How is proteinuria managed or treated?

Management of Proteinuria

The cornerstone of proteinuria management is the use of ACE inhibitors or ARBs titrated to maximum tolerated doses to achieve a target proteinuria reduction of <1 g/day, with blood pressure goals of <125/75 mmHg for proteinuria >1 g/day and <130/80 mmHg for proteinuria <1 g/day. 1

Assessment and Risk Stratification

• Quantify proteinuria using spot urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) to determine severity:

  • Low risk: <1 g/day
  • Medium risk: 1-8 g/day
  • High risk: >8 g/day or deteriorating renal function 1

• Determine if proteinuria is:

  • Glomerular (usually >2 g/day)
  • Tubular
  • Overflow 2

Treatment Algorithm

First-Line Therapy

1. ACE inhibitors or ARBs:

   • Start for proteinuria >0.5 g/day
   • Titrate to maximum tolerated dose
   • Goal: Reduce proteinuria to <1 g/day 1
   • Monitor:
     • Check serum creatinine and potassium 1-2 weeks after initiation or dose increase
     • Accept initial increase in serum creatinine up to 30%
     • Continue monitoring every 3 months 1

2. Blood pressure control:

   • Target <125/75 mmHg for proteinuria >1 g/day
   • Target <130/80 mmHg for proteinuria <1 g/day 1

3. Treatment goals:

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

Supportive Measures

• Dietary modifications:

  • Sodium restriction: <2.0 g/day
  • Protein intake: approximately 0.8 g/kg/day 1
  • Weight normalization if overweight/obese 1

• Metabolic management:

  • Treat metabolic acidosis if serum bicarbonate <22 mmol/L
  • Consider statin therapy for hyperlipidemia 1

Nephrology Referral Criteria

Refer to nephrology if:

• Persistent proteinuria >1 g/day (ACR ≥60 mg/mmol or PCR ≥100 mg/mmol), as renal biopsy and immunosuppressive medications may be needed 3
• GFR <30 mL/min/1.73 m² (unless stable GFR with clear diagnosis or limited life expectancy) 3
• Abrupt sustained decrease in eGFR >20% after excluding reversible causes 3
• Inability to tolerate renoprotective medications 3
• Uncertainty about diagnosis 3
• Risk of kidney failure within 1 year is 10-20% or higher 3

Special Considerations

Lupus Nephritis

• For isolated membranous lupus nephritis (class V):

  • Treatment depends on proteinuria level
  • Universal immunosuppression for nephrotic syndrome
  • For subnephrotic proteinuria >1 g/day, consider immunosuppression despite maximal supportive therapy 3

• Response definitions:

  • Complete response: Proteinuria <0.5 g/day
  • Partial response: ≥50% reduction in proteinuria to subnephrotic levels
  • No response: Failure to achieve partial response 3

Diabetic Nephropathy

• Losartan has demonstrated significant benefits in diabetic nephropathy:
  • 16% risk reduction in composite endpoint of doubling serum creatinine, ESRD, or death
  • 25% reduction in doubling of serum creatinine
  • 29% reduction in ESRD
  • 34% reduction in proteinuria 4

Common Pitfalls to Avoid

• Discontinuing ACEi/ARB prematurely: Don't stop therapy due to modest increases in serum creatinine (up to 30% increase is acceptable) 1

• Failing to counsel patients: Instruct patients to hold ACEi/ARB and diuretics during periods of volume depletion (sick days) 1

• Overlooking cardiovascular risk: Proteinuria is an independent risk factor for cardiovascular morbidity and mortality 1

• Inadequate monitoring: Regular follow-up of serum creatinine, potassium, and proteinuria is essential to ensure treatment efficacy and safety 1

• Delaying nephrology referral: Early referral is crucial for patients with persistent proteinuria >1 g/day or GFR <30 mL/min/1.73 m² 3