When to Start ACE Inhibitors in Proteinuria
Start an ACE inhibitor immediately in any patient with proteinuria ≥1 g/day, regardless of blood pressure status, and strongly consider starting if proteinuria is between 0.5-1 g/day. 1
Primary Indications for ACE Inhibitor Initiation
Strong Indication (Start Immediately)
- Proteinuria ≥1 g/day: This is a firm recommendation requiring long-term ACE inhibitor or ARB treatment with uptitration based on blood pressure tolerance 1
- Hypertension + any level of proteinuria: Use ACE inhibitor or ARB to maximally tolerated dose as first-line therapy 1
Moderate Indication (Strongly Consider)
- Proteinuria 0.5-1 g/day: ACE inhibitor or ARB treatment is suggested even without hypertension 1
- In children: Consider if proteinuria is 0.5-1 g/day per 1.73 m² 1
Critical Exception: When to Delay or Avoid
Do NOT start ACE inhibitors in patients presenting with abrupt onset nephrotic syndrome, particularly if minimal change disease (MCD) is suspected, as these drugs can cause acute kidney injury in this setting. 1
Additional contraindications include:
- Rapidly changing kidney function without immunosuppression 1
- Patients expected to be rapidly responsive to immunosuppression (MCD, steroid-sensitive nephrotic syndrome, FSGS) without hypertension—delay may be reasonable 1
Dosing Strategy
Uptitrate to maximally tolerated or allowed dose, not just to blood pressure control 1:
- Start at standard doses and increase progressively 1
- The goal is proteinuria reduction to <1 g/day, not just blood pressure control 1
- Continue uptitration even if blood pressure is controlled 1
Blood Pressure Targets When Using ACE Inhibitors
- Target systolic BP <120 mmHg in most adult patients with proteinuria using standardized office measurement 1, 2
- In IgA nephropathy specifically: 130/80 mmHg if proteinuria <1 g/day; 125/75 mmHg if proteinuria ≥1 g/day 1
- In children: Target 24-hour mean arterial pressure at 50th percentile for age, sex, and height 1
Essential Monitoring Parameters
Accept up to 30% increase in serum creatinine after starting ACE inhibitor—this is hemodynamic and expected, NOT a reason to stop therapy. 1, 2, 3
Stop ACE inhibitor only if:
- Check labs every 2-4 weeks initially
- Assess serum creatinine, eGFR, potassium, and urine protein-to-creatinine ratio
Synergistic Supportive Measures
Dietary sodium restriction to <2.0 g/day (<90 mmol/day) is mandatory, as it enhances the antiproteinuric effect of ACE inhibitors 1, 2, 4, 3
Additional lifestyle modifications 1:
- Weight normalization
- Smoking cessation
- Regular exercise
Managing Resistant Proteinuria
If proteinuria persists despite maximized ACE inhibitor dose 1, 4:
- Add thiazide-like diuretic for synergistic effect
- Consider mineralocorticoid receptor antagonist (spironolactone 25-50 mg) with careful potassium monitoring
- In diabetic patients, add SGLT2 inhibitor for additive renoprotection 2, 4
Common Pitfalls to Avoid
The most common error is discontinuing ACE inhibitors prematurely due to modest creatinine elevation—this removes critical renoprotection. 2, 3 The initial rise in creatinine up to 30% is hemodynamic and acceptable 1, 2, 3.
Do not combine ACE inhibitor with ARB, as this increases adverse effects without additional benefit in most patients 2. The exception is young adults where combination may be considered 1.
Counsel patients to hold ACE inhibitors during intercurrent illnesses with risk of volume depletion (vomiting, diarrhea, fever) 1, 2.
Timeline for Reassessment
- Optimize ACE inhibitor therapy for 3-6 months before considering additional immunosuppressive therapy 1
- This allows adequate time to assess antiproteinuric response 1
- If proteinuria remains >1 g/day after 3-6 months of optimized supportive care with preserved GFR ≥50 mL/min/1.73 m², consider adding immunosuppression 1