What is the recommended treatment for IgA (Immunoglobulin A) Nephropathy?

Treatment of IgA Nephropathy

All patients with IgA nephropathy should begin with optimized supportive care consisting of maximally tolerated ACE inhibitor or ARB therapy with strict blood pressure control for at least 3-6 months before considering any immunosuppression. 1

Initial Risk Stratification

• Measure 24-hour urine protein or spot urine protein-to-creatinine ratio at diagnosis to quantify proteinuria, as this drives all subsequent treatment decisions 2
• Calculate eGFR from serum creatinine to determine eligibility for immunosuppressive therapy 2
• Request Oxford MEST scoring on the kidney biopsy, as this provides independent prognostic information beyond clinical parameters 1, 2
• Quantify the percentage of crescents on biopsy to identify rapidly progressive disease requiring immediate aggressive treatment 2

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

Renin-Angiotensin System Blockade

• Initiate ACE inhibitor or ARB immediately for any patient with proteinuria ≥0.5 g/day, regardless of blood pressure 2, 3
• Titrate upward to the maximally tolerated dose to achieve proteinuria <1 g/day 1, 2
• Continue this therapy for a minimum of 3-6 months before considering any immunosuppression 1, 3

Blood Pressure Targets

• Target blood pressure <130/80 mmHg if proteinuria is <1 g/day 1, 2, 3
• Target blood pressure <125/75 mmHg if proteinuria is ≥1 g/day 1, 2, 3

Monitoring During Supportive Care

• Reassess proteinuria every 3 months during the initial supportive care period 2
• The goal is proteinuria reduction to <1 g/day, which is a surrogate marker for improved kidney outcomes 1, 4

Second-Line Treatment: Immunosuppression (High-Risk Patients Only)

Patient Selection Criteria

Consider a 6-month course of corticosteroid therapy only if ALL of the following criteria are met: 1, 2, 3

• Persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care
• eGFR >50 ml/min/1.73 m² (some guidelines use >30 ml/min/1.73 m² as the cutoff, but the most recent 2021 KDIGO guideline emphasizes caution below 50) 1
• Absence of absolute contraindications (see below)

Absolute Contraindications to Corticosteroids

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

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

Corticosteroid Regimen

• Use the Pozzi Protocol: IV methylprednisolone 1 gram for 3 consecutive days at months 1,3, and 5, plus oral prednisone 0.5 mg/kg on alternate days for 6 months 2, 3
• The risk/benefit profile of glucocorticoids should be individually discussed with each patient, as the TESTING study showed efficacy at the expense of treatment-associated morbidity and mortality 1

Monitoring During Immunosuppression

• Check proteinuria every 3 months during treatment with a goal of reduction to <1 g/day 2
• Screen for glucose intolerance, monitor blood pressure, assess infection risk, and monitor for weight gain 2

Therapies to Avoid in Typical IgA Nephropathy

The following immunosuppressive agents are NOT recommended for standard IgA nephropathy: 1, 4

• Mycophenolate mofetil (MMF) - no benefit demonstrated in non-Chinese patients 1, 2
• Azathioprine (except after cyclophosphamide in crescentic disease) 1, 4
• Cyclophosphamide (except in rapidly progressive crescentic disease) 1, 4
• Calcineurin inhibitors 1, 4
• Rituximab 1, 4
• Antiplatelet agents (dipyridamole) - low-quality evidence and poor adherence 1, 2, 4
• Routine tonsillectomy - not recommended unless recurrent tonsillitis with macroscopic hematuria 1, 2, 3

Special Clinical Scenarios

Crescentic IgA Nephropathy (Rapidly Progressive Disease)

• Define crescentic IgAN as >50% crescents on biopsy with rapidly progressive renal deterioration 1, 2, 3
• Treat immediately with steroids plus cyclophosphamide analogous to ANCA vasculitis, regardless of baseline eGFR 1, 2, 3
• This is the only scenario where cyclophosphamide is indicated in IgA nephropathy 1

IgA Nephropathy with Minimal Change Disease Pattern

• Treat as minimal change disease in nephrotic patients showing minimal light microscopic changes with mesangial IgA deposits 1, 2, 3
• Use high-dose corticosteroids as for primary minimal change disease 2

Acute Kidney Injury with Macroscopic Hematuria

• Perform repeat kidney biopsy if no improvement occurs within 5 days from onset of kidney function worsening 1
• Provide general supportive care if biopsy shows only acute tubular necrosis and intratubular erythrocyte casts 1

Population-Specific Considerations

• In Chinese patients, mycophenolate mofetil may be used as a glucocorticoid-sparing agent 1
• In Japanese patients, tonsillectomy may be considered in the context of recurrent tonsillitis 1

Adjunctive Therapies

• Consider fish oil supplementation for patients with persistent proteinuria >1 g/day despite 3-6 months of optimized supportive care, though evidence is conflicting 1, 2, 3

Common Pitfalls to Avoid

• Do not initiate immunosuppression without first optimizing supportive care for 3-6 months - this is the most common error 1, 4
• Do not use corticosteroids in patients with eGFR <30 ml/min/1.73 m² unless crescentic disease is present 1, 2
• Do not delay ACE inhibitor/ARB therapy in patients with proteinuria ≥0.5 g/day 3
• Do not overlook blood pressure control as a critical component of supportive care 4
• Consider enrollment in a clinical trial before initiating glucocorticoids, as newer therapies (SGLT2 inhibitors, sparsentan, enteric-coated budesonide, complement inhibitors) are currently being evaluated 1