What is the treatment for proteinuria?

Treatment of Proteinuria

The first-line treatment for proteinuria is ACE inhibitors or ARBs, which should be titrated to the maximum tolerated dose to achieve a target proteinuria reduction of less than 1 g/day. 1

Initial Assessment and Classification

• Determine the severity of proteinuria:

  • Mild: 0.5-1 g/day
  • Moderate: 1-3.5 g/day
  • Severe/nephrotic: >3.5 g/day

• Identify underlying cause through:

  • Kidney biopsy (when proteinuria ≥0.5 g/day with unexplained decrease in GFR) 1
  • Assessment of activity and chronicity indices 1

Treatment Algorithm Based on Proteinuria Level

For Proteinuria 0.5-1 g/day:

1. Start ACE inhibitor or ARB therapy 1
2. Target blood pressure <130/80 mmHg 1
3. Dietary sodium restriction to <2 g/day 2

For Proteinuria >1 g/day:

1. ACE inhibitor or ARB therapy titrated to maximum tolerated dose 1
2. Target blood pressure <125/75 mmHg 1, 2
3. Dietary interventions:
   • Sodium restriction to <2 g/day
   • Protein restriction to 0.6-0.8 g/kg/day 2
   • Consider plant-based protein sources over animal proteins 2

For Nephrotic-Range Proteinuria (>3.5 g/day):

1. Continue ACE inhibitor or ARB therapy
2. Consider immunosuppressive therapy based on underlying cause 1
3. Add loop diuretics for edema management 2
4. Consider treatment for hyperlipidemia, particularly in patients with other cardiovascular risk factors 2

Specific Treatment Based on Underlying Cause

For Membranous Nephropathy:

• If proteinuria <3.5 g/day and serum albumin >30 g/L: supportive care only
• If proteinuria >3.5 g/day or complications present: consider rituximab, cyclophosphamide with glucocorticoids, or tacrolimus-based therapy 1

For IgA Nephropathy:

• For persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care and GFR >50 ml/min/1.73 m²: add 6-month course of corticosteroid therapy 1
• Consider fish oil for persistent proteinuria ≥1 g/day despite optimized supportive care 1

For Lupus Nephritis:

• Class III or IV (±V): MMF (2-3 g/day) or low-dose intravenous cyclophosphamide with glucocorticoids 1
• Pure class V with nephrotic-range proteinuria: MMF (2-3 g/day) with glucocorticoids 1

Monitoring Response to Treatment

• Assess proteinuria reduction:
  • Target 25% reduction by 3 months
  • Target 50% reduction by 6 months
  • Target <500-700 mg/g by 12 months 1
• Patients with nephrotic-range proteinuria may require 6-12 additional months to reach complete response 1

Evidence for ACE Inhibitors/ARBs

Losartan has been shown to significantly reduce proteinuria by an average of 34% within 3 months of starting therapy and slow the rate of decline in GFR by 13% in patients with type 2 diabetes with nephropathy 3. The RENAAL study demonstrated that losartan reduced the risk of doubling serum creatinine by 25% and end-stage renal disease by 29% compared to placebo 3.

Pitfalls and Caveats

1. Avoid immunosuppressive therapy in patients with GFR <30 ml/min/1.73 m² unless there is rapidly deteriorating kidney function 1

2. Monitor for hyperkalemia and acute kidney injury when initiating or uptitrating ACE inhibitors or ARBs

3. Recognize that persistent proteinuria despite disappearance of disease-specific antibodies (e.g., anti-PLA2R in membranous nephropathy) may indicate secondary focal segmental glomerulosclerosis 1

4. In patients with resistant disease, check medication compliance and monitor efficacy markers (e.g., B-cell response for rituximab, drug levels for calcineurin inhibitors) 1

5. Consider referral to nephrology when proteinuria exceeds 1 g/day (ACR ≥60 mg/mmol or PCR ≥100 mg/mmol) as renal biopsy and immunosuppressive medications may be indicated 1

By following this structured approach to treating proteinuria, you can significantly improve outcomes related to kidney function preservation, cardiovascular risk reduction, and quality of life for patients with proteinuric kidney diseases.