What is the treatment for proteinuria?

Treatment of Proteinuria

Start with an ACE inhibitor or ARB uptitrated to the maximum tolerated dose as first-line therapy, combined with blood pressure control targeting systolic BP <120-130 mmHg and dietary sodium restriction to <2.0 g/day. 1, 2

First-Line Pharmacologic Therapy

Renin-angiotensin system (RAS) blockade is the cornerstone of proteinuria management. 1, 2

• Initiate an ACE inhibitor or ARB and uptitrate to the maximum tolerated or allowed daily dose, not merely the dose that achieves blood pressure targets, as the antiproteinuric effect extends beyond blood pressure reduction alone. 1, 2
• Do not discontinue ACE inhibitor or ARB therapy if serum creatinine increases modestly and remains stable (up to 30% elevation), as this is an expected hemodynamic effect. 1, 2
• Monitor laboratory values (serum creatinine, potassium, proteinuria) frequently during uptitration. 1
• Counsel patients to temporarily hold ACE inhibitor/ARB and diuretics during periods of volume depletion risk (illness, diarrhea, vomiting). 1

Blood Pressure Targets

Target systolic blood pressure of 120-130 mmHg using standardized office measurements in most patients with proteinuria. 1, 2

• For patients with persistent proteinuria >1 g/day, aim for blood pressure ≤125/75 mmHg. 1
• Achieving these lower blood pressure targets typically requires multiple antihypertensive agents in addition to RAS blockade. 3

Dietary and Lifestyle Modifications

Restrict dietary sodium to <2.0 g/day (<90 mmol/day) in all patients with proteinuria, as this enhances the antiproteinuric effects of pharmacologic therapy. 1, 2

• Intensify sodium restriction further if proteinuria fails to respond adequately to maximal medical therapy. 1
• Implement weight normalization, smoking cessation, and regular exercise as synergistic interventions. 1
• Treat metabolic acidosis (serum bicarbonate <22 mmol/L) to optimize therapeutic response. 1

Management of Treatment-Resistant Proteinuria

For patients who fail to achieve adequate proteinuria reduction on maximally tolerated ACE inhibitor/ARB therapy:

• Consider adding mineralocorticoid receptor antagonists (spironolactone or eplerenone), monitoring closely for hyperkalemia. 1
• Use potassium-wasting diuretics and/or potassium-binding agents to maintain normal serum potassium levels, allowing continuation of RAS blockade. 1
• Ensure strict adherence to sodium restriction <2.0 g/day. 1

Immunosuppressive Therapy Considerations

For persistent proteinuria >1 g/day despite 3-6 months of optimized supportive care (maximal RAS blockade, blood pressure control, sodium restriction), consider disease-specific immunosuppressive therapy. 1, 2

IgA Nephropathy

• Consider a 6-month course of corticosteroid therapy if proteinuria persists >1 g/day and GFR >50 ml/min/1.73 m². 1, 2

Lupus Nephritis with Nephrotic-Range Proteinuria

• Initiate combined immunosuppressive treatment with glucocorticoids plus mycophenolic acid analogs (target dose 2-3 g/day) or low-dose intravenous cyclophosphamide (500 mg every 2 weeks for 6 doses). 3
• Alternative regimens include combination of mycophenolic acid (1-2 g/day) with a calcineurin inhibitor (particularly tacrolimus) for nephrotic-range proteinuria. 3
• Use pulse intravenous methylprednisolone (500-2500 mg total) followed by oral prednisone (0.3-0.5 mg/kg/day) tapered to ≤7.5 mg/day by 3-6 months to reduce cumulative glucocorticoid exposure. 3

Pure Class V Lupus Nephritis

• For nephrotic-range proteinuria, use mycophenolic acid (2-3 g/day) combined with pulse methylprednisolone followed by oral prednisone (20 mg/day, tapered to ≤5 mg/day by 3 months). 3
• Alternative options include calcineurin inhibitors (especially tacrolimus) in monotherapy or combined with mycophenolic acid. 3

Monitoring and Treatment Goals

Evidence of proteinuria improvement should be apparent by 3 months, with at least 50% reduction by 6 months. 1

• Target proteinuria reduction of ≥25% by 3 months, ≥50% by 6 months, and UPCR <500-700 mg/g by 12 months (complete clinical response). 3
• Patients with nephrotic-range proteinuria at baseline may require an additional 6-12 months to achieve complete response; avoid premature therapy switches if proteinuria is steadily improving. 3
• If no response occurs after 6 months of optimal therapy, consider kidney biopsy (if not already performed) to guide further management. 3

Critical Pitfalls to Avoid

• Do not stop ACE inhibitor/ARB prematurely with modest creatinine increases up to 30% unless kidney function continues to deteriorate or refractory hyperkalemia develops. 1, 2
• Do not delay immunosuppression in appropriate candidates with persistent significant proteinuria despite optimal supportive care for 3-6 months. 2
• Do not undertitrate RAS blockade—the goal is maximum tolerated dose, not simply blood pressure control. 1, 2
• Do not neglect sodium restriction—pharmacologic therapy is substantially less effective without dietary sodium limitation to <2.0 g/day. 1, 2