What is the treatment for proteinuria?

Treatment of Proteinuria

Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are the first-line treatment for proteinuria, titrated to the maximum tolerated dose to achieve optimal reduction of proteinuria. 1

Assessment and Risk Stratification

Before initiating treatment, it's essential to:

1. Determine the severity of proteinuria:

   • Low risk: Normal renal function, proteinuria <1 g/day
   • Medium risk: Proteinuria 1-8 g/day
   • High risk: Proteinuria >8 g/day or deteriorating renal function 2

2. Identify the underlying cause through:

   • Quantification of proteinuria (24-hour collection or protein-to-creatinine ratio)
   • Assessment of renal function (eGFR)
   • Evaluation for secondary causes (diabetes, hypertension, glomerulonephritis)

Treatment Algorithm

First-Line Therapy

1. For proteinuria >0.5 g/day:

   • Start ACEi or ARB therapy 2, 1
   • Initial dosing: For ARBs like losartan, start at 50 mg once daily 3
   • Titrate upward to maximum tolerated dose to achieve proteinuria <1 g/day 1

2. Blood pressure targets:

   • Proteinuria >1 g/day: <125/75 mmHg
   • Proteinuria <1 g/day: <130/80 mmHg 1

Monitoring and Dose Adjustment

• Check serum creatinine and potassium 1-2 weeks after initiation or dose increase 1
• Acceptable initial increase in serum creatinine: up to 30% 1
• Continue monitoring every 3 months initially 1
• Target cyclosporin blood levels (if used): C0 = 125-175 ng/ml 2

Response Assessment

• Target goals:

  • 25% reduction in proteinuria at 3 months
  • 50% reduction at 6 months
  • <500-700 mg/g at 12 months 1

• If complete remission occurs: Taper medication slowly over 3-4 months

• If partial remission occurs: Continue therapy for 1-2 years 2

• If no response after 3-6 months at maximum tolerated dose: Consider alternative therapy 2

Special Considerations

For Diabetic Nephropathy

Losartan has proven efficacy in diabetic nephropathy with:

• 16% risk reduction in the composite endpoint of doubling serum creatinine, ESRD, or death
• 25% reduction in doubling of serum creatinine
• 29% reduction in ESRD
• 34% average reduction in proteinuria 3

For Resistant Cases

For patients with persistent nephrotic-range proteinuria despite maximum conservative therapy:

1. Consider cyclosporin therapy:

   • Initial dose: 3-4 mg/kg/day (twice daily dosing)
   • Duration: At least 6 months
   • Target: 50% reduction in proteinuria within 6 months 2

2. Alternative immunosuppressive options:

   • Cytotoxic agents + corticosteroids for specific glomerular diseases 2

Lifestyle Modifications

• Restrict dietary sodium to <2.0 g/day
• Maintain protein intake at approximately 0.8 g/kg/day
• Normalize weight if overweight or obese
• Consider plant-based protein sources rather than animal proteins 1

Management of Complications

• Treat hyperlipidemia with statins, particularly in patients with other cardiovascular risk factors
• Treat metabolic acidosis if serum bicarbonate <22 mmol/L
• For nephrotic syndrome with edema, initiate treatment with loop diuretics 1

Important Caveats

• Temporary suspension of ACEi/ARB is recommended during episodes of dehydration or "sick days" 1
• Permanently discontinue if renal function continues to deteriorate or if refractory hyperkalemia develops 1
• Avoid ACEi/ARB in pregnancy (category D/X) 1
• Do not prematurely discontinue therapy due to modest increases in serum creatinine, as the antiproteinuric effect may take 3-6 months to fully manifest 1
• Proteinuria >3.8 g/day carries a 35% risk of end-stage renal disease within 2 years, compared to only 4% risk for proteinuria <2.0 g/day 2

By following this structured approach to treating proteinuria, you can significantly reduce the risk of progression to end-stage renal disease and improve patient outcomes.