What is the recommended treatment for a pediatric patient with IgA (Immunoglobulin A) nephropathy?

Treatment of IgA Nephropathy in Pediatric Patients

Start all pediatric IgA nephropathy patients with ACE inhibitor or ARB therapy when proteinuria is between 0.5-1 g/day per 1.73 m², and escalate to corticosteroids only if proteinuria persists >1 g/day per 1.73 m² after 3-6 months of optimized RAS blockade. 1

Initial Management: RAS Blockade

Indications for ACE-I/ARB Therapy

• Begin ACE-I or ARB when proteinuria is 0.5-1 g/day per 1.73 m² 1
• Mandatory treatment when proteinuria exceeds 1 g/day per 1.73 m² with up-titration based on blood pressure tolerance 1
• Target proteinuria reduction to <1 g/day per 1.73 m² rather than complete normalization, as attempting to reach <0.5 g/day increases side effects without proven benefit 2, 3

Blood Pressure Targets

• Maintain blood pressure below the 90th percentile for age and gender 1
• Use BP target of 130/80 mmHg when proteinuria is <1 g/day 1
• Use stricter BP target of 125/75 mmHg when proteinuria exceeds 1 g/day 1

Evidence for ACE-I/ARB in Children

The IgACE trial demonstrated that benazepril (0.2 mg/kg/day) significantly reduced the composite endpoint of >30% decrease in creatinine clearance or worsening proteinuria (3.1% vs 26.5% in placebo, p=0.035), with 40.6% achieving partial remission versus 8.8% with placebo 4. Lisinopril (0.4 mg/kg/day) achieved proteinuria remission in 80.9% of children with mild IgA nephropathy over 2 years 5. The most common side effect is dizziness (12.5% of patients), which may require dose reduction but rarely necessitates discontinuation 5.

Escalation to Corticosteroids

Indications

Add a 6-month course of corticosteroid therapy when: 1

• Proteinuria persists >1 g/day per 1.73 m² despite 3-6 months of optimized ACE-I/ARB therapy
• GFR remains >50 ml/min per 1.73 m²
• Patient has preserved renal function to justify growth-related risks 1

Corticosteroid Regimen

Use either of these evidence-based protocols: 1

• IV methylprednisolone: 1 gram daily for 3 consecutive days at months 1,3, and 5
• Oral prednisone/prednisolone: Start 0.8-1 mg/kg/day for 2 months, then taper by 0.2 mg/kg/day monthly for 4 months (total 6-month course)

The Italian trial demonstrated 10-year renal survival of 97% with corticosteroids versus 53% without immunosuppression 1.

Critical Pitfall to Avoid

Do NOT start corticosteroids early for mild proteinuria without an adequate 3-6 month trial of ACE-I/ARB therapy. Given corticosteroid side effects and the lack of objective evidence that decreasing proteinuria below 1 g/day per 1.73 m² improves outcomes, the potential risks of therapy must be weighed against goals set by expert opinion rather than data 1. Consider expected normal growth during treatment when deciding on corticosteroid therapy 1.

Special Clinical Scenarios

Crescentic IgA Nephropathy (Rapidly Progressive)

Define as: >50% of glomeruli with crescents on biopsy plus rapidly progressive renal deterioration 1

Treatment: Use high-dose IV methylprednisolone plus cyclophosphamide, following the same protocol as ANCA-associated vasculitis 1. This applies even when crescents approach 50% if there is rapid GFR decline, as sampling error may affect biopsy interpretation 1.

Minimal Change Disease with Mesangial IgA Deposits

Treat as minimal change disease when nephrotic patients show pathological findings of MCD with mesangial IgA deposits on kidney biopsy 1

Acute Kidney Injury with Macroscopic Hematuria

Provide general supportive care when biopsy shows only acute tubular necrosis and intratubular erythrocyte casts 1. Consider repeat biopsy only if no improvement after 5 days, though timing should be individualized based on prior episodes 1.

Therapies NOT Recommended

• Mycophenolate mofetil: No benefit demonstrated 1
• Corticosteroids combined with cyclophosphamide or azathioprine: Not recommended unless crescentic disease 1
• Fish oil, antiplatelet agents, tonsillectomy: Insufficient evidence 1
• Any immunosuppression when GFR <30 ml/min per 1.73 m²: Unless crescentic disease 1

Combination ACE-I/ARB Therapy

For children with heavy proteinuria who are partial responders or non-responders to ACE-I alone, adding low-dose ARB significantly augments antiproteinuric effect (p<0.01) without blood pressure changes, appearing both well-tolerated and safe 6. However, this approach requires careful monitoring and is not included in formal guideline recommendations.