What is the treatment for proteinuria?

Treatment of Proteinuria

The first-line treatment for proteinuria is angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), which should be titrated to the maximum tolerated dose to achieve proteinuria reduction below 1 g/day. 1, 2

Assessment and Classification

• Proteinuria exceeding 150 mg/day is considered abnormal and requires evaluation to determine the underlying cause 3
• Risk assessment should include measurement of proteinuria level, blood pressure, and estimated glomerular filtration rate (eGFR) at diagnosis and during follow-up 1
• Proteinuria >1 g/day is associated with faster progression of kidney disease and poorer prognosis 4

Treatment Based on Proteinuria Level

For proteinuria between 0.5-1 g/day:

• ACEi or ARB therapy is suggested even at this lower level of proteinuria 1
• Target blood pressure <130/80 mmHg 1, 2
• Regular monitoring of kidney function and proteinuria every 3-6 months 2

For proteinuria >1 g/day:

• Long-term ACEi or ARB treatment is strongly recommended with uptitration depending on blood pressure 1
• Target blood pressure <125/75 mmHg 1
• Titrate ACEi or ARB upward as far as tolerated to achieve proteinuria <1 g/day 1
• If proteinuria persists >1 g/day despite 3-6 months of optimized supportive care and GFR >50 ml/min/1.73 m², consider a 6-month course of corticosteroid therapy 1

For nephrotic-range proteinuria:

• Combined immunosuppressive treatment with glucocorticoids and another agent (mycophenolic acid analogs, cyclophosphamide) may be necessary depending on underlying cause 1
• Manage complications such as thrombosis, dyslipidemia, and edema 1

Disease-Specific Approaches

For Lupus Nephritis:

• Initial therapy with corticosteroids combined with either cyclophosphamide or mycophenolate mofetil 1
• Treatment aims for reduction in proteinuria of at least 25% by 3 months, 50% by 6 months, and a urine protein-to-creatinine ratio target below 500-700 mg/g by 12 months 1
• Hydroxychloroquine should be co-administered 1

For IgA Nephropathy:

• ACEi or ARB as first-line therapy 1
• Consider fish oil for persistent proteinuria >1 g/day despite optimized supportive care 1
• Corticosteroid therapy may be considered if proteinuria persists despite supportive care 1

For Class V Lupus Nephritis (membranous):

• Combined immunosuppressive treatment with glucocorticoids plus either mycophenolic acid analogs, cyclophosphamide, or calcineurin inhibitors 1
• Triple immunosuppression with glucocorticoids, tacrolimus, and low-dose mycophenolic acid may be more effective than standard therapy 1

Practical Considerations

• Monitor serum creatinine and potassium frequently when using ACEi or ARB 1
• Do not stop ACEi or ARB with modest and stable increases in serum creatinine (up to 30%) 1
• Stop ACEi or ARB if kidney function continues to worsen or if refractory hyperkalemia develops 1
• Counsel patients to temporarily hold ACEi/ARB and diuretics when at risk for volume depletion (e.g., during illness with vomiting or diarrhea) 1
• Employ lifestyle modifications including sodium restriction (<2.0 g/day), weight normalization, smoking cessation, and regular exercise 1

Common Pitfalls

• Not accounting for the lag between treatment initiation and reduction in proteinuria, which can lead to premature treatment changes 2
• Initiating immunosuppressive therapy in patients with advanced kidney disease (eGFR ≤30 ml/min/1.73 m²) where risks may outweigh benefits 1, 2
• Starting ACEi/ARB in patients with abrupt onset of nephrotic syndrome, which can cause acute kidney injury especially in minimal change disease 1
• Not addressing other modifiable risk factors such as hypertension, diabetes control, and smoking 2

Remember that proteinuria is not just a marker of kidney disease but may also contribute directly to kidney damage, making its reduction an important therapeutic goal 4.