What are the first-line antiproteinuric (Anti-Proteinuria) medications for patients with proteinuria?

First-Line Antiproteinuric Medications

ACE inhibitors (ACEi) or Angiotensin II Receptor Blockers (ARBs) are the first-line antiproteinuric medications for patients with proteinuria, and should be titrated to maximally tolerated doses. 1, 2

Indications Based on Proteinuria Severity

• For proteinuria ≥1 g/day: Long-term ACEi or ARB treatment is strongly recommended (1B evidence) with up-titration of the drug depending on blood pressure 1
• For proteinuria between 0.5-1 g/day: ACEi or ARB treatment is suggested (2D evidence) 1
• ACEi or ARB should be titrated upwards as far as tolerated to achieve proteinuria <1 g/day (2C evidence) 1

Blood Pressure Targets with Antiproteinuric Therapy

• For patients with proteinuria <1 g/day: Target blood pressure of 130/80 mmHg 1
• For patients with proteinuria ≥1 g/day: More intensive blood pressure control with target of 125/75 mmHg 1
• Current guidelines recommend targeting systolic blood pressure <120 mmHg in most adult patients using standardized office BP measurement 1

Optimizing Antiproteinuric Effect

• Restrict dietary sodium to <2.0 g/day to enhance the antiproteinuric effects of RAS blockade 1, 2
• Do not stop ACEi or ARB with modest and stable increase in serum creatinine (up to 30%) as this is an expected effect of these medications 1, 2
• Stop ACEi or ARB only if kidney function continues to worsen or refractory hyperkalemia develops 1
• Use potassium-wasting diuretics and/or potassium-binding agents to manage hyperkalemia when using RAS blockers 1, 2

Management of Resistant Proteinuria

• For persistent proteinuria despite maximally tolerated ACEi or ARB therapy, consider:
  • Intensifying dietary sodium restriction 1, 2
  • Adding mineralocorticoid receptor antagonists (monitor for hyperkalemia) 1
  • Combination therapy with both ACEi and ARB in selected young adults without comorbidities 1, 3

Special Considerations

• For IgA nephropathy with persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care (including ACEi/ARB) and GFR ≥50 ml/min/1.73 m², consider adding a 6-month course of corticosteroid therapy 1
• For patients with podocytopathy (MCD, FSGS) expected to be rapidly responsive to immunosuppression, it may be reasonable to delay initiation of ACEi or ARB if they don't have hypertension 1
• In diabetic nephropathy with proteinuria, losartan has been shown to significantly reduce proteinuria by an average of 34% within 3 months of starting therapy 4

Monitoring and Follow-up

• Monitor serum creatinine, potassium levels, and proteinuria frequently when on ACEi or ARB therapy 1, 2
• Counsel patients to hold ACEi or ARB and diuretics when at risk for volume depletion (illness, diarrhea, etc.) 1, 2
• Evidence of improvement in proteinuria should be noted by 3 months, with at least 50% reduction in proteinuria expected by 6 months 2, 5

Comparative Efficacy

• ACEi and ARBs reduce proteinuria to a similar degree when used as monotherapy 6
• Combination therapy with ACEi and ARB further reduces proteinuria compared to either agent alone (ratio of means for combination vs. monotherapy: 0.75-0.82) 6, 7
• The antiproteinuric effect of RAS blockade is consistent across different levels of proteinuria and underlying diseases 6