 7
• Iptacopan (complement factor B inhibitor) 7
• Various complement inhibitors and B-cell targeted therapies are in clinical trials 1

Consider enrollment in clinical trials whenever available for high-risk patients. 1, 2

Monitoring Strategy

• Assess proteinuria, blood pressure, and eGFR regularly during follow-up 1
• Proteinuria reduction to <1 g/day indicates favorable response to therapy 1, 2, 4
• Adverse effects from immunosuppression increase markedly as eGFR declines, particularly below 50 ml/min/1.73 m² 1, 8

Critical Pitfalls to Avoid

• Never initiate immunosuppression without first optimizing supportive care for at least 3 months 1, 4
• Avoid NSAIDs entirely as they worsen kidney function, increase proteinuria, and interfere with ACE inhibitor/ARB efficacy 4
• Do not use glucocorticoids in patients with eGFR <30 ml/min/1.73 m² unless rapidly progressive disease 1, 4
• Recognize that most patients have a slowly progressive course and aggressive immunosuppression carries substantial risks that may outweigh benefits 8, 9