What is the management and treatment of proteinuria?

Management and Treatment of Proteinuria

The management of proteinuria should begin with ACE inhibitors or ARBs titrated to maximum tolerated dose, with a target blood pressure of <125/75 mmHg for patients with proteinuria >1 g/day to reduce morbidity and mortality. 1

Initial Assessment and Classification

• Assess risk of progression by evaluating:

  • Degree of proteinuria (quantified as g/day or protein-to-creatinine ratio)
  • Blood pressure
  • eGFR at diagnosis and during follow-up 2
  • Pathological features when available 2

• Determine underlying cause:

  • Glomerular proteinuria (>2 g/day): Most common pathological type
  • Tubular proteinuria: Consider in appropriate clinical context
  • Overflow proteinuria: Rare, seen in conditions like multiple myeloma

First-Line Treatment: Renin-Angiotensin System Blockade

1. ACE inhibitors or ARBs:

   • Start and titrate to maximum tolerated dose 1
   • Monitor serum creatinine and potassium within 1-2 weeks of initiation and with each dose increase 1
   • Target blood pressure <125/75 mmHg for proteinuria >1 g/day 2, 1
   • For IgA nephropathy with proteinuria, target <130/80 mmHg if proteinuria <1 g/day and <125/75 mmHg if >1 g/day 2

2. Losartan has demonstrated specific benefits:

   • Reduces proteinuria by an average of 34%, evident within 3 months of starting therapy 3
   • Slows decline in glomerular filtration rate by 13% 3
   • Reduces risk of doubling serum creatinine by 25% and ESRD by 29% in diabetic nephropathy 3

Dietary and Lifestyle Modifications

• Sodium restriction: <2.0 g/day (<90 mmol/day) to enhance antiproteinuric effects of RAS blockade 1
• Protein restriction: Consider in consultation with dietitian, particularly in advanced CKD
• Weight normalization: Reduce obesity to improve proteinuria 1
• Smoking cessation: Essential for kidney protection 1
• Regular exercise: Recommended as part of comprehensive management 1

Management of Treatment-Resistant Proteinuria

If proteinuria persists ≥1 g/day despite 3-6 months of optimized supportive care:

1. Verify medication adherence and adequate dosing of ACE inhibitors/ARBs 1

2. Consider combination therapy:

   • ACE inhibitor plus ARB may provide additional antiproteinuric effect
   • Monitor serum potassium and renal function closely 1

3. Consider immunosuppressive therapy based on underlying cause:

   • For IgA nephropathy: 6-month course of corticosteroids if GFR >50 ml/min/1.73m² 2
   • For lupus nephritis: Mycophenolate mofetil/mycophenolic acid (MMF/MPA) or low-dose cyclophosphamide as first-line options 2
   • For crescentic glomerulonephritis: Steroids and cyclophosphamide 2

4. Fish oil supplementation:

   • Consider for IgA nephropathy with persistent proteinuria >1 g/day 2

Special Considerations

1. Pregnancy:

   • Compatible medications (HCQ, prednisone, azathioprine, tacrolimus) can be continued 2
   • MMF/MPA should be withdrawn 3-6 months before conception 2
   • Use acetylsalicylic acid to reduce pre-eclampsia risk 2
   • Monitor every 4 weeks with multidisciplinary team 2

2. Pediatric patients:

   • Management principles similar to adults 2
   • ACE inhibitors and ARBs have largest evidence base for efficacy and safety 2
   • Target 24-hour mean arterial pressure ≤50th percentile for age, sex, and height 2
   • Ensure coordinated transition to adult specialists 2

Monitoring Response

• Proteinuria goal varies by underlying condition:

  • Complete clinical response: <0.5-0.7 g/24 hours by 12 months 2
  • Partial clinical response: At least 50% reduction in proteinuria by 6 months 2
  • For nephrotic-range proteinuria at baseline, timeframes may be extended by 6-12 months 2

• Monitor for adverse effects:

  • Hyperkalemia with ACE inhibitors/ARBs
  • Acute kidney injury, especially during intercurrent illness
  • Hold RAS inhibitors and diuretics during acute illness with risk of volume depletion 2, 1

Common Pitfalls to Avoid

1. Premature treatment changes before allowing adequate time for response (at least 3-6 months)
2. Inadequate dosing of ACE inhibitors/ARBs
3. Failure to address dietary sodium intake
4. Not holding RAS inhibitors during acute illness with volume depletion
5. Overlooking the need for prophylactic measures in immunosuppressed patients (pneumococcal vaccine, influenza vaccine, TB screening)

By following this algorithmic approach to proteinuria management, focusing on RAS blockade, blood pressure control, and appropriate immunosuppression when indicated, progression to end-stage kidney disease can be significantly reduced, improving long-term morbidity and mortality outcomes.