What is the management and treatment of proteinuria?

Management and Treatment of Proteinuria

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are the first-line therapy for proteinuria, titrated to maximally tolerated doses to reduce proteinuria to <1 g/day. 1

Assessment and Classification of Proteinuria

Proteinuria is a hallmark of kidney disease and can be categorized based on severity and mechanism:

• Mild proteinuria: <1 g/day
• Moderate proteinuria: 1-3 g/day
• Severe proteinuria: >3 g/day

Mechanisms of proteinuria include:

• Glomerular: Most common cause of significant proteinuria (>2 g/day)
• Tubular: Results from impaired reabsorption of normally filtered proteins
• Overflow: Occurs when plasma proteins exceed the reabsorptive capacity of tubules

First-Line Treatment

RAAS Blockade with ACE Inhibitors or ARBs

ACE inhibitors and ARBs have the strongest evidence base for treating proteinuria:

• They reduce proteinuria through both BP-dependent and BP-independent mechanisms 1
• In patients with diabetic nephropathy, losartan significantly reduced proteinuria by an average of 34% within 3 months of starting therapy 2
• For children with proteinuria, ACE inhibitors or ARBs should be used as primary treatment 3

Dosing and Monitoring

1. Start with low dose of ACE inhibitor or ARB
2. Titrate to maximum tolerated dose to achieve maximum antiproteinuric effect
3. Monitor serum creatinine and potassium within 1-2 weeks after initiating or increasing dose
   • A modest increase in serum creatinine (up to 30%) is acceptable and expected 1
   • Discontinue if kidney function continues to worsen or if refractory hyperkalemia develops

Blood Pressure Targets

Blood pressure targets should be tailored based on proteinuria level:

• Proteinuria >1 g/day: Target BP <125/75 mmHg 1
• Proteinuria <1 g/day: Target BP <130/80 mmHg 1
• Pediatric patients: ≤50th percentile for age, sex, and height 1

Additional Pharmacological Strategies

If proteinuria persists despite maximum tolerated dose of ACE inhibitor or ARB:

1. Add a diuretic as second-line therapy for additional antiproteinuric effect 1

   • Diuretics should be used with caution as they may increase vasopressin levels and have deleterious effects on eGFR in some conditions like ADPKD 3

2. Consider non-dihydropyridine calcium channel blockers (diltiazem, verapamil) for additional antiproteinuric effect 1

   • Avoid dihydropyridine CCBs like amlodipine in patients with glomerular hypertension as they may exacerbate proteinuria 1

3. Consider dual RAAS blockade (ACE inhibitor + ARB) for resistant cases

   • This may provide additional proteinuria reduction but should be used cautiously due to increased risk of hyperkalemia and acute kidney injury 1
   • Evidence suggests dual RAAS blockade does not provide additional benefit over improved blood pressure control in some conditions like ADPKD 3

Non-Pharmacological Management

1. Sodium restriction: <2 g/day 1
2. Protein intake: Maintain at 0.8 g/kg/day (higher protein intake >1.3 g/kg/day is associated with increased proteinuria) 1
3. Diet recommendations: High in vegetables, fruits, whole grains, fiber, legumes, and plant-based proteins 1
4. Physical activity: Moderate-intensity exercise for at least 150 minutes per week 1
5. Weight normalization if overweight or obese 1

Monitoring Response to Treatment

• Check albumin:creatinine ratio every 3-6 months to assess treatment response 1
• Goal: Reduce proteinuria to <1 g/day or as low as possible 1
• Monitor blood pressure at every clinic visit 1
• Assess medication adherence at each visit 1

When to Refer to Nephrology

Refer patients to nephrology if they have:

• Persistent proteinuria >1 g/day despite treatment
• GFR <30 mL/min/1.73 m²
• Abrupt sustained decrease in eGFR >20%
• Inability to tolerate renoprotective medications
• Uncertainty about diagnosis
• Risk of kidney failure within 1 year is 10-20% or higher 1

Special Considerations

Children with Proteinuria

• Monitoring of proteinuria/albuminuria should be considered standard care for children with conditions like ADPKD 3
• Measure albumin/creatinine ratio in a laboratory rather than performing dipstick testing, which is less sensitive and specific 3
• Children with very-early-onset proteinuric kidney disease may have poorer outcomes 3

Diabetic Nephropathy

• In the RENAAL study, losartan treatment resulted in a 16% risk reduction in the primary composite endpoint (doubling of serum creatinine, ESRD, or death) 2
• Losartan reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% 2

Remember that proteinuria exceeding 1 g/day in patients with kidney disease indicates a poorer prognosis, and aggressive treatment is warranted to prevent progression to end-stage renal disease.