What labs should be ordered for a patient with a history of proteinuria (protein in urine)?

Laboratory Workup for Patient with History of Proteinuria

Order a first morning urine albumin-to-creatinine ratio (ACR) as your initial test, followed by serum creatinine with eGFR calculation. 1

Initial Urine Testing

Obtain a spot urine albumin-to-creatinine ratio (ACR) from a first morning void specimen as the preferred initial test for proteinuria assessment. 1 This is the KDIGO guideline's first-choice recommendation over other methods. 1

• If ACR is unavailable, use urine protein-to-creatinine ratio (UPCR) as the second-line alternative. 1
• Avoid 24-hour urine collections—they are cumbersome, often inaccurate due to incomplete collection, and unnecessary for routine clinical practice. 1, 2
• First morning specimens are superior to random samples because they avoid confounding from orthostatic proteinuria and exercise. 1, 3

Confirmation Testing

If the initial ACR is ≥30 mg/g, confirm with a repeat first morning void specimen. 4 Proteinuria is considered persistent when 2 of 3 samples over 3 months show ACR ≥30 mg/g. 4

• Patients should avoid vigorous exercise for 24 hours before sample collection, as this can falsely elevate results. 1
• Other causes of false-positive results include fever, dehydration, acute illness, menstruation, and urinary tract infection. 4, 5

Kidney Function Assessment

Order serum creatinine with calculated eGFR using the CKD-EPI equation. 1 This should be done simultaneously with urine testing to assess overall kidney function.

• If eGFR is 45-59 ml/min/1.73 m² without other markers of kidney damage, consider adding serum cystatin C to confirm chronic kidney disease. 1
• eGFR <60 ml/min/1.73 m² indicates decreased kidney function and warrants closer monitoring. 1

Additional Laboratory Tests

Complete the initial workup with:

• Complete blood count to assess for anemia or other hematologic abnormalities. 1
• Serum albumin to evaluate for nephrotic-range proteinuria if ACR/UPCR is markedly elevated. 1
• Urinalysis with microscopy to look for hematuria, cellular casts, or other sediment abnormalities that suggest glomerular disease. 1, 5

When to Order Specialized Testing

If UPCR is ≥500 mg/g (or ACR equivalent), consider:

• Referral for kidney biopsy to determine the underlying cause, particularly if there is unexplained decline in eGFR. 4
• Testing for specific urine proteins (α1-microglobulin, monoclonal light chains/Bence Jones proteins) if non-albumin proteinuria is suspected. 1

Ongoing Monitoring Schedule

For confirmed proteinuria with CKD, monitor at least annually:

• Serum creatinine/eGFR 1
• Urine ACR or UPCR 1
• Complete blood count, serum albumin 1

For higher-risk patients or those with declining function, increase monitoring frequency to every 3 months. 1, 4

Critical Pitfalls to Avoid

• Do not rely on urine dipstick alone—it detects total protein but misses albumin-specific proteinuria and can give false positives with alkaline urine, gross hematuria, or presence of mucus/semen. 5
• Do not use the outdated term "microalbuminuria"—laboratories should report actual ACR values instead. 1
• Do not order 24-hour urine collections routinely—spot ACR/UPCR ratios are more convenient, equally accurate, and better for patient compliance. 1, 2
• Do not forget to confirm positive results—transient proteinuria from benign causes (fever, exercise, dehydration) is common and does not require extensive workup. 1, 5