Treatment of Leukocytes and Protein in Urine
Treat the urinary tract infection first with empiric antibiotics, then reassess proteinuria after infection resolution to determine if ACE inhibitor or ARB therapy is needed for persistent proteinuria >0.5 g/day. 1, 2
Immediate Management: Treat the UTI
Diagnostic Steps
- Obtain urine culture before starting antibiotics to identify the causative pathogen and guide definitive therapy 1, 2
- The presence of leukocytes and nitrites strongly indicates active UTI requiring immediate treatment 1
- Quantify proteinuria using spot urine protein-to-creatinine ratio (PCR) or 24-hour collection to determine clinical significance (>0.5 g/day or PCR >500 mg/g) 1, 3
First-Line Antibiotic Options for Uncomplicated Cystitis
- Nitrofurantoin 100 mg twice daily for 5 days 1, 2, 4
- Fosfomycin trometamol 3 g single dose (women only) 1, 2, 4
- Pivmecillinam 400 mg three times daily for 3-5 days 2, 4
- Cefadroxil 500 mg twice daily for 3 days if local E. coli resistance <20% 2
- Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days only if local resistance patterns permit 2, 5
For Suspected Pyelonephritis (Fever, Flank Pain)
- Use oral fluoroquinolones or cephalosporins for 7-14 days 1, 3
- Adjust antibiotic dosing based on renal function 1
Post-Treatment Confirmation
- Repeat urinalysis after completing antibiotics to confirm UTI resolution and reassess proteinuria 1, 2, 3
- If symptoms persist or recur within 2 weeks, obtain repeat urine culture before retreating 2
Secondary Management: Address Persistent Proteinuria
When to Initiate Proteinuria Treatment
Do not attribute proteinuria solely to UTI if it persists after infection treatment 1—the combination of leukocyturia and proteinuria may indicate more severe noninfectious renal inflammation and worse kidney function 6
ACE Inhibitor or ARB Therapy
- For proteinuria >1 g/day: Initiate long-term ACE inhibitor or ARB with uptitration based on blood pressure 7, 1, 2
- For proteinuria 0.5-1 g/day: Consider ACE inhibitor or ARB therapy 7, 1, 2
- Titrate upward as tolerated to achieve proteinuria <1 g/day 7, 1
Blood Pressure Targets
Monitoring and Follow-Up
Short-Term Monitoring
- Check renal function and electrolytes within 1-2 weeks of starting ACE inhibitor or ARB 1, 3
- Monitor for hyperkalemia, a common side effect of renin-angiotensin system blockade 1, 3
Long-Term Monitoring
- Assess proteinuria, blood pressure, and eGFR every 3-6 months depending on severity 1, 3
- Evaluate risk of progression by monitoring these parameters at each visit 7, 1
Nephrology Referral Indications
- Proteinuria persists >1 g/day despite 3-6 months of optimized supportive care (ACE inhibitor/ARB and blood pressure control) 7, 1, 3
- Unexplained decline in kidney function 3
- Significant proteinuria with hematuria suggesting possible glomerular disease 1
Critical Pitfalls to Avoid
- Never treat asymptomatic bacteriuria except in pregnancy or before urologic procedures 1, 3
- Counsel patients to temporarily hold ACE inhibitors or ARBs during volume depletion or acute illness 1
- Do not initiate immunosuppressive therapy for proteinuria in patients with eGFR ≤30 ml/min/1.73 m² without nephrology consultation 7, 3
- Avoid high-dose corticosteroids or immunosuppression without kidney biopsy confirmation of the underlying glomerular disease 7