What is the primary treatment approach for a patient with IgA (Immunoglobulin A) nephritis?

IgA Nephropathy Treatment

The primary treatment for IgA nephropathy is optimized supportive care with RAS blockade (ACE inhibitors or ARBs), blood pressure control, and lifestyle modifications for at least 90 days before considering any immunosuppression. 1, 2

Initial Management: Optimized Supportive Care (All Patients)

RAS Blockade

• Initiate ACE inhibitor or ARB therapy immediately for any patient with proteinuria ≥0.5 g/day, regardless of blood pressure status (Grade 1B). 1, 2, 3
• Titrate upward as tolerated to achieve proteinuria <1 g/day. 2, 3
• This is the cornerstone of therapy and must be maximized before considering any immunosuppression. 1, 2

Blood Pressure Targets

• Target <130/80 mmHg if proteinuria <1 g/day. 2, 3, 4
• Target <125/75 mmHg if proteinuria ≥1 g/day. 2, 3, 4

Lifestyle and Dietary Modifications

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day). 1
• Dietary protein restriction to 0.8-1 g/kg/day if nephrotic-range proteinuria or eGFR <60 ml/min/1.73 m². 1
• Smoking cessation, weight control targeting normal BMI, and regular exercise. 1, 2
• Target caloric intake 30-35 kcal/kg/day if eGFR <60 ml/min/1.73 m². 1

Duration of Supportive Care Trial

• Continue optimized supportive care for at least 90 days (preferably 3-6 months) before considering immunosuppression. 1, 3, 4
• Monitor proteinuria every 3 months during this period. 3, 4

Immunosuppression: High-Risk Patients Only

Indications for Glucocorticoid Therapy

Consider a 6-month course of glucocorticoids (Grade 2B) only if ALL of the following criteria are met: 1, 2, 3

• Persistent proteinuria ≥0.75-1 g/day despite at least 90 days of optimized supportive care
• eGFR >50 ml/min/1.73 m² (some sources suggest >30 ml/min/1.73 m² as the absolute cutoff)
• No contraindications to glucocorticoid therapy

Glucocorticoid Regimen

• Pozzi Protocol (preferred): IV methylprednisolone 1g for 3 consecutive days at months 1,3, and 5, plus oral prednisone 0.5 mg/kg on alternate days for 6 months. 3, 4
• This regimen showed 10-year renal survival of 97% versus 53% without immunosuppression in Italian trials. 4

Absolute Contraindications to Glucocorticoids

Do not use glucocorticoids in patients with: 1, 3

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

Prophylaxis During Immunosuppression

• Trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis jirovecii in patients receiving high-dose prednisone or other immunosuppressive agents. 1

Immunosuppressive Agents to AVOID

The following agents are NOT recommended in IgAN (except in specific circumstances): 1, 2, 3

• Azathioprine (except after cyclophosphamide in crescentic disease) 2, 3
• Cyclophosphamide (except in rapidly progressive IgAN with >50% crescents) 1, 2, 3
• Calcineurin inhibitors 1, 2
• Rituximab 1, 2
• Mycophenolate mofetil (no benefit in non-Chinese patients; may be used as glucocorticoid-sparing agent in Chinese patients only) 1, 2, 3

Special Clinical Scenarios

Rapidly Progressive/Crescentic IgAN

• Definition: >50% crescents on biopsy with rapidly progressive renal deterioration. 3, 4
• Treatment: Steroids plus cyclophosphamide analogous to ANCA vasculitis, regardless of baseline eGFR. 3, 4

IgAN with Minimal Change Disease Pattern

• Treatment: High-dose corticosteroids as for primary minimal change disease in nephrotic patients showing minimal light microscopic changes with mesangial IgA deposits. 3, 4

Treatment Goals and Monitoring

Primary Treatment Target

• Proteinuria reduction to <1 g/day is the surrogate marker of improved kidney outcomes and the reasonable treatment target. 1, 2, 3

Monitoring Schedule

• Check proteinuria every 3 months during and after treatment. 3, 4
• Monitor eGFR every 3-6 months to assess disease trajectory. 3
• Screen for glucose intolerance, monitor blood pressure, assess infection risk, and monitor weight gain in patients on corticosteroids. 3

Critical Pitfalls to Avoid

• Never initiate immunosuppression without first maximizing RAS blockade and achieving optimal blood pressure control for at least 90 days. 2, 4
• Never use immunosuppression in patients with eGFR <30 ml/min/1.73 m² unless there is crescentic disease with rapidly deteriorating kidney function. 2, 3, 4
• Never use NSAIDs (like aceclofenac) in IgAN patients, as they worsen kidney function and interfere with ACE inhibitor/ARB therapy. 2
• Never combine corticosteroids with cyclophosphamide or azathioprine unless treating crescentic IgAN. 3, 4
• Never overlook the importance of proteinuria monitoring as the primary marker of treatment success. 2, 3

Risk Stratification Tools

• Use the International IgAN Prediction Tool (available at Calculate by QxMD) to quantify risk of progression and inform shared decision-making. 1, 4
• Score kidney biopsy using the MEST-C system (mesangial and endocapillary hypercellularity, segmental glomerulosclerosis, interstitial fibrosis/tubular atrophy, and crescents). 1
• Important caveat: Neither the prediction tool nor MEST-C score can determine the likely impact of any particular treatment regimen. 1

Emerging Therapies

• Clinical trials with enteric-coated budesonide, B-cell blockade, and complement inhibitors are ongoing and may provide more targeted therapy options in the future. 5
• Patients should be offered participation in disease registries and clinical trials whenever available. 1