What is the initial workup for a patient presenting with proteinuria?

Initial Workup for Proteinuria

Begin with a spot urine albumin-to-creatinine ratio (ACR) or protein-to-creatinine ratio (PCR) on an early morning urine sample, confirm any positive result with a repeat quantitative measurement within 3 months, and assess eGFR and blood pressure at the time of diagnosis. 1, 2

Initial Detection and Quantification

Preferred Testing Methods (in order of preference):

• Urine albumin-to-creatinine ratio (ACR) on an early morning sample is the gold standard 1
• Urine protein-to-creatinine ratio (PCR) if ACR is unavailable 1
• Reagent strip urinalysis with automated reading (less preferred) 1
• Standard dipstick testing (least preferred for initial quantification) 1

Confirmation Strategy:

• If dipstick shows ≥1+ protein (roughly 30 mg/dL or PCR ≥300 mg/g), obtain a quantitative spot urine PCR 2
• Confirm any ACR ≥30 mg/g with a repeat early morning urine sample within 3 months 1
• Two or more positive quantitative tests spaced over 3 months confirms persistent proteinuria requiring further evaluation 1

Critical pitfall: Do not rely on 24-hour urine collections as the primary method—spot urine ratios are more convenient and equally accurate 1, 3

Essential Baseline Laboratory Assessment

Renal Function Evaluation:

• Serum creatinine with eGFR calculation using the 2009 CKD-EPI equation 1
• Report eGFR rounded to nearest whole number; values <60 ml/min/1.73 m² should be reported as "decreased" 1
• Consider cystatin C measurement if eGFR is 45-59 ml/min/1.73 m² without other markers of kidney damage to confirm CKD 1

Blood Pressure Measurement:

• Document blood pressure at initial presentation as it directly impacts risk stratification and treatment targets 1, 2

Diagnostic Workup to Identify Etiology

Serological Testing Panel:

• Hepatitis B and C serologies 2
• Complement levels (C3, C4) 2
• Antinuclear antibody (ANA) 2
• Quantitative immunoglobulins 2
• Serum and urine protein electrophoresis (to detect monoclonal proteins) 2
• Cryoglobulin levels 2

Imaging:

• Renal ultrasound to assess kidney size, rule out obstruction, and identify structural abnormalities 2
• Small kidneys (<9 cm length) suggest advanced irreversible disease 2

Specialized Urine Testing (when indicated):

• If non-albumin proteinuria is suspected, order specific assays for α1-microglobulin, monoclonal heavy or light chains (Bence Jones proteins) 1
• This is particularly important when PCR is elevated but ACR is relatively low, suggesting tubular proteinuria 4

Risk Stratification

Key Prognostic Factors to Document:

• Proteinuria level (most important predictor of progression) 1, 2
• Blood pressure (essential for treatment targets) 1
• eGFR (determines treatment eligibility) 1

Proteinuria >1 g/day indicates higher risk and necessitates more aggressive blood pressure targets (<125/75 mmHg) and mandatory ACE inhibitor or ARB therapy 1, 2

Common Pitfalls to Avoid

• False positives: Alkaline urine, concentrated urine, gross hematuria, mucus, semen, or white blood cells can cause false-positive dipstick results 3
• Benign causes to exclude: Fever, intense exercise, dehydration, emotional stress, and acute illness can cause transient proteinuria 3
• Don't use the term "microalbuminuria"—laboratories should report actual ACR values 1
• Understand that small fluctuations in eGFR are common and not necessarily indicative of progression 1

Follow-up Monitoring

• Assess eGFR and proteinuria at least annually in all patients with confirmed CKD 1
• More frequent monitoring (every 3-6 months) for patients at higher risk of progression or when measurements impact therapeutic decisions 1