What is the initial workup and treatment for a patient with proteinuria?

Workup for Proteinuria

Begin by quantifying proteinuria with a spot urine protein-to-creatinine ratio when dipstick shows ≥1+ protein, then assess renal function with serum creatinine and eGFR, followed by urinalysis with microscopy to evaluate for glomerular disease. 1, 2

Initial Quantification and Confirmation

• Obtain spot urine protein-to-creatinine ratio when dipstick shows ≥1+ protein (correlates to approximately 30 mg/dL or protein-to-creatinine ratio ≥300 mg/g) 1, 2
• Repeat testing to confirm persistence before extensive workup, as transient proteinuria from fever, exercise, dehydration, or acute illness requires no further evaluation 3, 4
• If proteinuria persists for >3 months, it meets criteria for chronic kidney disease and warrants comprehensive evaluation 1

Essential Laboratory Studies

First-Tier Tests

• Complete metabolic panel including electrolytes, BUN, creatinine, glucose, and albumin 1
• Serum creatinine and estimated GFR to establish baseline kidney function 1, 2
• Urinalysis with microscopic examination specifically looking for:
  • Red blood cells, white blood cells, and cellular casts (suggests glomerulonephritis) 1
  • Hematuria combined with proteinuria strongly indicates glomerular disease 1

Second-Tier Tests (Based on Clinical Context)

• Hepatitis B and C serology 1, 2
• HIV testing in high-risk populations (African Americans, diabetics, hypertensives, hepatitis C coinfection, HIV RNA ≥14,000 copies/mL or CD4+ <200 cells/mL) 2
• Complement levels (C3, C4) to evaluate for immune-mediated glomerular disease 1, 2
• Antinuclear antibody (ANA) to screen for lupus nephritis 1, 2
• Serum and urine protein electrophoresis with immunofixation if age >40 or suspecting paraproteinemia (multiple myeloma, amyloidosis) 1, 5

Imaging

• Renal ultrasound if evidence of chronic kidney disease exists, to assess:
  • Kidney size (small kidneys <9 cm suggest advanced irreversible disease) 1, 2
  • Presence of stones 1, 2
  • Structural abnormalities 1

Categorization by Severity

• Mild proteinuria (<0.5 g/day): May represent benign causes or early kidney disease 1
• Moderate proteinuria (0.5-1 g/day): More likely represents kidney disease; consider ACE inhibitor/ARB with target BP <130/80 mmHg 1, 2
• Significant proteinuria (>1 g/day): Strongly suggests glomerular disease; start ACE inhibitor/ARB with target BP <125/75 mmHg 1, 6, 2
• Nephrotic-range proteinuria (>3.5 g/day): Indicates nephrotic syndrome; requires nephrology referral 1

Indications for Nephrology Referral

• Proteinuria >1 g/day despite 3-6 months of optimized supportive care 1
• Proteinuria with hematuria and/or cellular casts (glomerulonephritis) 1
• Declining renal function (increasing creatinine or decreasing eGFR) 1
• Nephrotic syndrome (proteinuria >3.5 g/day, hypoalbuminemia, edema, hyperlipidemia) 1
• When initial workup is inconclusive with persistent proteinuria >1 g/day despite conservative management (consider kidney biopsy) 6

Common Pitfalls to Avoid

• False-positive dipstick results can occur with alkaline urine, dilute or concentrated urine, gross hematuria, or presence of mucus, semen, or white blood cells 3
• Don't perform extensive workup for transient proteinuria—confirm persistence first 1, 3
• Don't overlook medication dose adjustments in patients with reduced kidney function 1
• Don't forget to assess urine sediment—the combination of proteinuria with active sediment (RBCs, WBCs, casts) dramatically changes the differential diagnosis toward glomerulonephritis 1