What is the management of proteinuria?

Management of Proteinuria

The management of proteinuria should focus on renin-angiotensin system blockade with ACE inhibitors or ARBs as first-line therapy, along with blood pressure control targeting <120 mmHg systolic, and appropriate disease-specific immunosuppression when indicated. 1

Initial Assessment and Classification

• Proteinuria is defined as urinary protein excretion exceeding 300 mg/24 hours and requires proper quantification and classification to guide management 2
• Classify proteinuria based on severity:
  • Low-level proteinuria: <1 g/day
  • Nephrotic-range proteinuria: >3 g/day 1, 3
• Determine underlying cause through kidney biopsy when proteinuria is persistent (≥0.5 g/24 hours) or when there's unexplained decrease in GFR 1

General Management Principles

Blood Pressure Control

• Target systolic blood pressure <120 mmHg using standardized office BP measurement in adults 1
• In children, target 24-hour mean arterial pressure at ≤50th percentile for age, sex, and height by ambulatory blood pressure monitoring 1
• Uptitrate ACEi or ARB to maximally tolerated dose as first-line therapy for proteinuria 1

Renin-Angiotensin System Blockade

• ACEi or ARBs should be used at maximally tolerated doses as first-line therapy for both hypertension and proteinuria 1, 4
• Losartan has demonstrated significant reduction in proteinuria by an average of 34% within 3 months and slowed decline in glomerular filtration rate by 13% 4
• Counsel patients to temporarily discontinue RAS inhibitors and diuretics during periods of volume depletion (intercurrent illness) 1

Management of Edema

• Use diuretics as preferred agents for edema management, along with dietary sodium restriction 1
• Consider adding mechanistically different diuretics if response is insufficient, while monitoring for adverse effects (hyponatremia, hypokalemia, GFR reduction) 1

Disease-Specific Management

Lupus Nephritis

• For class III or IV (±V) lupus nephritis:

  • Combine immunosuppressives with glucocorticoids 1
  • First-line options include MMF (2-3 g/day) or low-dose intravenous cyclophosphamide (500 mg every 2 weeks for 6 doses) 1
  • Consider combination of MMF with calcineurin inhibitors (especially tacrolimus) for nephrotic-range proteinuria 1

• For pure class V lupus nephritis with nephrotic-range proteinuria:

  • MMF (2-3 g/day) with pulse IV methylprednisolone followed by oral prednisone is recommended 1
  • Alternative options include IV cyclophosphamide or calcineurin inhibitors (especially tacrolimus) 1

• Treatment goals:

  • Reduction in proteinuria of at least 25% by 3 months
  • 50% reduction by 6 months
  • Target UPCR below 500-700 mg/g by 12 months 1
  • Patients with nephrotic-range proteinuria may require additional 6-12 months to reach complete response 1

Other Glomerular Diseases

• For primary glomerular diseases with proteinuria, optimize supportive care first 1
• Consider disease-specific immunosuppression based on biopsy findings and clinical presentation 1
• For nephrotic syndrome, monitor and treat complications (thrombosis, dyslipidemia, edema) 1

Additional Management Considerations

Dyslipidemia Management

• Consider statin therapy for persistent dyslipidemia, particularly in patients with other cardiovascular risk factors 1
• Start with statins as first-line therapy and consider non-statin therapy (bile acid sequestrants, fibrates, ezetimibe) if goals aren't achieved 1

Thrombosis Prevention

• Full anticoagulation is indicated for patients with thromboembolic events occurring in nephrotic syndrome 1
• Consider prophylactic anticoagulation in high-risk nephrotic syndrome patients when thromboembolism risk exceeds bleeding risk 1

Dietary Modifications

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) 1
• Consider protein restriction in certain cases of proteinuria to slow progression of renal disease 5
• Intensify dietary sodium restriction in patients who fail to achieve proteinuria reduction despite maximal medical therapy 1

Infection Prevention

• Administer pneumococcal vaccine to patients with nephrotic syndrome and/or CKD 1
• Ensure patients and household contacts receive influenza vaccine 1
• Consider prophylactic trimethoprim-sulfamethoxazole in patients receiving high-dose immunosuppression 1

Monitoring and Follow-up

• Monitor labs frequently if on ACEi or ARB therapy 1
• Consider referral to nephrology if proteinuria persists >1 g/day (ACR ≥60 mg/mmol or PCR ≥100 mg/mmol) as renal biopsy may be indicated 1
• Timely referral for planning renal replacement therapy in people with progressive CKD when risk of kidney failure within 1 year is 10-20% or higher 1

Special Considerations

• In pregnancy, acetylsalicylic acid is recommended to reduce pre-eclampsia risk in patients with proteinuria 1
• Pregnant patients should be assessed at least every 4 weeks, preferably by a multidisciplinary team 1
• In children, lupus nephritis is often more severe with increased damage accrual; management principles are similar to adults but require coordinated transition programs to adult specialists 1