Workup for Persistent Proteinuria
The initial workup for persistent proteinuria should include quantification of protein excretion with a 24-hour urine collection, assessment for glomerular vs. non-glomerular causes, and evaluation for systemic diseases, with a threshold of >1000 mg/day (1 g/day) warranting thorough evaluation or nephrology referral. 1
Initial Assessment
Quantification of Proteinuria
- Confirm persistent proteinuria with repeat testing (at least 2-3 properly collected specimens)
- Quantify with 24-hour urine collection when dipstick shows ≥1+ protein
- Alternative: Spot urine protein-to-creatinine ratio (more convenient than 24-hour collection)
Risk Stratification Based on Protein Level
- <500 mg/day: Lower risk, monitor
- 500-1000 mg/day: Consider evaluation, especially if persistent or increasing
1000 mg/day (1 g/day): Requires thorough evaluation or nephrology referral 1
Evaluation for Glomerular vs. Non-Glomerular Causes
Urinary Sediment Examination
- Look for dysmorphic RBCs (>80% suggests glomerular origin)
- Check for RBC casts (pathognomonic for glomerular bleeding)
- Evaluate for other cellular elements
Assess for Features Suggesting Glomerular Disease
- Significant proteinuria (>1 g/day)
- Presence of red cell casts
- Renal insufficiency
- Dysmorphic RBCs in urine 1
Evaluation for Secondary Causes
Laboratory Testing
- Complete blood count
- Comprehensive metabolic panel (including creatinine, BUN, electrolytes)
- Serum albumin
- Lipid profile
- Complement levels (C3, C4)
- Antinuclear antibody (ANA)
- Hepatitis B and C serology
- HIV testing
- Blood glucose/HbA1c
Additional Tests Based on Clinical Suspicion
- Serum and urine protein electrophoresis (if multiple myeloma suspected)
- Anti-PLA2R antibodies (if membranous nephropathy suspected) 1
- ANCA (if vasculitis suspected) 1
- Anti-GBM antibodies (if Goodpasture's syndrome suspected)
Imaging Studies
- Renal ultrasound to assess kidney size, echogenicity, and rule out obstruction
Kidney Biopsy Considerations
- Indicated for:
- Nephrotic range proteinuria (>3.5 g/day)
- Proteinuria with active urinary sediment
- Proteinuria with reduced GFR
- Proteinuria with systemic disease
- Unexplained persistent proteinuria >1 g/day despite conservative management
Special Considerations
Orthostatic Proteinuria
- Common in adolescents and young adults
- Confirm with split urine collection (supine vs. upright)
- Generally benign with excellent prognosis
Transient Proteinuria
- May occur with fever, exercise, stress, or dehydration
- Resolves when inciting factor is removed
- Requires no extensive evaluation if transient
Common Pitfalls to Avoid
- Failing to quantify proteinuria with 24-hour collection or protein-to-creatinine ratio
- Overlooking systemic diseases that can cause proteinuria
- Delaying nephrology referral for patients with significant proteinuria (>1 g/day)
- Not distinguishing between transient and persistent proteinuria
- Missing red cell casts or dysmorphic RBCs that suggest glomerular disease
By following this systematic approach to evaluating persistent proteinuria, clinicians can efficiently identify patients who require more intensive management or specialist referral, potentially preventing progression to more severe kidney disease.