ACE Inhibitors and ARBs for Children with Henoch-Schönlein Purpura Nephritis
For children with Henoch-Schönlein purpura nephritis (HSPN) and persistent proteinuria, ACE inhibitors or ARBs should be used as first-line therapy, titrated to the maximum tolerated dose. 1
Initial Assessment and Treatment Algorithm
When to Start ACE Inhibitors or ARBs:
- Begin ACE inhibitors or ARBs when proteinuria persists at >0.5-1 g/day per 1.73 m² despite supportive care 1
- Start treatment after confirming persistent proteinuria (typically present for at least 4 weeks) 1
- Monitor baseline kidney function and electrolytes before initiating therapy
Medication Selection and Dosing:
- First choice: ACE inhibitor (such as enalapril, lisinopril)
- Starting dose: Weight-appropriate pediatric dosing
- Example: Enalapril 0.08 mg/kg/day initially, titrated up as needed
- Alternative: ARB (such as losartan) if ACE inhibitor not tolerated
- Use when ACE inhibitor causes cough or angioedema
- Starting dose: Weight-appropriate pediatric dosing
- Example: Losartan 0.7 mg/kg/day initially
Titration Strategy:
- Start at low dose
- Gradually increase to maximum tolerated dose over 2-4 weeks
- Target blood pressure: 50th percentile for age, sex, and height 1
- Monitor kidney function and electrolytes with each dose increase
Monitoring and Follow-up
Laboratory Monitoring:
- Check serum creatinine and potassium 1-2 weeks after initiation and with each dose increase
- Monitor urinary protein excretion every 1-2 months
- Assess complete blood count and urinalysis every 3 months
Target Goals:
- Reduce proteinuria to <1 g/day per 1.73 m² 1
- Maintain blood pressure at 50th percentile for age, sex, and height 1
- Preserve kidney function (stable eGFR)
Safety Considerations:
- Hold medication if serum creatinine increases >30% from baseline 1
- Discontinue if kidney function continues to worsen or refractory hyperkalemia develops 1
- Counsel patients/parents to temporarily stop medication during illness with risk of dehydration 1
Escalation of Therapy
When to Add Additional Therapy:
- If proteinuria persists >1 g/day per 1.73 m² after 3-6 months of optimized ACE inhibitor/ARB therapy 1
- If kidney function deteriorates despite ACE inhibitor/ARB therapy
- If nephrotic syndrome develops
Additional Treatment Options:
Add corticosteroids if GFR >50 ml/min per 1.73 m² and persistent proteinuria >1 g/day despite ACE inhibitor/ARB therapy 1
- 6-month course of corticosteroid therapy similar to IgA nephropathy protocol
Consider immunosuppressive agents for severe cases:
Special Considerations
Monitoring for Adverse Effects:
- Hyperkalemia (especially with reduced GFR)
- Acute kidney injury (particularly during intercurrent illness)
- Hypotension (more common in younger children)
- Angioedema (rare but potentially serious)
- Cough (more common with ACE inhibitors than ARBs)
Important Caveats:
- Do not use ACE inhibitors/ARBs during acute phase of HSPN with rapidly changing kidney function 3
- Avoid in patients with severe acute kidney injury
- Use caution in adolescent females of childbearing potential (teratogenic potential)
- Normalize proteinuria to body surface area to account for growth in children 1
Adjunctive Therapies:
- Sodium restriction to enhance antiproteinuric effects 1, 4
- Fish oil supplementation may provide additional benefit (1 g twice daily) 5
- Consider lipid-lowering therapy if persistent hyperlipidemia
Long-term Management
- Continue ACE inhibitor/ARB therapy for at least 12 months after achieving remission
- Gradually taper medication if proteinuria resolves completely
- Monitor for relapse after medication discontinuation
- Consider repeat kidney biopsy if proteinuria persists despite optimal therapy
The evidence strongly supports using ACE inhibitors or ARBs as first-line therapy for children with HSPN and persistent proteinuria, with escalation to immunosuppressive therapy for those who fail to respond adequately.