What are the next steps for a patient with proteinuria (1+ protein in urine)?

Management of 1+ Proteinuria on Urinalysis

Confirm this proteinuria with quantitative testing using a spot urine protein-to-creatinine ratio (UPCR) or albumin-to-creatinine ratio (ACR) from a first morning void specimen before pursuing any further evaluation or treatment. 1, 2

Immediate Next Steps

Exclude Transient Causes First

• Do not proceed with extensive workup until you rule out benign, reversible causes that can temporarily elevate urinary protein 2:
  • Check for urinary tract infection (treat if present and retest after resolution) 2
  • Ensure no vigorous exercise within 24 hours before specimen collection 2
  • Avoid collection during menses in women 2
  • Consider recent fever or orthostatic proteinuria 3, 4

Obtain Quantitative Confirmation

• Order a spot urine protein-to-creatinine ratio (UPCR) on a first morning void specimen as the preferred confirmatory test 1, 2:

  • Normal: <200 mg/g (<0.2 mg/mg)
  • Abnormal: ≥200 mg/g
  • Alternatively, use albumin-to-creatinine ratio (ACR) with cutoff >30 mg/g 1

• A single dipstick reading of 1+ protein is insufficient for diagnosis and requires quantitative confirmation, as dipstick results can be affected by urine concentration 1, 2

Confirm Persistence

• Repeat quantitative testing within 3 months to confirm persistence 1:
  • Two or more positive quantitative tests spaced over 3 months = persistent proteinuria
  • If proteinuria disappears on repeat testing, this represents transient proteinuria (benign, requires no further evaluation) 3, 4

Risk Stratification Based on Quantitative Results

If UPCR <1000 mg/g (or <1 g/day)

• Initiate conservative management with ACE inhibitor or ARB therapy if proteinuria is between 500-1000 mg/day 1, 2:
  • Target blood pressure <130/80 mmHg 5
  • Add sodium restriction and optimize any underlying conditions (diabetes, hypertension) 2
  • Monitor for 3-6 months before considering further intervention 1, 2

If UPCR ≥1000 mg/g (≥1 g/day)

• Refer to nephrology for evaluation 2, 6:
  • This level warrants specialist assessment regardless of other findings
  • Likely represents glomerular disease requiring further workup 2

If UPCR >3500 mg/g (>3.5 g/day - Nephrotic Range)

• Immediate nephrology referral is mandatory 2:
  • High-risk for progressive kidney disease and cardiovascular events
  • Requires urgent specialist evaluation and likely kidney biopsy

Additional Baseline Testing

Obtain these tests concurrently with quantitative proteinuria confirmation 1, 6:

• Serum creatinine with calculated eGFR (using Cockcroft-Gault or CKD-EPI equation) 1
• Urinalysis with microscopic examination to assess for 6:
  • Dysmorphic red blood cells or RBC casts (suggests glomerular disease)
  • White blood cells (suggests infection or interstitial disease)
  • Cellular casts
• Serum albumin if nephrotic-range proteinuria is suspected 2

Nephrology Referral Criteria

Refer to nephrology if any of the following are present 2, 6:

• Persistent proteinuria >1 g/day (UPCR ≥1000 mg/g) despite 3-6 months of conservative therapy
• eGFR <30 mL/min/1.73 m²
• Abrupt sustained decrease in eGFR >20% after excluding reversible causes
• Active urinary sediment with dysmorphic RBCs or RBC casts
• Proteinuria accompanied by hematuria
• Nephrotic syndrome (proteinuria >3.5 g/day with hypoalbuminemia, edema)

Common Pitfalls to Avoid

• Never rely on a single dipstick reading alone - urine concentration significantly affects dipstick results, and a concentrated urine can show 1+ protein with normal total protein excretion 1, 7
• Do not order a 24-hour urine collection - spot UPCR or ACR is preferred for convenience and equivalent accuracy 1
• Do not delay treatment of reversible causes - if UTI is present, treat it first and retest rather than pursuing expensive workup 2
• Do not assume all proteinuria is glomerular - proteinuria <2 g/day can represent tubulointerstitial or vascular disease 4, 8